Neuroscience & Biobehavioral Reviews Volume Issue 2013 (Doi 10.1016 - J.neubiorev.2013.04.004) OlazÃƒÂ¡Bal, D. Pereira, M. Agrati, D. Ferreira, A. Flem

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Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx
Contents lists available at SciVerse ScienceDirect
Neuroscience and Biobehavioral Reviews

journal homepage: www.elsevier.com/locate/neubiorev
1 Review
2 Flexibility and adaptation of the neural substrate that supports maternal

3 behavior in mammals
4 Q1 D. Olazábal a,∗ , M. Pereira b , D. Agrati c , A. Ferreira c , A.S. Fleming d , G. González-Mariscal e , F. Lévy f ,
5 A.B. Lucion g , J.I. Morrell b , M. Numan h , N. Uriarte i
6 Q2 a
Departamento de Fisiología, Facultad de Medicina, Universidad de la República, Avda. Gral. Flores 2125, CP 11800, Montevideo, Uruguay
b
7 Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, NJ, United States
c
8 Sección Fisiología y Nutrición, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
d
9 Department of Psychology, University of Toronto at Mississauga, Mississauga, ON, Canada
e
10 Centro de Investigación en Reproducción Animal, CINVESTAV-Universidad Autónoma de Tlaxcala, Tlaxcala, Mexico
f
11 INRA, UMR 7247, CNRS/Université F. Rabelais/IFCE, Nouzilly, France
g
12 Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
h
13 Department of Psychology, Boston College, Boston, MA, United States
i
14 Laboratorio de Neurociencias, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
15
16 a r t i c l e i n f o a b s t r a c t
17
18 Article history: Maternal behavior is species-specific and expressed under different physiological conditions, and con-
19 Received 17 March 2013 texts. It is the result of neural processes that support different forms (e.g. postpartum, cycling sensitized
20 Accepted 8 April 2013 and spontaneous maternal behavior) and modalities of mother–offspring interaction (e.g. maternal
21 interaction with altricial/precocious young; selective/non-selective bond). To understand how the brain
22 Keywords: adapts to and regulates maternal behavior in different species, and physiological and social conditions
23 Cortex
we propose new neural models to explain different forms of maternal expression (e.g. sensitized and
24 Dopamine
spontaneous maternal behavior) and the behavioral changes that occur across the postpartum period.
25 Flexibility
26 Maternal behavior
We emphasize the changing role of the medial preoptic area in the neural circuitry that supports maternal
27 Medial preoptic area behavior and the cortical regulation and adjustment of ongoing behavioral performance. Finally, we dis-
28 Mouse cuss how our accumulated knowledge about the psychobiology of mothering in animal models supports
29 Oxytocin the validity of animal studies to guide our understanding of human mothering and to improve human
30 Rabbit welfare and health.
31 Rat © 2013 Published by Elsevier Ltd.
32 Sheep
33 Voles
34 Weaning
35 Contents
36 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
37 2. Diversity and complexity of parental behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
38 2.1. Maternal behavior in parturient and naïve cycling animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
39 2.2. Parental behavior in species with altricial, precocial or intermediate young . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
40 2.3. Selective vs. non-selective maternal behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
41 3. Onset, maintenance, and offset of maternal behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
42 3.1. Onset . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
43 3.2. Maintenance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
44 3.3. Offset . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
45 4. Neural basis of maternal behavior: a comparative analysis of its flexibility and adaptability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
∗ Corresponding author. Tel.: +598 2924 3414x3531; fax: +598 2601 1211.
E-mail addresses: dolazabal@fmed.edu.uy, neurolazabal@hotmail.com (D. Olazábal), pereiram@andromeda.rutgers.edu (M. Pereira), dagrati@fcien.edu.uy (D. Agrati),
anna@fcien.edu.uy (A. Ferreira), alison.fleming@utoronto.ca (A.S. Fleming), gglezm@prodigy.net.mx (G. González-Mariscal), levy@tours.inra.fr (F. Lévy), alucion@ufrgs.br
(A.B. Lucion), jmorrell@andromeda.rutgers.edu (J.I. Morrell), michael.numan@bc.edu (M. Numan), natiuria@fcien.edu.uy (N. Uriarte).
0149-7634/$ – see front matter © 2013 Published by Elsevier Ltd.

http://dx.doi.org/10.1016/j.neubiorev.2013.04.004
Please cite this article in press as: Olazábal, D., et al., Flexibility and adaptation of the neural substrate that supports maternal behavior in
mammals. Neurosci. Biobehav. Rev. (2013), http://dx.doi.org/10.1016/j.neubiorev.2013.04.004
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4.1. Comparative analysis of the neural basis of postpartum maternal behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

4.1.1. Inhibitory and stimulatory pathways . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.1.2. Cortical modulation of maternal behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.1.3. OXT modulation of maternal behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.1.4. Neural basis of individual recognition of the young . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.1.5. Limitations of current neural models of maternal behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.2. Functional reorganization of the neural circuitry of maternal motivation across the postpartum period . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.3. Neural basis of sensitized and alloparental behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5. Animal studies and their implications for human health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.1. Similarities and differences found in rodents and human studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.1.1. Pregnancy changes in attachment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.1.2. Hormonal associations with mothering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.1.3. Salience of Infant cues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.1.4. Affect and post partum depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.1.5. Cognition and executive function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.2. Human genetic studies derived from animal research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
6. Conclusions and perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
46 1. Introduction in some species like prairie voles, California mice, or marmosets, 88
the father or other members of the family group assist the female 89
47 Parental behavior is very diverse and expressed in different in the care of the young (Numan and Insel, 2003). The major- 90
48 forms and modalities. It generally consists of a series of behav- ity of lactating mammals share many behavioral features; they 91
49 iors that contributes to the survival of the young by providing clean off the neonates and consume fetal membranes and amni- 92
50 food, warmth, shelter, protection from predators and conspecifics, otic fluids, are very interested and attracted to young, and respond 93
51 and appropriate stimulation. Lactating females are commonly maternally protecting and nurturing them. However, the specific 94
52 responsible for providing all these benefits but, depending on the behaviors exhibited and the pattern of mother–young interactions 95
53 reproductive strategy of each species, males and other family mem- varies across species, the developmental status of the neonate, and 96
54 bers can also contribute (Numan et al., 2006). Maternal behavior is other factors. 97
55 displayed by females in different hormonal states and physiolog-

56 ical conditions, and under different social contexts. Mothers also
57 need to adapt to the growth of their offspring, which requires dif-
2.1. Maternal behavior in parturient and naïve cycling animals 98
58 ferent attention and care depending on the sensory, nutritional,
59 and motor competence of the young. This flexible caregiving strat-
Parental motivation is very high at the time of parturition, when 99
60 egy displayed by mothers requires a highly motivated and flexible
females (and in some cases males) show immediate interest in the 100
61 brain. This review discusses how the brain adapts to and regulates
newborn. In most rodents and primates, the parents build a nest 101
62 maternal behavior in different species, and under different physio-
or find a refuge, transport or retrieve the newborns to the nest or 102
63 logical and social conditions. In the present manuscript we review
refuge, clean and lick them and adopt nursing postures (González- 103
64 the neural basis that supports the different forms and modali-
Mariscal and Poindron, 2002; Numan and Insel, 2003). In other 104
65 ties of maternal behavior, putting emphasis on the flexibility and
species (e.g. capybaras and ungulates) mothers do not retrieve, 105
66 adaptation of the system. In the first two sections we introduce
transport or crouch over the offspring, and maternal behavior is 106
67 the topics discussed in the review and summarize the diversity of
mostly expressed through nursing, licking, guarding, and call voca- 107
68 forms (parturient, cycling sensitized, and spontaneously maternal
lizations. These different maternal strategies have been associated 108
69 females) and modalities (precocial vs. altricial young; prolonged vs.
to the degree of physical development of the offspring, as will be 109
70 short/infrequent interactions, selective vs. non-selective bond) of
discussed later. 110
71 maternal behavior in the different species. The third section makes
Maternal behavior can also emerge under other physiologi- 111
72 a comparative analysis of the hormonal and sensory factors that
cal and social contexts. For instance, cycling female rats become 112
73 mediate the onset, maintenance and decline of maternal behav-
maternal after relatively long term period of continuous exposure 113
74 ior in the different species and physiological conditions. Section 4
to foster newborn (ranging from 2 to 10 days, depending on the 114
75 revises our current neural models, analyzes their advantages and
strain, age, experience, and sex, among other factors, Cosnier, 1963; 115
76 limitations, adapts those models to explain the quick pup-induced
Rosenblatt, 1967). This process, which leads to a pattern of behavior 116
77 onset of maternal behavior, and adds a temporal dimension to
very similar to that of the lactating mother, is often referred to as the 117
78 explain the decline in maternal responsiveness across postpartum.
pup-induction or sensitization of maternal behavior (Numan et al., 118
79 Finally in Section 5, we discuss the contribution of animal studies
2006). During that sensitization period, the animal generally over- 119
80 to the understanding of human mother–infant interactions with
comes an initial aversion to pups, then tolerates them, and finally 120
81 potential applications to human welfare and health. In the last sec-
becomes attracted to them, leading to the display of all compo- 121
82 tion we summarize the main new concepts that have come out of
nents of maternal behavior. However, some non-parturient rodents 122
83 this review and raise some of the future challenges for the maternal
and primates readily interact with newborns, displaying immediate 123
84 behavior field.
maternal or paternal behavior without requiring long-term expo- 124
sure to infants. For example, most female and male prairie voles 125
85 2. Diversity and complexity of parental behavior when first exposed to newborns, retrieve and lick them, adopt nurs- 126
ing postures and build a nest (Olazábal and Young, 2005). Mice have 127
86 Parental behavior is very diverse among mammals. Mothers are also been reported to display maternal behavior rapidly (30 min–2 128
87 most commonly responsible for taking care of the offspring but, days), although not all the components of maternal behavior are 129
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130 always observed immediately (Kuroda et al., 2011; Lucas et al., Jaynes, 1956; Pereira, 2006). However, care of the offspring is some- 192
131 1998). times associated with a substantial cost to the mother because 193
132 Studies in eusocial rodents (naked mole rats) also show that sub- postnatal investment in developing young through lactation up 194
133 ordinate males and females with suppressed reproductive activity to weaning can reduce her opportunity to produce additional off- 195
134 contribute with the care of the offspring (Kalamatianos et al., spring. Therefore, in some species natural selection has favored 196
135 2010). Cooperative breeding, or the presence of non-breeding the evolution of mechanisms to ensure that the offspring of a 197
136 helpers within social groups, occurs in 30% of rodent families, in caregiver are the only beneficiaries of such parental investment. 198
137 many Canidae and in primates (e.g. marmosets, cappuchins). These This is common in species in which the young can be mixed, as 199
138 helpers assist in rearing offspring through activities such as feed- occurs in a variety of gregarious mammals with precocial young 200
139 ing, carrying, babysitting, and infant thermoregulation. In these (Poindron et al., 2007). Mothers of some of these species develop 201
140 cooperative breeding/rearing systems, helpers do not need a long selective maternal care, favoring their own young and rejecting 202
141 sensitization period and they quickly get involved in the care of any other young that are not theirs (e.g. sheep and goats). In these 203
142 the young. In humans, maternal behavior can also be expressed in cases the young also often recognize their mother (Nowak et al., 204
143 non-reproductive contexts, as shown by baby-sitters and other care 2011). However, in other group-living species (e.g. bats, capy- 205
144 providers (i.e. grandmothers), or mother substitutes when parents baras, water buffalo), mothers do not develop strong selectivity 206
145 are not available (Hrdy, 2008). and will take care of, or nurse, young belonging to other moth- 207
ers. Therefore, communal breeding systems can be an alternative to 208
146 2.2. Parental behavior in species with altricial, precocial or maternal selectivity for resolving this investment conflict in certain 209
147 intermediate young group-living species (Kerth, 2008; Macdonald et al., 2007). Extreme 210
cases of non-selectivity, and interspecific adoption in group-living 211
148 Altricial young are very immature at birth; hairless, with closed species have been observed in a population of capuchin monkeys 212
149 eyes, limited locomotor ability, and unable to regulate body tem- that adopted a marmoset young (Izar et al., 2006). 213
150 perature. After the mother has selected a site to build a nest, she
151 usually gives birth to numerous young (González-Mariscal and
152 Poindron, 2002; Numan et al., 2006). The site of the nest can be 3. Onset, maintenance, and offset of maternal behavior 214
153 underground, as in many rodents and in rabbits, or at ground level,

154 as among carnivores, or in trees, as in squirrels and prosimians 3.1. Onset 215
Q3 (Denenberg et al., 1969; González-Mariscal and Rosenblatt, 1996;

155
156 Kapeller, 1998). Mothers nurse their young in the nest and stimu- How does a cycling female become a mother? Are the hormones 216
157 late them to urinate or defecate by licking their ano-genital area. In of pregnancy necessarily involved in this transition? Experimen- 217
158 many species, they also retrieve them back to the nest. Marsupials tal approaches to these fundamental questions have revealed that 218
159 are an extreme case in this group as their young are very altricial some common mechanisms exist across mammals to promote 219
160 and initially carried by their mothers at all times. The embryonic the expression of maternal behavior. However, the diversity and 220
161 young crawl at birth into the mother’s pouch until they emerge as complexity of forms of maternal behavior also show significant 221
162 fully-developed, mobile animals (Kimble, 1997). differences and species-specific mechanisms. 222
163 In contrast, precocial newborns have completely functional Some of the behavioral components typically displayed by 223
164 hearing and vision at birth, rapid locomotive development, and mothers begin at the end of pregnancy, like the preference for 224
165 good thermoregulation. The young stand up and start suckling pup odors in rats (Bauer, 1983; Fleming et al., 1989; Kinsley and 225
166 within minutes of being born. Mothers can eventually lead their Bridges, 1990), rabbits (González-Mariscal and Chirino, 2011), and 226
167 offspring, or be followed by them, as the mother moves with her sheep (Lévy et al., 1983). The odors of newborn rats placed in 227
168 conspecifics in a herd (“leading-following” pattern of behavior dis- bed soil are strongly attractive for pregnant or cesarean delivered 228
169 played by sheep and horses). Follower species are usually herd primiparous rats (Kinsley and Bridges, 1990), even without any 229
170 animals (Lévy and Keller, 2008). In other species, the pattern of interaction with the young. In addition, the olfactory information 230
171 behavioral interaction is adapted to protect the young from preda- in the amniotic fluid that covers the lamb is highly attractive for 231
172 tors while mothers are foraging. That is the case of “hider” species, the ewes at parturition, before the delivery or interaction with the 232
173 in which the newborn stays hidden for several days, before starting lamb (Lévy et al., 1983). Human mothers are also attracted to infant 233
174 to follow its mother or grazing with her (e.g. goat, deer). During this odors and vocalizations (Fleming et al., 1993, 1997a,b; Stallings 234
175 hidden stage the mother returns periodically to feed her offspring et al., 2001), including mothers who had undergone delivery by 235
176 (Ralls et al., 1986). cesarean section, and had reduced or no experience with their 236
177 In other species (suids and many primates including humans), babies prior to testing (Porter et al., 1983). Therefore, the parturient 237
178 young at birth are semiprecocial or semialtricial. In those cases, animal does not need to learn or interact with the newborns to find 238
179 hearing and vision are functional, but neonates have poor loco- them attractive. Once the mother approaches and interacts with 239
180 motor and thermoregulatory autonomy. The number of neonates the young, other stimuli (e.g. tactile) strengthen maternal behavior. 240
181 varies from small (primates) to large (suids) litter. In primates, the After that, maternal behavior is maintained throughout lactation in 241
182 newborns are generally carried by their mother, father, or other the absence of the hormonal profile typical of the end of pregnancy. 242
183 members of the family group. Human mothers and other primates Estradiol (E2) and progesterone (P4) hormonal profiles stimu- 243
184 carry their infants in their arms, or transport them on their backs, late maternal behavior at the end of pregnancy in many species 244
185 side or chest (Nakamichi and Yanada, 2009). In suids, the mother (González-Mariscal et al., 1996; Numan et al., 2006). An increased 245
186 does not transport them and remains in a nest for the first two ratio of E2/P4 is associated with the onset of maternal behavior 246
187 weeks (Algers and Uvnäs-Moberg, 2007). in many species, including rats, rabbits, sheep, and some primates 247
(González-Mariscal and Poindron, 2002; Numan et al., 2006). How- 248
188 2.3. Selective vs. non-selective maternal behavior ever, there are some exceptions, as in hamsters that show a rise 249
in both E2 and P4 levels during pregnancy followed by a decline 250
189 In many species with altricial young (rodents in particular), after parturition without a change in E/P4 ratio (Numan et al., 251
190 mothers can recognize their own offspring but will take care of 2006). Yet, knocking out the gene for the E2 receptor-alpha (ERKO) 252
191 alien newborns, not establishing a selective attachment (Beach and increases infanticide (pup killing) and reduces retrieval in naïve 253
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254 cycling mice (Ogawa et al., 1998). In contrast, male P4 receptor the interaction (Bridges et al., 1974a; Mayer, 1983; Mayer and 320
255 knock out mice (P4RKO) are less infanticidal (Schneider et al., Rosenblatt, 1979). This suggests that there is an intrinsic maternal 321
256 2003). In addition, antagonists of the P4 receptor facilitate parental responsiveness that is inhibited in some species or at some ages 322
257 responses in naïve cycling mice while agonists increase infantici- or stages of the reproductive cycle of the individual. At parturition, 323
258 dal behavior (Schneider et al., 2003). Thus, ERKO and P4RKO studies this intrinsic maternal responsiveness is optimally stimulated by 324
259 in mice support the idea that an increase in the E2:P4 ratio and a hormonal changes to satisfy newborn needs. In the case of human 325
260 functional E2 receptor alpha are essential for the onset of maternal parental behavior, maternal responsiveness (reflected in attitudes 326
261 behavior while a role of the P4 receptor seems to differ between to the developing fetus) grows during pregnancy, peaks towards 327
262 male and female mice. the end of pregnancy and further develops across the early post- 328
263 Prolactin (PRL) and oxytocin (OXT) also facilitate the onset partum period with experience (Fleming et al., 1997a). 329
264 of maternal behavior in several species (Bridges, 1996). In early

265 studies, Bridges et al. (1985) showed that PRL administration in hor- 3.2. Maintenance 330
266 monally primed rats facilitated the induction of maternal behavior.

267 Later it was shown that central PRL or placental lactogen infusions The hormonal combinations present during pregnancy change 331
268 also facilitated maternal behavior in rats, and rabbits (Bridges and drastically around delivery and throughout lactation (for reviews 332
269 Freemark, 1995; González-Mariscal et al., 2004b). When the recep- see: González-Mariscal and Poindron, 2002; Numan et al., 2006). 333
270 tors for PRL were knocked out (PRLRKO), Lucas et al. (1998) found However, while hormonal changes related to parturition are impli- 334
271 that, compared to wild type virgin mice, the homozygous PRLRKO cated in the onset of maternal behavior, the maintenance of 335
272 naïve females had longer latencies to start showing all compo- maternal responses does not depend on the endocrine background 336
273 nents of maternal behavior (6 vs. 2 days). Central OXT infusions also of lactation. There is extensive evidence (Rosenblatt and Siegel, 337
274 facilitated maternal behavior in rats and sheep, while OXT recep- 1981) that around parturition, during which there is a heightened 338
275 tor (OXTR) antagonists delayed the onset of maternal behavior in sensitivity to the neonate’s signals, a transition from a hormonal 339
276 rats (Da Costa et al., 1996; Kendrick et al., 1987; Lévy et al., 1992; control to a somatosensory regulation of maternal behavior occurs. 340
277 Pedersen and Prange, 1979; Pedersen et al., 1985; van Leengoed The disruption of the mother–young contact at parturition (or the 341
Q4 et al., 1987, see also Section 6). Knock out models of the OXT sys-
278 immediate postpartum period) invariably provokes long-lasting 342
279 tem (including OXTR), however, have found no or minor deficits alterations in maternal behavior in rats, rabbits, and sheep, espe- 343
280 both in postpartum and in naïve pup-induced maternal behavior cially in primiparous females (for reviews see: González-Mariscal 344
281 (Macbeth et al., 2010; Nishimori et al., 1996; Pedersen et al., 2006; and Poindron, 2002; Numan et al., 2006). Thus, the expression of 345
282 Takayanagi et al., 2005). OXTKO or OXTRKO females, although maternal behavior is mostly maintained by the continuous stimu- 346
283 unable to nurse their young, show only minor deficits in retrieval lation coming from the young. Distal stimuli (visual, auditory, and 347
284 or licking behavior that recovered on subsequent testing days or olfactory) play an important role in the activation and orientation of 348
285 pregnancies. Perhaps, this minor effect is the result of the low mothers to the young, while proximal stimuli (taste, temperature 349
286 inhibition of maternal behavior that is typically present in virgin and skin texture) which are perceived in the physical interaction, 350
287 cycling female mice. However, Ragnauth et al. (2005) found higher are essential for the motor performance of active components such 351
288 infanticidal responses in OXTKO females when tested in a semi- as retrieving and licking in rats (Stern and Kolunie, 1989). Besides, 352
289 natural environment. Globally, transgenic models have shown that in this species, a threshold amount of suckling stimulation by the 353
290 these systems (E2, P4, PRL, and OXT) are more important during the pups is crucial for the adoption of the arched-back (kyphosis) nurs- 354
291 initial onset of maternal behavior, but not during the subsequent ing posture (Stern and Johnson, 1990). In sheep, recognition of the 355
292 postpartum maintenance of the behavior, especially in multiparous mother’s own lamb to allow suckling relies mostly on the learning 356
293 females. and subsequent perception of the lamb’s individual olfactory signa- 357
294 The mechanisms by which a female modifies her perception ture, although visual and acoustic signals also play a role (Lévy and 358
295 of pup odors, from unattractive (or aversive) when she is a vir- Keller, 2009; Nowak et al., 2011; Poindron and Le Neindre, 1980). 359
296 gin to attractive at parturition are still unknown. Daily exposure In rats a threshold amount of suckling stimulation is crucial for 360
297 to neonates provokes a gradual onset of maternal behavior in vir- the adoption of the arched-back (kyphosis) nursing posture (Stern 361
298 gin rats (Rosenblatt, 1967), but this manipulation is not effective in and Johnson, 1990). In rabbits, the temporal dimension of mater- 362
299 rabbits (Chirino et al., 2007; González-Mariscal et al., 2004a). Yet, in nal behavior is totally dependent on the characteristics of suckling 363
300 both species lesions to the main, or the accessory olfactory systems stimulation: various manipulations that reduce its amount alter 364
301 promote maternal behavior in virgins, especially under the action both the frequency of nursing (does enter the nest box more times 365
302 of estradiol (Chirino et al., 2007; Fleming and Rosenblatt, 1974a,b,c; than the usual one per day; González-Mariscal et al., 2011) and 366
303 González-Mariscal et al., 2004a). Anosmia can also induce maternal its duration (nursing bouts last longer than the usual three min; 367
304 behavior in non-pregnant sheep when combined with vaginocer- González-Mariscal, 2007; González-Mariscal et al., 2012). The qual- 368
305 vical stimulation (Poindron et al., 1988). Together these findings ity and quantity of the sensory stimulation received by the mother, 369
306 show that the maternal responsiveness of non-pregnant animals of changes as the newborn get older and independent, and this change 370
307 many species is under a tonic inhibition from the olfactory system might induce a reduction in maternal interest or motivation. 371
308 that must be removed across pregnancy to resolve, at parturi-

309 tion, the approach-withdrawal conflict of a cycling virgin female 3.3. Offset 372
310 towards the young.

311 However, in some other species (i.e. prairie voles and mice) Maternal behavior gradually declines across late lactation. As 373
312 this initial conflict is almost absent or resolved rapidly by naïve weaning approaches, some mothers avoid the suckling attempts of 374
313 cycling females. For instance, most naïve cycling female prairie the young, which also increase their time exploring and foraging 375
314 voles display retrieval behavior, licking, and crouching postures out of the nest and eating solid food (Cramer et al., 1990). These 376
315 over newborn (even toward newborn mice, D.E.Olazábal personal behavioral changes of the mother and the offspring eventually lead 377
316 observation) after only 15–90 s with them (Olazábal and Young, to the cessation of nursing (Cramer et al., 1990; Reisbick et al., 378
317 2005, 2006a). Juvenile rats (19–21 days of age) also show less 1975). The pattern and frequency of vocalizations of the mother 379
318 conflict when first exposed to newborns, displaying high levels and offspring, and other components of maternal behavior such 380
319 of contact and attractiveness toward pups from the beginning of as licking and grooming, are also reduced across the postpartum 381
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382 period in many species (Numan et al., 2006; Pereira and Morrell, PRL and OXT at the end of pregnancy act on the brain to stimulate 443
383 2009). In rodents, there is evidence that the main reasons why maternal responsiveness. Although other neurotransmitters and 444
384 mothers reduce maternal behavior across lactation are the changes peptides also participate in the regulation of the onset of maternal 445
385 in the stimuli coming from the growing litter: by continuously behavior (Bridges, 1996), in this review we have limited our discus- 446
386 replacing older pups with younger ones maternal behavior is pro- sion to a few systems. These hormones would act on their receptors 447
387 longed while doing the opposite procedure provokes a premature located in the medial preoptic area (mPOA), ventral portion of the 448
388 decline in nursing behavior (Bruce, 1961; Grosvenor and Mena, bed nucleus of the stria terminalis (vBST) and other areas of the 449
389 1974; Reisbick et al., 1975). However, other factors also appear to be brain, promoting the activation of brain pathways that stimulate 450
390 important. For example, the single, brief, daily nursing bout char- maternal responses, while suppressing pathways that inhibit them 451
391 acteristic of rabbits remains unchanged across lactation, despite (Bridges, 1996; González-Mariscal et al., 2005; Numan, 2006). 452
392 the fact that milk output decreases from around day 20 onwards
393 (González-Mariscal et al., 1994). The growing young play a minor 4.1.1. Inhibitory and stimulatory pathways 453
394 contribution to the termination of this component of maternal The classic neural models of maternal motivation and control of 454
395 behavior because doe rabbits continue to enter the nest box even maternal behavior are based on a significant amount of studies that 455
396 when milk production is minimal and the kits are already ingest- identified brain regions that, when monitored (in vivo microdialysis 456
397 ing solid food. However, if mated at post-partum estrus, rabbits and voltammetry analysis, immediate early genes activation, elec- 457
398 become concurrently pregnant and lactating; under these condi- trophysiological recordings, receptor up- or down-regulation, etc.) 458
399 tions, they stop nursing the “first” litter earlier than they do when or manipulated in different ways (lesions, chemical infusions, elec- 459
400 they are lactating only (Martínez-Gómez et al., 2004). On the other trical stimulation, temporary inactivation), were associated with 460
401 hand, pregnant lactating rats only reduce the time spent nursing the rather specific stimulation or inhibition of maternal behavior. How- 461
402 newborn near the second parturition (Rowland, 1981; Uriarte et al., ever, a challenge is to demonstrate that a subset of neurons, within 462
403 2008), but once the new litter is delivered the older juveniles are the monitored or manipulated brain regions, have a similar function 463
404 still nursed and cared for (Uriarte et al., 2008). Juvenile pups receive or form an ensemble, or neural network, specific to the motivation 464
405 even more maternal stimulation when a second litter of new- or control of the behavior of interest. Subsets of neurons within 465
406 born pups is present (Uriarte et al., 2008, 2009). Therefore, these those brain regions might share, or not share, electrophysiologi- 466
407 findings suggest that pregnancy-associated factors (hormonal and cal/chemical properties and connectivity and could play a role in 467
408 extra-hormonal) operate at the end of lactation in postpartum neural processes related to more than one behavior or motiva- 468
409 estrous-mated females to induce weaning in rabbits and to alter tion (see also Olazábal et al., submitted for publication-a,b). The 469
410 maternal behavior in rats. French et al. (2008) also found changes neural models proposed in the present review do not resolve this 470
411 in maternal behavior (less carrying behavior) associated to changes issue, but follow a previous strategy in the field that consists of 471
412 in the levels of androgens in marmoset pregnant mothers. focusing on identification of subregions of the brain associated 472
413 Although cessation of nursing is commonly associated with the with stimulatory or inhibitory functions of maternal behavior; with 473
414 end of maternal behavior in non-human animals, the maintenance the implicit view that these brain regions might be specifically 474
415 of a bond and association beyond nutritional weaning has not been engaged in maternal motivation and behavioral control. In order 475
416 investigated in detail. Suckling and mother–infant associations are to identify a subset of neurons within a brain region that might 476
417 maintained for a longer period of time than necessary from a nutri- specifically participate in the mediation of maternal behavior we 477
418 tional point of view in many species (Buckley, 2001; Cramer et al., need, at least, to use research tools that have good spatial reso- 478
419 1990; Hrdy, 2008; L’Heureux et al., 1995). lution. For this purpose, this review will pay particular attention 479
to the evidence obtained by using immediate early gene expres- 480
sion, associated with different parental behaviors and conditions. 481

420 4. Neural basis of maternal behavior: a comparative
Unfortunately, few electrophysiological studies have been done in 482
421 analysis of its flexibility and adaptability
the analysis of maternal behavior. Fos genes, commonly referred to 483
as immediate early genes, are activated in response to a variety 484

422 Considering the diversity of biological and physiological con-
of extracellular stimuli (e.g., hormones, neurotransmitters, neu- 485
423 texts under which parental behavior can be expressed, it is
romodulators). This activation produces several protein products 486
424 necessary to discuss the similarities and differences in the neu-
(c-Fos, Fos B, Fra-1, Fra-2) that serve as transcription factors that 487
425 ral mechanisms underlying the onset, maintenance, and decline
will alter target genes and their protein products, modifying the 488
426 of maternal responsiveness in different species and physiological
function of neurons (Sheng and Greenberg, 1990). Generally, Fos 489
427 contexts. Today, there is a disparity between our knowledge of
expression has been used as a neuronal marker of transcriptional 490
428 the neural basis of postpartum maternal behavior, compared to
activity, neuronal activity or engagement in response to certain 491
429 our understanding of paternal, sensitized or spontaneous parental
stimuli (González-Mariscal et al., 2009; Kalinichev et al., 2000b; 492
430 behavior. Studies in rats and sheep have contributed most to what
Numan et al., 2006). 493
431 we know about the neural basis of postpartum and hormonally-
The classic neural model of maternal motivation and control 494
432 induced maternal behavior (Lévy & Keller, 2008; Numan et al.,
proposes that the primary olfactory and the vomeronasal sys- 495
433 2006). Research in other species (González-Mariscal et al., 2009;
tems would be involved in the initial ofactory inhibitory process 496
434 de Jong et al., 2009, 2010; Katz et al., 1999) and MRI studies both in
observed in many species, in particular in rats and rabbits (see also 497
435 rodents and humans (Barrett et al., 2012; Nephew et al., 2009; Febo,
Section 3). This olfactory information is sent to the main (MOB) and 498
436 2011; Kim et al., 2011; Swain and Lorberbaum, 2008), support pre-
the accessory olfactory bulbs (AOB), then to the medial (MA) and 499
437 vious evidence collected in rat and sheep, but also add complexity
cortical amygdala (CA) and, from there, to the mPOA (to stimulate 500
438 to our understanding of the neurobiology of the parental brain.
maternal behavior), or the Anterior and Ventromedial Nucleus of 501
the Hypothalamus (AH/VMN) to inhibit maternal behavior in rats 502
439 4.1. Comparative analysis of the neural basis of postpartum (Bridges et al., 1999; Fleming et al., 1980; Numan, 2006; Numan 503
440 maternal behavior et al., 2006) and rabbits (Chirino et al., 2007; González-Mariscal 504
et al., 2004a; see also Fig. 1). Under the influence of hormones at 505
441 The classic view of the onset of maternal behavior in mammals the end of pregnancy, newborn-related stimuli would facilitate the 506
442 proposes that increases in E2/P4 ratio (see Section 2), and rises in activation of the pathway to the mPOA/vBST, and inhibit that to 507
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Fig. 1. The figure shows a hypothetical model for explaining the stimulation and inhibition of maternal behavior and its modulation by cortical areas and the mesolimbic
system. Olfactory inputs can either stimulate or inhibit maternal behavior depending on the physiological stage of the animal. The action of hormones at the end of pregnancy
stimulates different subregions of the medial and cortical Amygdala connecting to stimulatory (LSi-mPOAd/VBST-PAGl,vl; represented as light gray squares) or inhibitory
(AH/VMN-LSv-mPOAvl-PAGr; represented as dark gray squares) pathways. Areas of the brain represented as white ovals (MOB/AOB, MA/CA, VTA, NA, PFC, BLA, VP) participate
in the processing of stimuli that have a positive or a negative impact on maternal behavior. These brain regions might also have different subregions (still not identified)
specifically associated with attraction or aversion towards pups. All brain regions that appear in this figure have been shown to express oxytocin receptors in at least one
species. PVN likely projects to most of them. Note that the model is highly redundant (not all projections are shown) and that olfactory, visual, auditory and tactile information
that stimulates or inhibits maternal behavior is processed by different brain regions, likely modifying its weight in the model, depending on the sensory channel mostly used
by the different species. Lines ending in arrows signify excitatory projections, and those ending in a vertical bar are inhibitory.
508 the AH/VMN. In contrast, in non-maternal animals, the olfactory modulation of this brain region and its subregions by DA and 548
509 stimuli from pups would activate the AH/VMN, and subsequent OXT has not been studied in detail. The possibility that OXT and 549
510 areas associated to defensive and aversive responses (midbrain DA release in the LS during parturition or nursing contributes 550
511 periaqueductal gray, mPAG) such that escape, behavioral avoid- to removal of the inhibition of maternal behavior and defensive 551
512 ance, or attacks would occur. Note that the ventro lateral portion of responses by depressing vLS, while facilitating nursing via an action 552
513 the PAG (vlPAG) has also been implicated in the regulation of the on LSi is intriguing and deserves more investigation. 553
514 kyphosis (high-arched nursing) posture (Lonstein and Stern, 1998). Pup related stimuli processed by the hormonally primed brain 554
515 Therefore, the PAG is a complex neural region and while some of its can activate the mPOA and influence the NA (and other limbic 555
516 efferents may oppose maternal responsiveness, other PAG circuits and cortical regions) directly or indirectly through mPOA output 556
517 contribute to nursing behavior. to the VTA, thereby modifying the incentive salience of pup related 557
518 A more complex model of interaction among these brain regions stimuli and promoting maternal responses (Numan et al., 2006; 558
519 is proposed here and will be discussed in this section (see Fig. 1). The Numan and Stolzenberg, 2009; see also Olazábal et al., submitted 559
520 current anatomical, lesion, and immediate early gene activation for publication-a,b). Lesions or inactivation of the mPOA disrupt 560
521 studies have shown that different subregions of the mPOA (i.e. dor- retrieval, and in some cases also licking, nursing, and nest building 561
522 sal and ventrolateral), MA, and other areas of the brain could either in rats, and sheep (Numan et al., 1988; Pereira and Morrell, 2009; 562
523 stimulate or inhibit maternal behavior (Sheehan et al., 2000). Evi- Perrin et al., 2007), and also in male and female California mice (a 563
524 dence indicates that knowledge of a more detailed neuroanatomy biparental species, Lee and Brown, 2002, 2007). Lesions or inacti- 564
525 and neurochemistry underlying the functional connectivity of the vation of the NA fail to affect the active components of maternal 565
526 different brain subregions can enhance our understanding of the behavior in rats and mice (i.e. retrieval, Lee et al., 1999; Lee and 566
527 neural basis of maternal behavior (also see Sections 4.2 and 4.3). For Brown, 2007; Numan et al., 2005b). However, bilateral inactivation 567
528 example, different subregions of the lateral septum (LS) appear to of the ventral pallidum (VP) disrupts maternal behavior in rats, 568
529 promote either the inhibition or the activation of maternal behav- as does the unilateral inactivation of VP paired with a contralat- 569
530 ior. There is strong activation of the immediate early gene fos in eral depression of MPOA activity (Numan et al., 2005b). Therefore, 570
531 the ventral region of the LS (vLS) in non-maternal rats exposed to Numan’s model of the neural basis of the active components of 571
532 newborns. Thus, this area may be associated with the inhibition maternal behavior (Numan and Stolzenberg, 2009) proposes that 572
533 of maternal behavior in rats. However, c-Fos is also expressed in mPOA stimulation of VTA DA input to NA acts to suppress NA 573
Q5 the LS during parental behavior in voles (Kirkpatrick et al., 1994),

534 GABAergic inhibitory input to VP, allowing VP efferents to pro- 574
535 and rabbits (González-Mariscal et al., 2009), and in the intermedi- mote active maternal responses. Besides, the NA and the VP can also 575
Q6 ate portion of LS (LSi) in maternal rats (Sheehan et al., 2000, 2002).

536 adjust the ongoing behavioral performance projecting back to the 576
537 Also, lesions in the LS disrupt nursing and nest building in mice, rats mPOA via NA-mPOA or VP-medial thalamus-mPFC-NA projections 577
538 and rabbits (Cruz and Beyer, 1972; Fleischer and Slotnick, 1978; (Fig. 1). 578
539 Slotnick and Nigrosh, 1975), and increase infanticidal responses in The basolateral (BLA) and the central amygdala (CA) have also 579
540 mice and rats (Fleischer and Slotnick, 1978; Slotnick and Nigrosh, been implicated in the facilitation of maternal behavior processing 580
541 1975). This evidence suggests that different subregions of the LS of emotionally relevant information related to pups (Champagne 581
542 (vLS and LSi) might be engaged in the processing of pup related et al., 2001; Lee et al., 1999). Lesions or inactivation of the BLA, 582
543 stimuli under different motivational states. The LS also receives DA implicated in associative learning, mainly of emotional stimuli, 583
544 and OXT innervation in many species (including mice, rats, voles, disrupt maternal behavior in rats (Lee et al., 1999; Numan et al., 584
545 and rabbits), two systems well known for their mediation of mater- 2010) and mice (Lee and Brown, 2007), suggesting that this area 585
546 nal behavior (see also Olazábal et al., submitted for publication-a,b is critical for the processing of pup related stimuli that facilitate 586
547 and Sections 3.1 and 4.1.4). However, the specific neurochemical the expression of parental behavior and remembering previous 587
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Fig. 2. Hypothetical model of the changes in path weight and neural representations at early and late postpartum. Subpart A proposes an increased activity or engagement
of a subpopulation of neurons (mPOAd/vBST, big light gray square) that stimulate maternal behavior during early postpartum. This might be the consequence of the strong
influence of hormones of the end of pregnancy and the highly effective and frequent stimulation by the newborns. IL and Cg inputs are critical to maintain full maternal
behavior at this stage. Subpart B proposes increased activity or engagement of a subpopulation of neurons (mPOAvl, big dark gray square) that inhibit maternal behavior
during late postpartum. Changes in the function of the PL, and IL might be consequence of and adaptation due to the experience and learning of motherhood and the
characteristics of the near-weaning offspring. Lesions in these brain regions or in the mPOA would produce different effects at early or late postpartum (see also text in
Section 4.2). Abbreviations as in Fig. 1.
588 maternal experiences. The hormones of the end of pregnancy or the activates many cortical areas representing different sensory chan- 605
589 stimuli emitted by the young can then influence the BLA and the nels. Just recently, several authors have begun to pay attention 606
590 mPFC facilitating maternal behavior. This pathway might acquire again to the PFC and OFC in rats, and proposed that, via their pro- 607
591 significant importance after maternal learning and experience have jections to the mPOA and NA, these areas might be involved in 608
592 occurred, as in the late postpartum period (see Fig. 2 and Section the temporal organization of many of the maternal behavior com- 609
593 4.2). These brain regions also project to the mPOA and NA, modulat- ponents, and the regulation of attentional/motivational processes 610
594 ing mPOA-VTA-NA-VP information processing. However, the BLA related to maternal behavior (Afonso et al., 2007; Febo et al., 2008; 611
595 and CA can also be critical in fear and defensive responses toward Pereira and Morrell, 2011). 612
596 newborns (Bosch and Neumann, 2012; Wartella et al., 2003), and Early studies of Slotnick (1967) found that females with 613
597 therefore distinct population of neurons in these brain regions may PFC/cingulate lesions showed disorganized and persistent retrieval 614
598 play different roles (stimulation or inhibition) in maternal behavior. behavior. More recently, Afonso et al. (2007) also found that lesions 615
in this region altered the frequency, duration, and execution of 616
599 4.1.2. Cortical modulation of maternal behavior many maternal behavior sequences that require the coordination 617
600 The role of the cortex, in particular the PFC and orbitofrontal cor- of sensory and motor information in a spatial context (including 618
601 tex (OFC), in maternal behavior was mostly minimized or ignored retrieval behavior and licking). Maternal behavior can be adjusted 619
602 for a long time, with a few exceptions (Broad et al., 2002; Da Costa and organized by hippocampal, PFC, and amygdalar inputs to the 620
603 et al., 1997; Slotnick, 1967). Interestingly, Febo et al. (2008) found NA, modulated by DA projections from the VTA. Pereira and Morrell 621
604 that suckling and nursing provide a multisensorial experience that (2011, 2012) extended earlier findings (Afonso et al., 2007; Febo Q7 622
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623 et al., 2010), by demonstrating a specific necessary role for the and the behavioral processes that they control warrants future 688
624 infralimbic (IL) subregion of mPFC in early postpartum maternal investigations. Some evidence suggests that OXT may attenuate 689
625 behavior. Pereira and Morrell (2011, 2012) also found that, with the behavioral effects of psychostimulant drugs by interfering with 690
626 the progression of the postpartum period, the facilitatory role of mPFC glutamatergic projections to the NA (Qi et al., 2009). 691
627 the IL subregion wanes, whereas additional mPFC subregions, such

628 as the prelimbic (PrL), are recruited and contribute to the expres- 4.1.4. Neural basis of individual recognition of the young 692
629 sion of late postpartum maternal behavior (Pereira and Morrell, Finally, a major species difference lies in the development of 693
630 2011; see also Section 4.2). The importance of the mPFC in mothers selective care in mothers of some precocial species, which relies 694
631 planning, and cognitive flexibility has also been studied, and is still on a specific neural network different from the one involved in 695
632 more obvious in humans, and will be reviewed in more detail in maternal motivation. Mothers of some precocial species (sheep, 696
633 Section 5. goat) acquire the ability to recognize their own young soon after 697
birth, and refuse to nurse alien offspring (i.e. maternal selectiv- 698
634 4.1.3. OXT modulation of maternal behavior ity). In sheep and goats, such discrimination is established within 699
635 OXT function in maternal behavior has been extensively stud- 2–4 h after parturition and relies on olfaction. The neural sub- 700
636 ied and its interaction with the DA system might be informative strate controlling olfactory memory processes has been extensively 701
637 about the neural processes that support maternal motivation and studied in sheep and is thought to interact with brain regions reg- 702
638 behavior. The most likely role of DA in the regulation of maternal ulating maternal motivation to stimulate or inhibit it (Lévy and 703
639 behavior is discussed in Olazábal et al. (submitted for publication- Keller, 2008). Recognition of the young is mediated by the MOB 704
640 a,b). In this section we will discuss the role of OXT across species in which coding of the familiar lamb odor is established. Noradren- 705
641 and OXT/DA interaction. ergic inputs from the locus coeruleus to the olfactory bulb are in 706
642 OXT, released by the paraventricular nucleus of the hypothal- part responsible for the formation of this memory. Increases in 707
643 amus (PVN) at parturition, lactation, or during pup-interaction, noradrenaline release at parturition, with the help of OXT, cause 708
644 acts on the mPOA, VTA, PVN, and in some species on the NA (see the activation of cells in the olfactory bulb permitting potentiat- 709
645 Section 4.3), facilitating the quick onset of maternal behavior (Da ion of the glutamate system by the retrograde messenger, nitric 710
646 Costa et al., 1996; Fahrbach et al., 1984, 1986; Kendrick et al., oxide. This results in an enhanced cellular activity in response to 711
647 1987; Olazábal and Young, 2006a,b; Pedersen et al., 1994; Pedersen own-lamb odors. In this way, the output is decoded by subsequent 712
648 and Prange, 1979; van Leengoed et al., 1987) and maternal mem- olfactory processing regions. Among them, the CA and MA play 713
649 ory (D’cunha et al., 2011). In rats, the olfactory bulb is also a site a pre-eminent role (Keller et al., 2004b). Inactivation of either of 714
650 where OXT acts to facilitate the onset of maternal behavior (Yu these nuclei prevents mothers from learning to discriminate their 715
651 et al., 1996). In sheep, OXT modulates noradrenaline and acetyl- own from an alien lamb. The basal forebrain cholinergic system 716
652 choline release within the olfactory bulb, and infusions of OXT into is also activated at parturition and its lesion impairs the forma- 717
653 this area reduce aggressive behavior towards newborn lambs in tion of olfactory lamb recognition (Ferreira et al., 2001). How this 718
654 hormonally-primed ewes (Kendrick, 2000; Lévy et al., 1995). Neu- neural network is functionally interconnected with the one regu- 719
655 rons in the PVN are engaged (show c-fos activation), both during lating maternal motivation is currently unknown but a possible link 720
656 the first exposure to newborns and during early postpartum in rats between MA and the mPOA could be involved. 721
657 (Stack and Numan, 2000), rabbits (González-Mariscal et al., 2009),

658 and sheep (Keller et al., 2004a) and lesions in this brain region dis- 4.1.5. Limitations of current neural models of maternal behavior 722
659 rupt the onset of maternal behavior in rats, but not its maintenance Current models of maternal motivation propose that the brain 723
Q8 (Insel and Harbaugh, 1989; Numan and Corodimas, 1985). There

660 must be able to inhibit incompatible motivations in order to adapt 724
661 is important intra- and inter-specific variability in OXT receptors to complex and challenging situations (Numan, 2006, 2007). How- 725
662 (OXTR) that have been associated with natural variation in maternal ever, our models and paradigms of maternal motivation do not 726
663 behavior (Champagne et al., 2001; Olazábal and Young, 2006a,b). currently include mechanisms to coordinate several compatible 727
664 Interestingly, Champagne et al. (2001) found higher OXTR in the motivations and behaviors or switch among incompatible moti- 728
665 ventrolateral portion of the mPOA, an area previously suspected to vations to quickly adapt to a particular context (see also Olazábal 729
666 inhibit maternal behavior (Sheehan et al., 2000). OXT appears to et al., submitted for publication-a,b). Besides, until recently (Pereira 730
667 reach its target receptors via PVN projections, but also by diffusion and Morrell, 2011), our current models did not include a tempo- 731
668 (Landgraf and Neumann, 2004). It is intriguing, and still unknown, ral dimension that explains the dynamic of maternal responses 732
669 how OXT and DA systems interact in the VTA, NA, or other brain along lactation, and mostly focused on the onset and early main- 733
670 regions. Shahrokh et al. (2010) found that OXT infusions into the tenance of the maternal state (see Section 4.2). The quality of 734
671 VTA increased DA release in the NA, which, the authors propose, mother–offspring interactions, and frequency and type of contacts 735
672 would promote active behavior such as retrieval or licking (see vary in different species. The maternal brain should also be affected 736
673 also Olazábal et al., submitted for publication-a,b). In contrast, other in different ways by precocial or altricial young, accounting for dif- 737
674 authors (Kovacs et al., 1990; Qi et al., 2008) suggest that OXT acts to ferences in mother–offspring interactions. However, little is known 738
675 reduce the use of DA in the NA. In particular, OXT has been shown about the neural basis of mother–offspring interaction in hider 739
676 to attenuate hyperactivity and stereotyped behaviors induced by species, in particular the neural mechanisms that regulate their 740
677 psychostimulant drugs (Kovacs et al., 1990; Qi et al., 2008; Sarnyai encounters, as in rabbits. Besides, the neural basis and the dynam- 741
678 et al., 1991), and psychological dependence on such drugs (Qi et al., ics of regulation or control of mother–offspring interaction can be 742
679 2009; Yang et al., 2010). If OXT is released at high levels during expected to differ significantly in precocial vs. most altricial and 743
680 suckling and contact interaction with newborns, it should result in semi altricial species that are in contact with the offspring most of 744
681 the mother’s quietness and relaxation (typical of nursing) instead the time until weaning. 745
682 of invigorating the animal and activating motor components of the Another unexplored aspect of maternal behavior related to the 746
683 behavior (as expected with high DA in the NA). Our lack of infor- regulation of mother–offspring encounters is, for example, the 747
684 mation on the effects of OXT on the dopaminergic system in the vocalizations of the mother. These vocalizations play a critical role 748
685 different brain regions (NA, septum, mPFC, etc.) and how the dif- in the initiation of encounters in many species including deer, 749
686 ferent projecting pathways (from parvocellular vs. magnocellular sheep, and primates (Biben et al., 1989; Sèbe et al., 2008; Torriani 750
687 neurons) to these different regions regulate these target regions et al., 2006). However, the neural correlates of these vocalizations, 751
ARTICLE IN PRESS
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752 their motivational basis, and their changes across lactation have not maternal commitment of behavior, time and resources required for 816
753 been studied. What makes these mothers ‘call’ the young just once the care and protection of the altricial newborn pups. This series of 817
754 a day, or every 1 or two hours? Only newborn vocalizations (also studies provided important support for the role of cortical regions 818
755 critical for the orientation of the mother in her search) and their of higher-order cognition and polymodal sensory inputs in the 819
756 processing and recognition by the maternal brain, have been stud- expression of maternal behavior in rats. They found that the mPFC, 820
757 ied in rats, mice, ungulates, and humans (Blumberg and Alberts, and in particular the IL subregion, is critical for maternal behavior 821
758 1991; Cromwell, 2011; Harmon et al., 2008; Numan et al., 2006). in conflicting contexts, at which the animal must chose between a 822
759 Less attention has been paid to the neural regulation and function newborn and another salient stimulus (i.e. cocaine). 823
760 of mothers’ vocalizations when the offspring are at a distance. An As the postpartum period progresses and the pups grow older, 824
761 exception is the study by Perrin et al. (2007), which showed in sheep these authors found that the mPOA and the mPFC IL activity 825
762 a reduction in call vocalizations after inactivation of the mPOA. This changed, and additional network components, including the mPFC 826
763 finding is particularly interesting in the context of the discussion of PL subregion, were recruited with maternal experience, and con- 827
764 brain regions and neurochemical systems implicated in active and tributed to the expression of late postpartum maternal behavior 828
765 passive maternal motivation. Call vocalizations are part of a ‘seek- in rats (Pereira and Morrell, 2011). Specifically, they found that 829
766 ing’ system and they can include or not an important locomotor transient inactivation of the PL subregion of the PFC inhibited 830
767 component. In the Perrin et al. study, mPOA inactivation appeared late (but not early) postpartum maternal behavior. On the other 831
768 to reduce motorically active seeking (also called appetitive) and hand, transient inactivation of the mPOA, and IL blocked early 832
769 rather passive (vocalization calls) behavioral components that do (but not late) postpartum maternal behavior. Transient inactiva- 833
770 not require locomotor activity (see also Olazábal et al., submitted tion of the mPOA at late postpartum facilitated some components 834
771 for publication-a,b). The frequency and function of the vocalization of maternal behavior. In multiparous ewes, mPOA inactivation at 835
772 of the mother and the infant are also known to change as lactation parturition induced less deficit in maternal behavior than in primi- 836
773 proceeds in many species, including rodents and ungulates (Farrell parous mothers (Perrin et al., 2007). As discussed in Section 4.1 (also 837
774 and Alberts, 2002; Grimsley et al., 2011; Hiryu and Riquimaroux, see Numan et al., 2006), the mPOA appears to be a complex brain 838
775 2011; Motomura et al., 2002; Olazábal et al., unpublished; Sebe region with several subregions playing different (maybe opposite) 839
Q9 et al., 2008). Both mother and offspring frequency of vocalizations

776 functional and behavioral roles. Indeed, several studies have found 840
777 change in some ungulate species as the newborn get older and the evidence suggesting that neurons in the mPOA can be stimula- 841
778 dyad comes to recognize each other more easily through visual tory and inhibitory on maternal behavior (Olazábal and Morrell, 842
779 stimuli (Nowak et al., 2011; Olazábal et al., unpublished). The neu- 2005; Sheehan et al., 2000, 2002). Sheehan et al. (2000, 2002) 843
780 ral basis of these behavioral changes is still unknown. Species or found that the dorsal part of the mPOA (mPOAd) showed higher 844
781 periods at which the relevance of olfactory, visual, auditory, or c-fos activation in maternal, and the ventrolateral part (mPOAvl) 845
782 tactile stimuli changes, can inform us on how the brain adapts in non-maternal animals. Besides, a different temporal pattern of 846
783 to maintain maternal behavior by relying on different sources of Fos expression in the mPOA has been found in maternal animals of 847
784 information (see also Febo et al., 2008 for multimodal sensory rep- different species, contexts or physiological conditions that also sug- 848
785 resentations). gest adaptive processes in this brain region (see Section 4.3). Finally, 849
neurotoxic lesions in this area have also revealed atypical effects 850
786 4.2. Functional reorganization of the neural circuitry of maternal in juvenile and cycling maternal rats (Kalinichev et al., 2000a; 851
787 motivation across the postpartum period Olazábal et al., 2002). It is likely that hormonally- or experience- 852
mediated changes in the cortex and other brain regions not only 853
788 Maternal experience modifies the brain in such a way that the supplement but also change the mediation of maternal behavior 854
789 behavior is sustained during lactation and adjusted with little or by the mPOA (Febo et al., 2011; Pereira and Morrell, 2011). In addi- Q10855
790 no influence of gonadal hormones (see Section 3). As previously tion, maternal experience and hormones of the end of pregnancy 856
791 described (see Section 4.1), the mPOA is critical for the mainte- induce important plastic changes (e.g. increased brain-derived neu- 857
792 nance of maternal responsiveness in mice, rabbits, rats, sheep. rotrophic factor levels, neuron somal size, astocytic remodeling, 858
793 However, recent studies revealed that the role of the mPOA changes changes in dendritic arborizations) in the different components 859
794 across lactation according to maternal experience (Pereira and of the neural circuitry that supports maternal behavior, including 860
795 Morrell, 2011; Perrin et al., 2007). Even though postpartum females the mPOA, septum and PFC (Featherstone et al., 2000; Kinsley and 861
796 remain highly responsive to their young througout postpartum, Lambert, 2008; Kinsley et al., 2008; Salmaso et al., 2009; Shams 862
797 their maternal responsiveness undergoes considerable plasticity et al., 2012). 863
798 from birth to weaning, resulting in marked variations in mater- The fact that the mPOA is a key region implicated in the regu- 864
799 nal care attuned to the changing needs of the rapidly developing lation of active components of maternal behavior in most species, 865
800 young (Pereira and Morrell, 2009, 2011). contexts and physiological conditions, warrants future studies to 866
801 In a series of studies, Pereira and Morrell (2011) employed understand its anatomical, neurochemical, and functional com- 867
802 a transient site-specific neural inactivation method (infusion of plexity, and how this brain region stops promoting maternal 868
803 bupivacaine) to map the neural circuitry that subserves rat mater- behavior at weaning. The model shown in Fig. 2 needs more exper- 869
804 nal motivation across the postpartum period. Collectively, their imental support but reflects how interaction among brain regions 870
805 findings provided strong evidence that the ability of postpartum might change as the newborn grow older. This model is based on a 871
806 females to successfully care for their young is subserved by a dis- hypothesized change in the neural representation or neuroanato- 872
807 tributed neural network that carries out efficient and dynamic mical map in the mPOA and the different subregions of the mPFC 873
808 processing of complex, constantly changing incoming environmen- across the postpartum period. Similar changes can also be hypoth- 874
809 tal and pup-related stimuli, ultimately promoting the progression esized for other brain regions or pathways of the maternal neural 875
810 of appropriate care-giving behavior across the postpartum period. substrate. PFC-mPOA-VTA circuit may flexibly remap affective- 876
811 Specifically, these authors and others (Afonso et al., 2007; Slotnick generating functions as external situations change as proposed 877
812 and Nigrosh, 1975) found evidence that strongly suggests that by Reynolds and Berridge (2008) for NA. Note that the hypothe- Q11878
813 during the early postpartum period the integrated functional con- sized inhibitory role of the mPOAvl in maternal behavior must be 879
814 tribution of the mPOA, VTA, the infralimbic (IL) region of the taken with caution given that there is no study showing facilita- 880
815 mPFC, and other cortical subregions, is essential for the extensive tion of maternal behavior after lesions specifically located into this 881
ARTICLE IN PRESS
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Fig. 3. Hypothetical model to explain rapid or spontaneous parental responses. The abscence of an initial aversion or inhibition would promote a rapid engagement (or read
out) of the maternal pathway either by olfactory, auditory, visual, tactile or multimodal sensory inputs. Note that this model includes the lateral habenula (Lh) through which
most pup related stimuli can reach the VTA and NA. Because there is no inhibition to overcome, the mPOA might suffer less adaptational changes to stimulate maternal
behavior in these conditions.
882 subregion. However, inactivation in the whole mPOA might then and the activation of c-fos in weanling females differed from the 925
883 have different impact due to the weighed outputs to the VTA at early responses found in adults. Larger neurotoxic lesions of the mPOA 926
884 or late postpartum. At early postpartum, inactivation of the mPOA are needed to disrupt juvenile (20–25 days of age) maternal behav- 927
885 inhibits maternal behavior blocking the strengthened projections ior (Kalinichev et al., 2000a; Olazábal et al., 2002). Besides, in adult 928
886 from the dorsal part of the mPOA to the VTA that stimulate maternal sensitized or postpartum female rats, high expression of c-Fos is 929
887 behavior. At late postpartum, inactivation of the mPOA may have maintained in the mPOA after multiple exposures to pups, and at 930
888 facilitatory effects on maternal behavior by blocking the strength- least during 47 h of exposure (Stack and Numan, 2000). However, 931
889 ened projections from the MPOAvl to the VTA that stimulate the when juveniles are exposed to pups, mPOA Fos immunoreactivity 932
890 avoidance of the pups (Fig. 2). increases only during the first exposure, but not after subsequent 933
exposures when the animal is already maternal (Kalinichev et al., 934
891 4.3. Neural basis of sensitized and alloparental behavior 2000b; Olazábal and Morrell, 2005). Fos expression in the mPOA 935
in maternal juveniles is adult-like at around 25–29 days of age 936
892 Some primates (including humans), canids, and rodents species (Gonzalez and Fleming, 2002), interestingly associated with the 937
893 (including gerbils, mice, rats, voles) can eventually display parental beginning of an inhibitory behavioral response (neophobia) toward 938
894 responses without being pregnant, undergoing the hormonal newborns (Mayer, 1983). Although Fos expression to first pup 939
895 changes of the end of pregnancy, or receiving the sensory expe- exposure has generally been associated with brain regions that 940
896 rience typical of parturition and lactation. Studying sensitized inhibit maternal behavior (Olazábal and Morrell, 2005; Sheehan 941
897 maternal behavior and spontaneously parental species has the et al., 2000), that is not the only possible explanation. Transient 942
898 advantage of testing the neural substrate that regulates maternal Fos expression in the mPOA of spontaneously or rapidly-induced 943
899 behavior without the interventions of major hormonal changes, maternal females can still represent an egagement of this brain 944
900 something that also occurs in humans. In this section we will review region in the onset of maternal behavior. However, young juveniles 945
901 the neural basis of maternal behavior when this behavior occurs or spontaneously parental animals with less or no initial inhibi- 946
902 outside the postpartum reproductive period. A model of spon- tion may not longer need the neural adaptation that represents the 947
903 taneous or rapid pup induction of maternal responsiveness that continuous mPOA fos activation found in maternal sensitized or 948
904 assumes no or almost absent inhibition on maternal behavior is lactating adult rats. Transient expression of Fos in some area of the 949
905 shown in Fig. 3. brain (e.g. mPOA) might represent rapid adaptation of this region 950
906 Young male and female rats (20 days of age) can be induced in the processes that lead to the expression of maternal behavior 951
907 to display parental behavior very quickly (1 or 2 days, Bridges but, once the behavior is expressed, other brain regions (perhaps 952
908 et al., 1974b; Olazábal and Morrell, 2005), and voles do it in a few the lateral habenula) might also be recruited and fos activation (an 953
909 seconds or minutes (Olazábal and Young, 2006a,b; Roberts et al., the neural adaptation that it represents) not longer be needed in 954
910 1998). It is important to note that these young individuals display the mPOA. It is unlikely that the initial c-fos activation found in the 955
911 all the behavioral components that are present in lactating ani- mPOA in juvenile rats represents a subset of cells that inhibit mater- 956
912 mals (retrieval, crouching, licking, nest building), except for nursing nal behavior because weanling rats are attracted to pups from the 957
913 (Bridges et al., 1974a; Olazábal and Young, 2005). The presence of beginning. In addition, evidence in other species (prairie voles and 958
914 parental behavior in young weanling rodents, however, is not uni- california mice) also supports a different function for the mPOA in 959
915 versal. For example, weanling mice (20–22 days of age) rarely show the regulation of maternal behavior. Maternal and paternal prairie 960
916 parental responses after several days of exposure (Noirot, 1972). voles show c-Fos expression in the mPOA (Kirkpatrick et al., 1994; 961
917 The neural basis of these maternal responses of young animals Katz et al., 1999). However, this mPOA c-Fos expression occurs dur- 962
918 has been little studied. The mPOA, due to its critical role in adult ing the first 8 h of the interaction. After 24 h, the authors did not 963
919 postpartum maternal behavior, has been one of the most studied detect increased Fos immunoreactivity in the mPOA. The pattern of 964
920 brain regions. However, the role of the mPOA in the regulation Fos expression during the first exposure to newborns (that in voles 965
921 of weanling parental responses is still unclear (Kalinichev et al., results in parental behavior), agrees with the pattern of expres- 966
922 2000a,b; Olazábal et al., 2002). Although electrolytic lesions in sion of Fos in juvenile rats exposed to pups for the first time, or in 967
923 the mPOA can disrupt maternal behavior in 20–21 day-old juve- parental mice (increases in the mPOA, BNST, LS, PVN, among other 968
924 niles (Oxley and Fleming, 2000), the effect of neurotoxic lesions brain regions). Paternal mice also show increased Fos in the mPOA 969
ARTICLE IN PRESS
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970 (de Jong et al., 2009), but not in all experiments (de Jong et al., 2010). humans, as shown below. Many of our interpretations and studies 1033
971 When expressed, this mPOA Fos response declined from the first to that dealt with the complexity of the neural basis of maternal moti- 1034
972 the third day of pup exposure, as also seen in juvenile rats and adult vation need to adopt a similar philosophy. Maternal motivation 1035
973 voles. Lack of continuous activation of the mPOA in juvenile sen- needs to be adjusted to the real life and the challenges and changes 1036
974 sitized maternal females or spontaneously parental mice or voles that all species, including humans confront. The capacity of humans 1037
975 cannot be interpreted as the mPOA having no role in the mainte- to be flexible, break old habits and build new ones to enhance their 1038
976 nance of parental behavior in these species or conditions. However, adaptation to the needs and demands of infants is critical for a good 1039
977 it shows that the function of the mPOA can change among different parenting (Barrett and Fleming, 2011). Therefore, it is intriguing to 1040
978 species, social or physiological conditions. A decline in mPOA Fos compare the neural bases of animal and human parental motiva- 1041
979 expression was also found in postpartum ewes after a few hours tion and behavior: their flexibility, the role of learning, and patterns 1042
980 of interaction with the lamb (Keller et al., 2004a, 2005). Another of behavioral switching. These features are interesting considering 1043
981 example of species-specific function for maternal brain regions is MRI studies supporting a critical role for the animal and human cor- 1044
982 shown by lesions of the MA in voles and rats. While rats are neo- tex in maternal responsiveness and adaptation (Febo et al., 2001; Q121045
983 phobic and lesions in the MA facilitate maternal behavior, voles are Swain and Lorberbaum, 2008; Barrett and Fleming, 2011). Study- 1046
984 not (they even spontaneously take care of mice) and these lesions ing the same behavioral processes in different species will help us 1047
985 disrupt maternal behavior (Kirkpatrick et al., 1994). establish both the universality of some maternal processes as well 1048
986 Juvenile and spontaneously or rapidly induced maternal behav- as the important differences. This is particularly relevant in species 1049
987 iors have in common a low or absent initial inhibitory behavioral in which neural circuit differences can be hypothesized or predicted 1050
988 response. A brain region that is consistently activated during spon- based on different ecological needs and adaptations. 1051
989 taneous parental behavior in voles, and in California mice, or in the

990 rapid induction of parental behavior in weanling animals (also in 5.1. Similarities and differences found in rodents and human 1052
991 postpartum rats) is the lateral habenula (LHb). Lesions in the LHb studies 1053
992 disrupt maternal behavior in rats (Corodimas et al., 1993; Felton

993 et al., 1998). The LHb, which has neural connections with the mPOA, Much of what we know about the mechanisms regulating 1054
994 and the mesolimbic DA system (Bianco and Wilson, 2009; Hikosaka maternal behavior in mammals is derived from work on nonhuman 1055
995 et al., 2008), is positioned in an optimal place to regulate rapid mammals, especially rats, mice, voles, rabbits, sheep, and monkeys 1056
996 maternal behavioral responses (de Jong et al., 2010). Future stud- (Numan et al., 2006). Here we will briefly compare nonhuman 1057
997 ies should investigate its role in the induction of maternal behavior mammals (primarily rats) and humans in terms of the role of hor- 1058
998 in other species and conditions, and particularly its role in rapid mones, sensory stimulation, the brain, and genetics in mothering 1059
999 pup-induced parental responses. and in other behavioral systems relevant to mothering. 1060
1000 Finally, there is also strong correlational evidence (Kalamatianos Many cognitive functions are enhanced in the new mother as 1061
1001 et al., 2010; Olazábal and Young, 2006a,b; Schorscher-Petcu et al., compared to the nonmother or pregnant animal; new mothers are 1062
1002 2009), and a few pharmacological and genetic manipulations more attracted to young (Mattson et al., 2001), less fearful in general 1063
1003 that support the role of OXT in the NA in the quick stimula- (Hansen and Ferreira, 1986), and less avoidant of pups, specifically 1064
1004 tion of parental responses in weanlings (also in rats) and adult (Fleming and Luebke, 1981), more attentive (Lovic and Fleming, 1065
1005 voles (Keebaugh and Young, 2011; Olazábal and Young, 2006a,b; 2004), less impulsive (Lovic and Fleming, 2004), more suscepti- 1066
1006 Peterson et al., 1991). Therefore, considering the proposed model ble to effects of experience (Fleming and Korsmit, 1996), and more 1067
1007 of the neural basis of maternal behavior in the previous section (see able to learn about certain aspects of their environment, although 1068
1008 Fig. 1), the areas of the brain that support maternal behavior could they may in fact learn less about other domains (Love et al., 2005). 1069
1009 change their function or relevance to the maternal circuitry in dif- New mother rats are also less easily stressed by general stressors 1070
1010 ferent species or under different physiological contexts, where their (Tu et al., 2005; Neumann et al., 1998). These behavioral changes 1071
1011 connections can be strengthened or weakened. Investigation of the and adaptations postpartum contribute to a well orchestrated, 1072
1012 neural basis of spontaneous parental or infanticidal behavior can highly motivated pattern of maternal responding even after the 1073
1013 contribute to distinguishing inhibitory vs. stimulatory pathways or first parturition (see Barrett and Fleming, 2011). Associated with 1074
1014 brain regions associated with rapid pup-induced maternal behav- these changes there also occur changes in the animals’ endocrine 1075
1015 ior. How brain regions control the output of rapid or spontaneous state (see Section 3), neurotransmitter function (see Section 3 and 1076
1016 behavioral responses is a topic of research that needs to be further Olazábal et al., submitted for publication-a,b), patterns of brain acti- 1077
1017 developed (Fig. 3). vation and plasticity (Stack and Numan, 2002; Kinsley et al., 2008), Q131078
and epigenesis of some of the relevant receptor systems (Cameron 1079
et al., 2008). 1080
1018 5. Animal studies and their implications for human health Using the animal model as a guide, Fleming and colleagues have 1081
explored maternal sensitivity and mothering in human mothers 1082
1019 In this section we will address the validity of our experimental of newborns, on day 2 post-partum, and at 3 and 6 months post- 1083
1020 models and experimental strategies to understand human mater- partum. They have concentrated on the early postpartum period 1084
1021 nal motivation and behavior. Most experimental models used in when mothers in most cultures are still nursing their infants, and 1085
1022 the laboratory carefully consider the biology and the natural needs when the mother and infant are most exclusively in contact with 1086
1023 of the studied species, and all the maternal contexts and physio- one another. These studies focused on some of the cross-cultural 1087
1024 logical conditions discussed in this review have also been found similarities across mothering, while at the same time recognizing 1088
1025 in the wild. However, generalization of our findings in the lab to the huge differences that occur cross-culturally in styles of moth- 1089
1026 the life of the species in the wild is something that we cannot ering and societally-dictated socialization patterns. 1090
1027 always do because of the lack of information on the behavior of our

1028 experimental animals in the wild. The social and parental interac- 5.1.1. Pregnancy changes in attachment 1091
1029 tions in the wild are clearly more complex, and the environment Assessments of maternal feelings of nurturance across preg- 1092
1030 more unstable than in the lab. That difference suggests that animals nancy in women, determined through factor analyses of responses 1093
1031 that change their behavior and adapt to their environmental needs on maternal questionnaire items, show that these feelings develop 1094
1032 would survive in better conditions. This seems to be also valid in across pregnancy showing two periods of elevation from the 1095
ARTICLE IN PRESS
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1096 non-pregnant state or early pregnancy. The first period would be in the blues. Depression usually does not include elation but does 1159
1097 at the time of quickening, at the end of the first trimester and include anxiety, and negative mood or flat affect, fatigue and cog- 1160
1098 likely result from the internal movements of the infant and the nitive distortions (Letourneau et al., 2012). Although these early 1161
1099 recognition by the mother of the reality of the developing fetus post-partum phenomena are clearly associated with some of the 1162
1100 (Fleming et al., 1997a). The second period occurs close to parturition largest hormonal shifts in a woman’s life at the time of parturi- 1163
1101 and peaks immediately postpartum (Fleming et al., 1997a). These tion, surprisingly few studies have demonstrated a consistent and 1164
1102 changes are similar to the ‘pregnancy effect’ reported for pregnant robust hormonal mechanism. Candidate hormones have included 1165
1103 rats by Siegel and Rosenblatt (1975) but unlike the rat situation, in parturitional changes in P4, E2, cortisol, PRL, thyroid hormones, 1166
1104 humans, these changes seem to have a psychologic basis and are and serotonin (Barrett and Fleming, 2011). Although the nature 1167
1105 not related to the hormonal changes of pregnancy. of the parturitional affective change cannot be compared between 1168
rat and human, some change in affect occurs in both, and in both 1169
1106 5.1.2. Hormonal associations with mothering the mood change is related to responsiveness to infants. Moth- 1170
1107 An association has been found between mother’s feelings of nur- ers who are depressed are less responsive to their infants; they 1171
1108 turance on the first postpartum day and their earlier pregnancy are characterized as less sensitive, more easily irritated, and less 1172
1109 hormonal profile (Fleming et al., 1997a). In addition to the steroids contingent (Barrett and Fleming, 2011). These behavioral char- 1173
1110 (see Section 3), E2 and P4, other hormones have also been studied in acteristics clearly impact on the infant who, as a consequence, 1174
1111 human mothers. In a series of studies in new mothers, Fleming et al. also becomes less responsive and interactive (Letourneau et al., 1175
1112 (1997b) found that the adrenal hormone cortisol was positively 2012). 1176
1113 associated with higher levels of affectionate contact and attraction

1114 to infant odors. Later in the postpartum period, this relationship 5.1.5. Cognition and executive function 1177
1115 was reversed, where high cortisol was associated with more dys- Humans are also cognitive creatures and learn a lot from expe- 1178
1116 phoria, which in turn was associated with less interaction with the rience. Nowhere is this more apparent than with motherhood. 1179
1117 infant (Fleming et al., 1997b). Rat work by Rees et al. (2004) indi- There are very considerable differences between first time mothers 1180
1118 cates a similar role for corticosterone in rat dams. Finally, there is a and multiparous mothers indicating that maturity and experience 1181
1119 growing literature in humans showing that in the early postpartum together give the multiparous mothers additional knowledge and 1182
1120 period, there are also associations between OXT and measures of self-confidence. In fact, if one compares the first time mother 1183
1121 maternal behavior, which has been widely reported in the animal with the multiparous mother in responses to the recorded cries 1184
1122 work (Feldman et al., 2011; Nissen et al., 1998; Skrundz et al., 2011, of infants, the experienced mother responds predominantly to 1185
1123 also see Sections 3, 4 and 5.2). the pain cry of the infant whereas the new primiparous mother 1186
responds equally to the pain and hunger cries, indicating that they 1187
1124 5.1.3. Salience of Infant cues are not yet familiar with the meaning of the cry and so become 1188
1125 There are other interesting features of new mothers’ responses alerted to both (Stallings et al., 2001). 1189
1126 to their infants that we have encountered in the animal literature. Recent studies that explored executive function in new moth- 1190
1127 New mothers find infant body odors to be more attractive than do ers support the evidence found in the rat by Lovic and Fleming 1191
1128 nonmothers. Presentation of other non-baby odors (spice, cheeses, (2004). These authors found a negative relationship between errors 1192
1129 etc.), do not produce the same differential response. Mothers were in attention set-shifting, and elevated impulsivity, and amount 1193
1130 tested ‘blindly’ and they were all unaware of the source of the odor- of maternal licking in rats. Maternal rats that were less atten- 1194
1131 ants. Hence, infant odors are particularly salient to the new mother; tive in attention tasks were also less attentive to their offspring. 1195
1132 but as in rats that attraction is increased by experience. Mothers In a recent series of studies González-Mariscal et al. (2012), and 1196
1133 with more experience interacting with their infants on the first Deater-Deckard et al. (2012) reported very similar findings in 1197
1134 days of life give more positive ratings (Fleming et al., 1993). They human mothers. Postpartum mothers and mothers of 3–7 years 1198
1135 also are better able to recognize their own infant based on their old children who had problems with executive function tasks, 1199
1136 odors, when presented with two containers, one containing own whether attention set-shifting, or spatial working memory, were 1200
1137 infant t-shirt; the other a same aged and gendered other-infant t- less sensitive mothers (González-Mariscal et al., 2012), or less 1201
1138 shirt. Again, this early recognition and learning about the odors of capable of minimizing the effects of harsh parenting (Deater- 1202
1139 their own infants involves quite rapid learning, similar to what has Deckard et al., 2012). This is particularly true of teenage mothers 1203
1140 been described in sheep, albeit less exclusively so (Lévy and Keller, who, as a group, have the most problem with the planning, 1204
1141 2008; Nowak et al., 2011). Interestingly, again the hormone corti- organization, attention, and flexibility, and also are well known 1205
1142 sol seems to be the hormone most associated with these hedonic to have more problems interacting sensitively with their babies 1206
1143 responses (Fleming et al., 1997b). New mothers are also partic- (Giardino et al., 2008). Despite these clear associations between 1207
1144 ularly sympathetic to the sounds of infant cries, showing heart executive function and mothering, we still do not have a good 1208
1145 rate accelerations and cortisol responses that are not seen in non- handle on whether new mothers differ from non-mothers in 1209
1146 mothers (Fleming et al., 1997b; Stallings et al., 2001). In this case, their executive function. However, it seems clear that appropri- 1210
1147 the salience of the cry stimuli elicits not only mothers expressed ate flexibility to adapt to the new situation and the changing 1211
1148 sympathy but is also associated with a pattern of cortisol response baby is advantageous for mothers. We do know, however, that 1212
1149 that seems to be associated with alertness and arousal in the new in fMRI studies of maternal responses to infant cues, the areas of 1213
1150 mother. the brain most activated in response to pictures of own infants 1214
are regions and circuits important for animal maternal behavior, 1215
1151 5.1.4. Affect and post partum depression including the amygdala, the striatum, and the PFC, regions well- 1216
1152 It is well known that new mothers are also quite moody, with known to be implicated in the regulation of emotion, reward, 1217
1153 50–70% experiencing postpartum blues during the first postpar- attention, and executive function (Barrett and Fleming, 2011). 1218
1154 tum weeks and 15–20% experiencing more severe depression that The similarities found in animal and human studies show that to 1219
1155 extends into months (Letourneau et al., 2012). In general, blues is understand mothering it is important to understand the psycho- 1220
1156 characterized by lability and one of its primary features is where logical components that make up mothering, including mothers’ 1221
1157 mothers feel both elated and tearful alternately and even simulta- perception, affect and cognition, and their physiological corre- 1222
1158 neously (Buttner et al., 2012). Anxiety, as well, figures prominently lates. 1223
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1224 5.2. Human genetic studies derived from animal research (dopamine D4 receptor, catechol-Omethyltransferase, dopamine 1289
transporter) have been associated with different forms of parenting 1290
1225 An interesting approach that is also extensively used today, con- and parental responses to infant’s behavior (Kaitz et al., 2010; and 1291
1226 sists in investigating the interaction between gene variants and Lee et al., 2010; van Ijzendoorn et al., 2008). The main finding of 1292
1227 the environment and family context of parents. A genetic polymor- van Ijzendoorn et al. (2008) was differential susceptibility to has- 1293
1228 phism consists of a difference in DNA sequence among individuals. sles depending on the gene variants of the dopaminergic system 1294
1229 Single Nucleotide Polymorphisms (SNP) are the most common type found in parents. When parents had a DRD4-7R (7-repeat DRD4 1295
1230 of genetic variation in the human genome, and occur when sin- allele) as well as a COMT val allele, they displayed less sensitive 1296
1231 gle nucleotides in the genome differ among individuals, groups or behavior to the attachment needs of their children when they had 1297
1232 populations. SNPs can be present in non-coding or coding regions to deal with more daily hassles. However, they were more sen- 1298
1233 and are commonly associated with different phenotypes (includ- sitive when they experienced few daily hassles, suggesting that 1299
1234 ing diseases). For example, several gene polymorphisms have been the combination of SNPs implied increased susceptibility to daily 1300
1235 associated with many healthy and pathologic behaviors in humans stresses in parents. Later, Kaitz et al. (2010) found that mothers with 1301
1236 (Chen et al., 2011; Costa et al., 2009; Walum et al., 2012). A recent the DRD47R allele responded more sensitively to infants that were 1302
1237 series of studies that investigated several genetic polymorphisms fussier and less sensitively to infants who were less fussy, suggest- 1303
1238 in the oxytocinergic and dopaminergic systems in human moth- ing DRD47R was associated with increased susceptibility to context 1304
1239 ers conforms with the data from animal studies (see Section 3 (Kaitz et al., 2010). These authors propose that the presence of a 1305
1240 and Olazábal et al., submitted for publication-a,b). Associations DRD4 7-repeat allele predicts better performance in more arous- 1306
1241 between OXT and different aspects of maternal behavior and social ing or challenging contexts and poorer outcome in less arousing 1307
1242 interaction with infants has been found in humans (Bakermans- or challenging contexts. Lee et al. (2010) also found an associa- 1308
1243 Kranenburg et al., 2012; Bick and Dozier, 2010; Skrundz et al., 2011; tion between a variant in the gene of the dopamine transporter 1309
1244 Strathearn et al., 2009). Strathearn et al. (2009) found higher serum (DAT1 genotype) of the mother and negative parenting. This asso- 1310
1245 OXT response to infant contact at 7 months in secure compared to ciation was significantly stronger in mothers whose children were 1311
1246 insecure mothers. Human mothers who presented increased levels very disruptive during the mother–child interaction task, sugges- 1312
1247 of affectionate contact demonstrated an OXT increase subsequent tive of a gene–environment interaction. In a more recent study, 1313
1248 to the mother–infant interaction (Feldman et al., 2007, 2011). How- Mileva-Seitz et al. (2012) asked how individual haplotypes (a set 1314
1249 ever, results by Bick and Dozier (2010) suggest the nurturance-OXT of SNPs that tend to be inherited together, possibly because the 1315
1250 relation may not be so clear-cut; these authors found that urine SNPs are located within a single chromosome) of the DRD1 and 1316
1251 OXT was in fact higher when mothers were interacting with unfa- DRD2 genes related to different measures of mothering. Consistent 1317
1252 miliar compared to their own children. Finally, low plasma OXT with predictions from the animal work, they showed that genetic 1318
1253 levels during mid-pregnancy predicted symptons of postpartum variation in both DRD1 and DRD2 genes in human mothers pre- 1319
1254 depression 2 weeks following birth (Skrundz et al., 2011). Skrundz dicted variation in specific maternal behaviors during a 30-min 1320
1255 et al. (2011) propose that OXT is implicated in stimulating mother’s mother–infant interaction at 6 months postpartum. DRD1 SNPs and 1321
1256 well-being and reducing anxiety during mother–offspring inter- haplotypes were significantly associated with maternal orienting 1322
Q14 action. Bakermans et al. (2008) looked to a variant of the OXTR

1257 away from the infant, while DRD2 haplotypes were significantly 1323
1258 gene and found a polymorphism (rs53576) related to lower levels associated with maternal vocalizing/speech to the infant. Taken 1324
1259 of sensitive parenting. More recently, Feldman et al. (2012) found together these gene polymorphism studies suggest that different 1325
1260 that OXTR polymorphic variants (rs2254298 and rs1042778) were gene groups may be associated with different maternal phenotypes 1326
1261 associated with lower plasma OXT and less parental touch. Finally, and that the environment can moderate genotype-behavior associ- 1327
1262 in a recently completed study Mileva-Seitz et al. (unpublished) ations to different extents for these different maternal phenotypes. 1328
1263 explored the associations of early experience and mothering and They also highlight the importance of analyzing different compo- 1329
1264 the moderating effects of OXT genotypes on that relation. The study nents of mothering and pay attention to its multidimensionality. 1330
1265 examined associations between polymorphisms in OXT and OXTR Alltogether these studies support a role for OXT and DA systems 1331
1266 in a sample of 187 Caucasian mothers at six months postpartum genes in human maternal motivation. One of the main conclusions 1332
1267 and found that two separate OXT SNPs (rs2740210 and rs4813627) from these genetic studies is the importance of the context and 1333
1268 significantly associated with maternal-infant directed vocalizing of the dynamics of mother–child interactions in studies on human 1334
1269 regardless of early maternal environment. They also found a signif- parental behavior. Polymorphisms for other hormonal receptors 1335
1270 icant genotype-environment interaction between these two SNPs systems such as ERalpha, and P4 receptors, or PRLR have not been 1336
1271 and maternal early life experiences, on maternal instrumental investigated in relation to variations in human or animal parental 1337
1272 grooming, and on maternal postpartum depression. Although it behavior. 1338
1273 is currently not known how these OXTR and OXT polymorphisms
1274 relate to OXTR density and OXT levels (in the brain or other organs),
1275 respectively, these are promising studies when included within a 6. Conclusions and perspective 1339
1276 family, experience, and contextual background.

1277 Despite the substantial evidence implicating the dopaminer- The rich exchange of ideas among the participants of the present 1340
1278 gic system in maternal motivation (Olazábal et al., submitted for review has led to a revised neural model of parental behavior and 1341
1279 publication-a,b), few studies have focused on DA facilitation of has also revealed unexplored aspects related to the neural basis of 1342
1280 maternal behavior using knockout mice. The only exception is maternal behavior. 1343
1281 a study that found a deficit in retrieval behavior in postpartum First, although the literature on parental behavior covers a good 1344
1282 knockout female mice for DA transporter (DAT), but only in some range of species and strategies, our understanding of the neu- 1345
1283 genetic backgrounds (Morice et al., 2004; Spielewoy et al., 2000). ral basis of maternal behavior in these species is very uneven. 1346
1284 There is no information on changes in infanticidal or rapid pup- Increasing the diversity of species and the physiological condi- 1347
1285 induced parental responses in knockout mice for DAT or for other tions at which maternal behavior is studied will strengthen our 1348
1286 DA system genes (i.e. D1, D2, D4 receptors). However, in humans, understanding of how a certain brain substrate or circuitry has 1349
1287 polymorphisms for the dopaminergic system have been exten- been adapted to respond maternally under different conditions 1350
1288 sively investigated and variants that are less efficient in this system and with different modalities of mother–offspring interaction. For 1351
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1352 example, the comparisons of the neural basis of altricial vs. preco- follow the current trend that includes, in its analysis, aspects related 1418
1353 cial species, or of species requiring extensive vs. brief daily periods to the social and family context, as well as the style and dynamics 1419
1354 of mother–offspring interaction can provide information on dif- of parenting. These studies will necessarily require a multidisci- 1420
1355 ferent mechanisms that would be needed to maintain maternal plinary approach designed to assess which features of parenting are 1421
1356 motivation with or without the continuous stimulation by the off- uniquely human and which vary across cultures and species. The 1422
1357 spring. This comparative analysis or approach is informative given identifcation of the physiological and experiential causes of both 1423
1358 that existing adaptive mechanisms may remain mostly hidden or normative and maladaptive or inappropriate parenting in human 1424
1359 minimized in some species or contexts, but be activated or obvious populations is essential if we are to develop effective interventions 1425
1360 in others. and strategies to enhance sensitive and appropriate parenting skills 1426
1361 Second, focusing our studies on multiple species can also and practices. 1427
1362 provide information on the changes in neural substrate that support

1363 the different components of this complex behavior across lactation.
Uncited references Q15 1428
1364 Altricial and precocial offspring develop differently and require
1365 different kinds and degrees of attention from their mothers. Differ-
Sheehan and Numan (2002) and Bakermans-Kranenburg and 1429
1366 ent species use different sensory modalities for mother–offspring
van Ijzendoorn (2008). 1430
1367 interaction and the importance of different modalities changes
1368 across lactation and with the development of the young. We have
1369 advanced significantly in understanding the neural substrate that Acknowledgments 1431
1370 mediates some components of maternal behavior most commonly

1371 present in rodents (retrieval, licking, nursing). However, the role The authors want to thank the institutions and organizations 1432
1372 of mother’s vocalization, not investigated in rodents, is critical in that supported the Workshop Neural Basis of Maternal Motivation: 1433
1373 many species, including most ungulates and primates. The neural Relationship and Coordination with other social motivational sys- 1434
1374 basis of this aspect of maternal behavior and motivation has not tems and provided funds for the participation of investigators and 1435
1375 been explored in detail, and is one of the components of mater- students. We thank the School of Medicine (UdelaR) that hosted 1436
1376 nal behavior recruited during the search for displaced offspring in the meeting, and the Comisión Sectorial de Investigación Cientí- 1437
1377 many species. This is particularly interesting considering that this fica (CSIC, UdelaR), the French Embassy, the International Brain 1438
1378 highly motivated active seeking behavior eventually requires minor Research Organization (IBRO), and the Programme for the Devel- 1439
1379 or no displacement or movement of the mother. Furthermore, the opment of Basic Sciences (PEDECIBA, Uruguay) for their financial 1440
1380 switching of maternal activities and the offset of maternal behavior support. 1441
1381 should be regulated differently in species with precocial young than

1382 in those with altricial young, considering the quick development of References 1442
1383 motor and nutritional independence in precocial species. The neu-
1384 ral basis of these differences is likely the result of an adaptation Afonso, V.M., Sison, M., Lovic, V., Fleming, A.S., 2007. Medial prefrontal cortex lesions 1443
1385 to satisfy the needs of the offspring, including the strengthening of in the female rat affect sexual and maternal behavior and their sequential orga- 1444
nization. Behav. Neurosci. 121, 515–526. 1445
1386 sensory channels that are relevant to maintain maternal motivation
Algers, B., Uvnäs-Moberg, K., 2007. Maternal behavior in pigs. Horm. Behav. 52 (1), 1446
1387 at each specific developmental period. 78–85. 1447
1388 Third, the present discussion on the neural basis of maternal Bakermans-Kranenburg, M.J., van Ijzendoorn, M.H., 2008. Oxytocin receptor (OXTR) 1448
and serotonin transporter (5-HTT) genes associated with observed parenting. 1449
1389 behavior in different physiological and social contexts, and their
Soc. Cogn. Affect. Neurosci. 3 (2), 128–134. 1450
1390 regulation and adaptation across lactation, resulted in the formu- Bakermans-Kranenburg, M.J., van Ijzendoorn, M.H., Riem, M.M., Tops, M., Alink, L.R., 1451
1391 lation of several integrated neural models that could explain how 2012. Oxytocin decreases handgrip force in reaction to infant crying in females 1452
1392 the brain might adapt to these different situations. Here, we put without harsh parenting experiences. Soc. Cogn. Affect. Neurosci. (March). 1453
Barrett, J., Wonch, K.E., Gonzalez, A., Ali, N., Steiner, M., Hall, G.B., Fleming, A.S., 2012. 1454
1393 particular emphasis on the critical, but changing, function of the Maternal affect and quality of parenting experiences are related to amygdala 1455
1394 mPOA in the control of maternal behavior expressed under differ- response to infant faces. Soc. Neurosci., 2011. 1456
1395 ent physiological and social contexts. We incorporate into these Barrett, J., Fleming, A.S., 2011. Annual Research Review: all mothers are not cre- 1457
ated equal: neural and psychobiological perspectives on mothering and the 1458
1396 neural models the role of cortical regions in the organization of, importance of individual differences. J. Child Psychol. Psychiatry 52 (4), 368–397. 1459
1397 and switching between, different behaviors or motivations. We also Bauer, J.H., 1983. Effects of maternal state on the responsiveness to nest odors of 1460
1398 propose hypothetical changes in neural representation of different hooded rats. Physiol. Behav. 30, 229–232. 1461
Beach, F.A., Jaynes, J., 1956. Studies of maternal retrieving in rats. III. Sensory cues 1462
1399 subregions of the circuitry that supports maternal behavior, with involved in the lactating female’s response to her young. Behaviour 10, 104–125. 1463
1400 possible relevance in the proceess of short or long term mater- Bianco, I.H., Wilson, S.W., 2009. The habenular nuclei: a conserved asymmetric relay 1464
1401 nal adaptation and memory. We also discuss a neural model to station in the vertebrate brain. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 364 (1519), 1465
1005–1020. 1466
1402 explain the reduction or absence of inhibition of maternal behavior
Biben, M., Symmes, D., Bernhards, D., 1989. Contour variables in vocal communi- 1467
1403 in many species and how the brain might adapt to express maternal cation between squirrel monkey mothers and infants. Dev. Psychobiol. 22 (6), 1468
1404 behavior in those cases. 617–631. 1469
Bick, J., Dozier, M., 2010. Mothers’ and children’s concentrations of oxytocin follow- 1470
1405 Finally, we review the enormous contribution that animals
ing close, physical interactions with biological and non-biological children. Dev. 1471
1406 studies have made to our understanding of human maternal behav- Psychobiol. 52 (1), 100–107. 1472
1407 ior and motivation. We highlight the remarkable similarity in Blumberg, M.S., Alberts, J.R., 1991. On the significance of similarities between ultra- 1473
1408 many fundamental biological processes (including neural pro- sonic vocalizations of infant and adult rats. Neurosci. Biobehav. Rev. 15, 383–390. 1474
Bosch, O.J., Neumann, I.D., 2012. Both oxytocin and vasopressin are mediators of 1475
1409 cesses) found in animals and humans. However, we also highlight maternal care and aggression in rodents: from central release to sites of action. 1476
1410 that the neural basis of maternal motivation must be adapted to Horm. Behav. 61 (3), 293–303. 1477
1411 the particularities of the human condition and behavior. There- Bridges, R.S., 1996. Biochemical basis of parental behavior in the rat. In: Rosenblatt, 1478
J.S., Snowdon, C.T. (Eds.), Advance in the Study of Behavior, vol. 25. Parental 1479
1412 fore, we have put particular emphasis in this review on the role Care: Evolution, Mechanisms, and Adaptive Significance. Academic Press, pp. 1480
1413 of the cortex in the control of maternal behavior, in particular its 215–242. 1481
1414 role in executive functions related to maternal behavior. As part of Bridges, R.S., DiBiase, R., Loundes, D.D., Doherty, P.C., 1985. Prolactin stimulation of 1482
maternal behavior in female rats. Science 227 (4688), 782–784. 1483
1415 these investigations, we consider that new MRI studies provide an Bridges, R.S., Freemark, M.S., 1995. Human placental lactogen infusions into the 1484
1416 opportunity to reveal the neural basis of human parenting. We also medial preoptic area stimulate maternalbehavior in steroid-primed, nulliparous 1485
1417 suggest that studies on genetic aspects of maternal behavior should female rats. Horm. Behav. 29 (2), 216–226. 1486
ARTICLE IN PRESS
G Model
NBR 1756 1–18
1487 Bridges, R.S., Goldman, B.D., Bryant, L.P., 1974a. Serum prolactin concentrations and Febo, M., 2011. A bold view of the lactating brain: functional magnetic reso- 1573
1488 the initiation of maternal behavior in the rat. Horm. Behav. 5 (3), 219–226. nance imaging studies of suckling in awake dams. J. Neuroendocrinol. 23 (11), 1574
1489 Bridges, R.S., Mann, P.E., Coppeta, J.S., 1999. Hypothalamic involvement in the reg- 1009–1019. 1575
1490 ulation of maternal behavior in the rat: inhibitory roles for the ventromedial Feldman, R., Gordon, I., Zagoory-Sharon, O., 2011. Maternal and paternal 1576
1491 hypothalamus and the dorsal/anterior hypothalamic areas. J. Neuroendocrinol. plasma, salivary, and urinary oxytocin and parent-infant synchrony: consid- 1577
1492 11, 259–266. ering stress and affiliation components of human bonding. Dev. Sci. 14 (4), 1578
1493 Bridges, R.S., Zarrow, M.X., Goldman, B.D., Denenberg, V.H., 1974b. A developmental 752–761. 1579
1494 study of maternal responsiveness in the rat. Physiol. Behav. 12 (1), 149–151. Feldman, R., Weller, A., Zagoory-Sharon, O., Levine, A., 2007. Evidence for a neuroen- 1580
1495 Broad, K.D., Hinton, M.R., Keverne, E.B., Kendrick, K.M., 2002. Involvement of the docrinological foundation of human affiliation: plasma oxytocin levels across 1581
1496 medial prefrontal cortex in mediating behavioural responses to odour cues pregnancy and the postpartum period predict mother-infant bonding. Psychol. 1582
1497 rather than olfactory recognition memory. Neuroscience 114 (3), 715–729. Sci. 18 (11), 965–970. 1583
1498 Bruce, H.M., 1961. Observations on the suckling stimulus and lactation in the rat. J. Feldman, R., Zagoory-Sharon, O., Weisman, O., Schneiderman, I., Gordon, I., Maoz, 1584
1499 Reprod. Fert. 2, 17–34. R., Shalev, I., Ebstein, R.P., 2012. Sensitive parenting is associated with plasma 1585
1500 Buckley, K.M., 2001. Long-term breastfeeding: nourishment or nurturance? J. Hum. oxytocin and polymorphisms in the OXTR and CD38 genes. Biol. Psychiatry 72 1586
1501 Lact. 17 (4), 304–312. (3), 175–181. 1587
1502 Buttner, M.M., O‘Hara, M.W., Watson, D., 2012. The structure of women’s mood in Felton, T.M., Linton, L., Rosenblatt, J.S., Morrell, J.I., 1998. Intact neurons of the lateral 1588
1503 the early postpartum. Assessment 19 (2), 247–256. habenular nucleus are necessary for the nonhormonal, pup-mediated display of 1589
1504 Cameron, N.M., Shahrokh, D., Del Corpo, A., Dhir, S.K., Szyf, M., Champagne, F.A., maternal behaviour in sensitized virgin female rats. Behav. Neurosci. 112 (6), 1590
1505 Meaney, M.J., 2008. Epigenetic programming of phenotypic variations in repro- 1458–1465. 1591
1506 ductive strategies in the rat through maternal care. J. Neuroendocrinol. 20 (6), Ferreira, G., Meurisse, M., Gervais, R., Ravel, N., Lévy, F., 2001. Extensive immunole- 1592
1507 795–801. sions of basal forebrain cholinergic system impair offspring recognition in sheep. 1593
1508 Champagne, F., Diorio, J., Sharma, S., Meaney, M.J., 2001. Naturally occurring Neuroscience 106 (1), 103–116. 1594
1509 variations in maternal behavior in the rat are associated with differences in Fleischer, S., Slotnick, B.M., 1978. Disruption of maternal behavior in rats with 1595
1510 estrogen-inducible central oxytocin receptors. Proc. Natl. Acad. Sci. U. S. A. 98 lesions of the septal area. Physiol. Behav. 21 (2), 189–200. 1596
1511 (22), 12736–12741. Fleming, A.S., Luebke, C., 1981. Timidity prevents the virgin female rat from being 1597
1512 Chen, F.S., Kumsta, R., von Dawans, B., Monakhov, M., Ebstein, R.P., Heinrichs, M., a good mother: emotionality differences between nulliparous and parturient 1598
1513 2011. Common oxytocin receptor gene (OXTR) polymorphism and social sup- females. Physiol. Behav. 27 (5), 863–868. 1599
1514 port interact to reduce stress in humans. Proc. Natl. Acad. Sci. U. S. A. 108 (50), Fleming, A.S., Rosenblatt, J., 1974a. Olfactory regulation of maternal behavior in rats. 1600
1515 19937–19942. I. Effects of olfactory bulb removal in experienced and inexperienced lactating 1601
1516 Chirino, R., Beyer, C., González-Mariscal, G., 2007. Lesion to the main olfactory and cycling females. J. Comp. Physiol. Psychol. 86 (2), 221–232. 1602
1517 epithelium facilitates maternal behavior in virgin rabbits. Behav. Brain Res. 180, Fleming, A.S., Rosenblatt, J., 1974b. Olfactory regulation of maternal behavior 1603
1518 127–132. in rats. II. Effects of peripherally induced anosmia and lesions of the lat- 1604
1519 Corodimas, K.P., Rosenblatt, J.S., Canfield, M.E., Morrell, J.I., 1993. Neurons in the eral olfactory tract in pup-induced virgins. J. Comp. Physiol. Psychol. 86 (2), 1605
1520 lateral subdivision of the habenular complex mediate the hormonal onset of 233–246. 1606
1521 maternal behavior in rats. Behav. Neurosci. 107 (5), 827–843. Fleming, A.S., Rosenblatt, J., 1974c. Maternal behavior in the virgin and lactating rat. 1607
1522 Cosnier, J., 1963. Several problems posed by induced maternal behavior in rats. C. J. Comp. Physiol. Psychol. 86, 957–972. 1608
1523 R. Seances Soc. Biol. Fil. 157, 1611–1613. Fleming, A.S., Vaccarino, F., Luebke, C., 1980. Amygdaloid inhibition of maternal 1609
1524 Costa, B., Pini, S., Gabelloni, P., Abelli, M., Lari, L., Cardini, A., Muti, M., Gesi, C., Landi, behavior in the nulliparous female rat. Physiol. Behav. 25, 731–743. 1610
1525 S., Galderisi, S., Mucci, A., Lucacchini, A., Cassano, G.B., Martini, C., 2009. Oxytocin Fleming, A.S., Cheung, U., Myhal, N., Kessler, Z., 1989. Effects of maternal hormones 1611
1526 receptor polymorphisms and adult attachment style in patients with depression. on “timidity” and attraction to pup-related odors in female rats. Physiol. Behav. 1612
1527 Psychoneuroendocrinology 34 (10), 1506–1514. 46, 449–453. 1613
1528 Cramer, C.P., Thiels, E., Alberts, J.R., 1990. Weaning in rats: I. Maternal behavior. Dev. Fleming, A.S., Corter, C., Franks, P., Surbey, M., Schneider, B., Steiner, M., 1993. Post- 1614
1529 Psychobiol. 23 (6), 479–493. partum factors related to mother’s attraction to newborn infant odors. Dev. 1615
1530 Cromwell, H.C., 2011. Rat pup social motivation: a critical component of early Psychobiol. 26 (2), 115–132. 1616
1531 psychological development. Neurosci. Biobehav. Rev. 35 (5), 1284–1290. Fleming, A.S., Korsmit, M., 1996. Plasticity in the maternal circuit: effects of maternal 1617
1532 Cruz, M.L., Beyer, C., 1972. Effect of septal lesions on maternal behavior and lactation experience on Fos-Lir in hypothalamic, limbic, and cortical structures in the 1618
1533 in the rabbit. Physiol. Behav. 9, 361–365. postpartum rat. Behav. Neurosci. 110 (3), 567–582. 1619
1534 Da Costa, A.P.C., Broad, K.D., Kendrick, K.M., 1997. Olfactory memory and maternal Fleming, A.S., Ruble, D., Krieger, H., Wong, P.Y., 1997a. Hormonal and experiential 1620
1535 behaviour-induced changes in c-fos and zifr268 mRNA expression in the sheep correlates of maternal responsiveness during pregnancy and the puerperium in 1621
1536 brain. Mol. Brain Res. 46, 63–76. human mothers. Horm. Behav. 31 (2), 145–158. 1622
1537 Da Costa, A.P., Guevara-Guzman, R.G., Ohkura, S., Goode, J.A., Kendrick, K.M., 1996. Fleming, A.S., Steiner, M., Corter, C., 1997b. Cortisol, hedonics, and maternal respon- 1623
1538 The role of oxytocin release in the paraventricular nucleus in the control of siveness in human mothers. Horm. Behav. 32, 85–98. 1624
1539 maternal behaviour in the sheep. J. Neuroendocrinol. 8 (3), 163–177. French, J.A., Fite, J.E., Ross, C.N., 2008. Family life in marmosets: causes and con- 1625
1540 D’cunha, T.M., King, S.J., Fleming, A.S., Lévy, F., 2011. Oxytocin receptors in the sequences of variation in caregiving. In: Bridges, R.S. (Ed.), Neurobiology of the 1626
1541 nucleus accumbens shell are involved in the consolidation of maternal memory Parental Brain. Academic Press. 1627
1542 in postpartum rats. Horm. Behav. 59 (1), 14–21. Giardino, J., González, A., Steiner, M., Fleming, A.S., 2008. Effects of motherhood on 1628
1543 Deater-Deckard, K., Wang, Z., Chen, N., Bell, M.A., 2012. Maternal executive function, physiological and subjective responses to infant cries in teenage mothers: a com- 1629
1544 harsh parenting, and child conduct problems. J. Child Psychol. Psychiatry. parison with non-mothers and adult mothers. Horm. Behav. 53 (1), 149–158. 1630
1545 Denenberg, V.H., Taylor, R.E., Zarrow, M.X., 1969. Maternal behavior in the rat: an Gonzalez, A., Fleming, A.S., 2002. Artificial rearing causes changes in maternal 1631
1546 investigation and quantification of nest building. Behaviour 34 (1-2), 1–16. behavior and c-fos expression in juvenile female rats. Behav. Neurosci. 116 (6), 1632
1547 de Jong, T.R., Chauke, M., Harris, B.N., Saltzman, W., 2009. From here to pater- 999–1013. 1633
1548 nity: neural correlates of the onset of paternal behavior in California mice González-Mariscal, G., 2007. Mother rabbits and their offspring: timing is every- 1634
1549 (Peromyscus californicus). Horm. Behav. 56 (2), 220–231. thing. Dev. Psychobiol. 49, 71–76. 1635
1550 de Jong, T.R., Measor, K.R., Chauke, M., Harris, B.N., Saltzman, W., 2010. Brief González-Mariscal, G., Díaz-Sánchez, V., Melo, A.I., Beyer, C., Rosenblatt, J.S., 1994. 1636
1551 pup exposure induces Fos expression in the lateral habenula and serotoner- Maternal behavior in New Zealand white rabbits: quantification of somatic 1637
1552 gic caudal dorsal raphe nucleus of paternally experienced male California mice events, motor patterns and steroid plasma levels. Physiol. Behav. 55, 1081–1089. 1638
1553 (Peromyscus californicus). Neuroscience 169 (3), 1094–1104. González-Mariscal, G., Chirino, R., 2011. Exposure to pup odors before mating 1639
1554 Fahrbach, S.E., Morrell, J.I., Pfaff, D.W., 1984. Oxytocin induction of short-latency promotes attraction to such scents across pregnancy in rabbits. In: Society 1640
1555 maternal behavior in nulliparous, estrogen-primed female rats. Horm. Behav. for Behavioral Neuroendocrinology 15th Annual Meeting, Querétaro, México, 1641
1556 18 (3), 267–286. Abstract P2.23. 1642
1557 Fahrbach, S.E., Morrell, J.I., Pfaff, D.W., 1986. Possible role for endogenous oxytocin González-Mariscal, G., Chirino, R., Beyer, C., Rosenblatt, J.S., 2004a. Removal of the 1643
1558 in estrogen-facilitated maternal behavior in rats. Neuroendocrinology 40 (6), accessory olfactory bulbs facilitates maternal behavior in virgin rabbits. Behav. 1644
1559 526–532. Brain Res. 152, 89–95. 1645
1560 Farrell, W.J., Alberts, J.R., 2002. Maternal responsiveness to infant Norway rat (Rat- González-Mariscal, G., Chirino, R., Flores-Alonso, J.C., Rosenblatt, J.S., Beyer, C., 1646
1561 tus norvegicus) ultrasonic vocalizations during the maternal behavior cycle and 2004b. Intracerebroventricular injections of prolactin counteract the antago- 1647
1562 after steroid and experiential induction regimens. J. Comp. Psychol. 116 (3), nistic effect of bromocriptine on rabbit maternal behaviour. J. Neuroendocrinol. 1648
1563 286–296. 16 (12), 949–955. 1649
1564 Featherstone, R.E., Fleming, A.S., Ivy, G.O., 2000. Plasticity in the maternal circuit: González-Mariscal, G., Chirino, R., Rosenblatt, J.S., Beyer, C., 2005. Forebrain implants 1650
1565 effects of experience and partum condition on brain astrocyte number in female of estradiol stimulate maternal nest-building in ovariectomized rabbits. Horm. 1651
1566 rats. Behav. Neurosci. 114 (1), 158–172. Behav. 47 (3), 272–279. 1652
1567 Febo, M., Stolberg, T.L., Numan, M., Bridges, R.S., Kulkarni, P., Ferris, C.F., 2008. Nurs- González-Mariscal, G., Jiménez, A., Chirino, R., Beyer, C., 2009. Motherhood and 1653
1568 ing stimulation is more than tactile sensation: it is a multisensory experience. nursing stimulate c-FOS expression in the rabbit forebrain. Behav. Neurosci. 123 1654
1569 Horm. Behav. 54 (2), 330–339. (4), 731–739. 1655
1570 Febo, M., Felix-Ortiz, A.C., Johnson, T.R., 2010. Inactivation or inhibition of neu- González-Mariscal, G., Lemus, A.C., Aguilar-Roblero, R., 2011. Rabbit nursing shows 1656
1571 ronal activity in the medial prefrontal cortex largely reduces pup retrieval and circadian periodicity and is modulated by suckling stimulation characteristics. 1657
1572 grouping in maternal rats. Brain Res. 1325, 77–88. In: III World Congress of Chronobiology, Puebla, México, Abstract P108. 1658
ARTICLE IN PRESS
G Model
NBR 1756 1–18
1659 González-Mariscal, G., Melo, A.I., Jiménez, P., Beyer, C., Rosenblatt, J.S., 1996. Estra- Kinsley, C.H., Bardi, M., Karelina, K., Rima, B., Christon, L., Friedenberg, J., Griffin, 1745
1660 diol, progesterone, and prolactin facilitate maternal nest-building in rabbits. J. G., 2008. Motherhood induces and maintains behavioral and neural plasticity 1746
1661 Neuroendocrinol. 8, 901–907. across the lifespan in the rat. Arch. Sex. Behav. 37 (1), 43–56. 1747
1662 González-Mariscal, G., Poindron, P., 2002. Parental care in mammals: immediate Kinsley, C.H., Lambert, K.G., 2008. Reproduction-induced neuroplasticity: natural 1748
1663 internal and sensory factors of control. In: Pfaff, D., Arnold, A., Etgen, A., Fahrbach, behavioural and neuronal alterations associated with the production and care 1749
1664 S., Rubin, R. (Eds.), Hormones, Brain and Behavior. Academic Press, San Diego, of offspring. J. Neuroendocrinol. 20, 515–525. 1750
1665 pp. 215–298. Kirkpatrick, B., Kim, J.W., Insel, T.R., 1994. Limbic system fos expression associated 1751
1666 González-Mariscal, G., Rosenblatt, J.S., 1996. Maternal behavior in rabbits: a histor- with paternal behavior. Brain Res. 658 (1–2), 112–118. 1752
1667 ical and multidisciplinary perspective. In: Rosenblatt, J.S., Snowdon, C.T. (Eds.), Kovacs, G., Sarnyai, L., Babarczy, Z., Szabo, B., Telegdy, G.G., 1990. The role of 1753
1668 Parental Care: Evolution, Mechanisms and Adaptive Significance, vol. 25. Aca- oxytocin-dopamine interactions in cocaine-induced locomotor hyperactivity. 1754
1669 demic Press, San Diego, pp. 333–360. Neuropharmacology 29 (4), 365–368. 1755
1670 González-Mariscal, G., Toribio, A., Gallegos-Huicochea, J.A., Serrano-Meneses, M.A., Kuroda, K.O., Tachikawa, K., Yoshida, S., Tsuneoka, Y., Numan, M., 2011. Neuromolec- 1756
1671 2012. The characteristics of suckling stimulation determine the daily dura- ular basis of parental behavior in laboratory mice and rats: with special emphasis 1757
1672 tion of mother-young contact and milk output in rabbits. Dev. Psychobiol., on technical issues of using mouse genetics. Prog. Neuropsychopharmacol. Biol. 1758
1673 http://dx.doi.org/10.1002/dev.21071. Psychiatry 35 (5), 1205–1231. 1759
1674 Grimsley, J.M., Monaghan, J.J., Wenstrup, J.J., 2011. Development of social vocaliza- Landgraf, R., Neumann, I.D., 2004. Vasopressin and oxytocin release within the brain: 1760
1675 tions in mice. PloS One 6 (3), 7460. a dynamic concept of multiple and variable modes of neuropeptide communi- 1761
1676 Grosvenor, C., Mena, F., 1974. Neural and hormonal control of milk secretion and cation. Front. Neuroendocrinol. 25 (3-4), 150–176. 1762
1677 milk ejection. In: Larson, B.L., Smith, V.R. (Eds.), Lactation: A Comprehensive Lee, A.W., Brown, R.E., 2002. Medial preoptic lesions disrupt parental behavior in 1763
1678 Treatise. Academic Press, New York, pp. 227–276. both male and female California Mice (Peromyscus californicus). Behav. Neu- 1764
1679 Hansen, S., Ferreira, A., 1986. Food intake, aggression, and fear behavior in the rosci. 116 (6), 968–975. 1765
1680 mother rat: control by neural systems concerned with milk ejection and mater- Lee, A.W., Brown, R.E., 2007. Comparison of medial preoptic, amygdala, and nucleus 1766
1681 nal behavior. Behav. Neurosci. 100 (1), 64–70. accumbens lesions on parental behavior in California mice (Peromyscus califor- 1767
1682 Harmon, K.M., Cromwell, H.C., Burgdorf, J., Moskal, J.R., Brudzynski, S.M., Kroes, R.A., nicus). Physiol. Behav. 92 (4), 617–628. 1768
1683 Panksepp, J., 2008. Rats selectively bred for low levels of 50 kHz ultrasonic Lee, S.S., Chronis-Tuscano, A., Keenan, K., Pelham, W.E., Loney, J., Van Hulle, 1769
1684 vocalizations exhibit alterations in early social motivation. Dev. Psychobiol. 50, C.A., Cook, E.H., Lahey, B.B., 2010. Association of maternal dopamine 1770
1685 322–331. transporter genotype with negative parenting: evidence for gene x envi- 1771
1686 Hikosaka, O., Sesack, S.R., Lecourtier, L., Shepard, P.D., 2008. Habenula: cross- ronment interaction with child disruptive behavior. Mol. Psychiatry. 15 (5), 1772
1687 road between the basal ganglia and the limbic system. J. Neurosci. 28 (46), 548–558. 1773
1688 11825–11829. Lee, A., Clancy, S., Fleming, A.S., 1999. Mother rats bar-press for pups: effects of 1774
1689 Hiryu, S., Riquimaroux, H., 2011. Developmental changes in ultrasonic vocalizations lesions of the mpoa and limbic sites on maternal behavior and operant respon- 1775
1690 by infant Japanese echolocating bats, Pipistrellus abramus. J. Acoust. Soc. Am. ding for pup-reinforcement. Behav. Brain Res. 10, 15–31. 1776
1691 130 (4), 147–153. Letourneau, N.L., Dennis, C.L., Benzies, K., Duffett-Leger, L., Stewart, M., 1777
1692 Hrdy, S.B., 2008. Cooperative breeding and the paradox of facultative fathering. Tryphonopoulos, P.D., Este, D., Watson, W., 2012. Postpartum depression is a 1778
1693 Chapter 26. In: Bridges, R.S. (Ed.), Neurobiology of the Parental Brain. Academic family affair: addressing the impact on mothers, fathers, and children. Issues 1779
1694 Press, pp. 407–416. Ment. Health Nurs. 33 (7), 445–457. 1780
1695 Insel, T.R., Harbaugh, C.R., 1989. Lesions of the hypothalamic paraventricular nucleus Lévy, F., Poindron, P., Le Neindre, P., 1983. Attraction and repulsion by amniotic 1781
1696 disrupt the initiation of maternal behavior. Physiol. Behav. 45 (5), 1033–1041. fluids and their olfactory control in the ewe around parturition. Physiol. Behav. 1782
1697 Izar, P., Verderane, M.P., Visalberghi, E., Ottoni, E.B., Gomes De Oliveira, M., Shirley, 31 (5), 687–692. 1783
1698 J., Fragaszy, D., 2006. Cross-genus adoption of a marmoset (Callithrix jacchus) Lévy, F., Kendrick, K.M., Keverne, E.B., Piketty, V., Poindron, P., 1992. Intracerebral 1784
1699 by wild capuchinmonkeys (Cebus libidinosus): case report. Am. J. Primatol. 68 oxytocin is important for the onset of maternal behavior in inexperi- 1785
1700 (7), 692–700. enced ewes delivered under peridural anesthesia. Behav. Neurosci. 106 (2), 1786
1701 Kaitz, M., Shalev, I., Sapir, N., Devor, N., Samet, Y., Mankuta, D., Ebstein, R.P., 2010. 427–432. 1787
1702 Mothers’ dopamine receptor polymorphism modulates the relation between Lévy, F., Kendrick, K.M., Goode, J.A., Guevara-Guzman, R., Keverne, E.B., 1995. Oxy- 1788
1703 infant fussiness and sensitive parenting. Dev. Psychobiol. 52 (2), 149–157. tocin and vasopressin release in the olfactory bulb of parturient ewes: changes 1789
1704 Kalamatianos, T., Faulkes, C.G., Oosthuizen, M.K., Poorun, R., Bennett, N.C., Coen, with maternal experience and effects on acetylcholine, gamma-aminobutyric 1790
1705 C.W., 2010. Telencephalic binding sites for oxytocin and social organization: a acid, glutamate and noradrenaline release. Brain Res. 669 (2), 197–206. 1791
1706 comparative study of eusocial naked mole-rats and solitary cape mole-rats. J. Lévy, F., Keller, M., 2008. Neurobiology of maternal behavior in sheep. Adv. Stud. 1792
1707 Comp. Neurol. 518 (10), 1792–1813. Behav. 38, 399–437. 1793
1708 Kalinichev, M., Rosenblatt, J.S., Morrell, J.I., 2000a. The medial preoptic area, nec- Lévy, F., Keller, M., 2009. Olfactory mediation of maternal behavior in selected 1794
1709 essary for adult maternal behavior in rats, is only partially established as a mammalian species. Behav. Brain Res. 200 (2), 336–345. 1795
1710 component of the neural circuit that supports maternal behavior in juvenile L’Heureux, N., Lucherini, M., Festa-Bianchet, M., Jorgenson, J.T., 1995. Density- 1796
1711 rats. Behav. Neurosci. 114 (1), 196–210. dependent mother–yearling association in bighorn sheep. Anim. Behav. 49, 1797
1712 Kalinichev, M., Rosenblatt, J.S., Nakabeppu, Y., Morrell, J.I., 2000b. Induction of c- 901–910. 1798
1713 fos-like and fosB-like immunoreactivity reveals forebrain neuronal populations Lonstein, J.S., Stern, J.M., 1998. Site and behavioral specificity of periaqueductal gray 1799
1714 involved differentially in pup-mediated maternal behavior in juvenile and adult lesions on postpartum sexual, maternal, and aggressive behaviors in rats. Brain 1800
1715 rats. J. Comp. Neurol. 416 (1), 45–78. Res. 804 (1), 21–35. 1801
1716 Kapeller, P.M., 1998. Nests, tree holes, and the evolution of primate life histories. Love, G., Torrey, N., McNamara, I., Morgan, M., Banks, M., Hester, N.W., Glasper, 1802
1717 Am. J. Primatol. 46, 7–33. E.R., Devries, A.C., Kinsley, C.H., Lambert, K.G., 2005. Maternal experience 1803
1718 Katz, L.F., Ball, G.F., Nelson, R.J., 1999. Elevated Fos-like immunoreactivity in the produces long-lasting behavioral modifications in the rat. Behav. Neurosci. 119 1804
1719 brains of postpartum female prairie voles, Microtus ochrogaster. Cell Tissue Res. (4), 1084–1096. 1805
1720 298 (3), 425–435. Lovic, V., Fleming, A.S., 2004. Artificially-reared female rats show reduced prepulse 1806
1721 Keebaugh, A.C., Young, L.J., 2011. Increasing oxytocin receptor expression in the inhibition and deficits in the attentional set shifting task-reversal of effects with 1807
1722 nucleus accumbens of pre pubertal female prairie voles enhances alloparental maternal-like licking stimulation. Behav. Brain Res. 148, 209–219. 1808
1723 responsiveness and partner preference formation as adults. Horm. Behav. 60 (5), Lucas, B.K., Ormandy, C.J., Binart, N., Bridges, R.S., Kelly, P.A., 1998. Null mutation of 1809
1724 498–504. the prolactin receptor gene produces a defect in maternal behavior. Endocrinol- 1810
1725 Keller, M., Meurisse, M., Lévy, F., 2004a. Mapping the neural substrates involved in ogy 139 (10), 4102–4107. 1811
1726 maternal responsiveness and lamb olfactory memory in parturient ewes using Macbeth, A.H., Stepp, J.E., Lee, H.J., Young 3rd, W.S., Caldwell, H.K., 2010. Normal 1812
1727 Fos imaging. Behav. Neurosci. 118 (6), 1274–1284. maternal behavior, but increased pup mortality, in conditional oxytocinreceptor 1813
1728 Keller, M., Perrin, G., Meurisse, M., Ferreira, G., Lévy, F., 2004b. Cortical and medial knockout females. Behav. Neurosci. 124 (5), 677–685. 1814
1729 amygdala are both involved in the formation of olfactory offspring memory in Macdonald, D.W., Herrera, E.A., Taber, A.B., Moreira, J.R., 2007. Social organization 1815
1730 sheep. Eur. J. Neurosci. 20 (12), 3433–3441. and resource use in capybaras and maras. Chapter 33. In: Wolff, J.O., Sherman, 1816
1731 Keller, M., Meurisse, M., Lévy, F., 2005. Mapping of brain networks involved in P.W. (Eds.), Rodent Societies: An Ecological and Evolutionary Perspective. 1817
1732 consolidation of lamb recognition memory. Neuroscience 133, 359–369. Martínez-Gómez, M., Juárez, M., Distel, H., Hudson, R., 2004. Overlapping litters and 1818
1733 Kendrick, K.M., 2000. Oxytocin, motherhood and bonding. Exp. Physiol. 85, 111–124. reproductive performance in the domestic rabbit. Physiol. Behav. 82, 629–636. 1819
1734 Kendrick, K.M., Keverne, E.B., Baldwin, B.A., 1987. Intracerebroventricular oxytocin Mattson, B.J., Williams, S., Rosenblatt, J.S., Morrell, J.I., 2001. Comparison of two pos- 1820
1735 stimulates maternal behaviour in the sheep. Neuroendocrinology 46 (1), 56–61. itive reinforcing stimuli: pups and cocaine throughout the postpartum period. 1821
1736 Kerth, G., 2008. Causes and consequences of sociality in bats. Bioscience 58 (8), Behav. Neurosci. 115 (3), 683–694. 1822
1737 737–746. Mayer, A.D., 1983. The ontogeny of maternal behaviour in rodents. In: Elwood, R.W. 1823
1738 Kim, P., Feldman, R., Mayes, L.C., Eicher, V., Thompson, N., Leckman, J.F., Swain, J.E., (Ed.), Parental Behaviour in Rodents. Wiley & Sons Ltd., pp. 1–19. 1824
1739 2011. Breastfeeding, brain activation to own infant cry, and maternal sensitivity. Mayer, A.D., Rosenblatt, J.S., 1979. Ontogeny of maternal behavior in the laboratory 1825
1740 J. Child Psychol. Psychiatry 52 (8), 907–915. rat: early origins in 18- to 27-day-old young. Dev. Psychobiol. 12 (5), 407–424. 1826
1741 Kimble, D.P., 1997. Didelphid behavior. Neurosci. Biobehav. Rev. 21 (3), 361–369. Mileva-Seitz, V., Fleming, A.S., Meaney, M.J., Mastroianni, A., Sinnwell, J.P., Steiner, 1827
1742 Kinsley, C.H., Bridges, R.S., 1990. Morphine treatment and reproductive condition M., Atkinson, L., Levitan, R.D., Matthews, S.G., Kennedy, J.L., Sokolowski, M.B., 1828
1743 alter olfactory preferences for pup and adult male odors in female rats. Dev. 2012. Dopamine receptors D1 and D2 are related to observed maternal behavior. 1829
1744 Psychobiol. 23 (4), 331–347. Genes Brain Behav. 11 (6), 684–694. 1830
ARTICLE IN PRESS
G Model
NBR 1756 1–18
1831 Morice, E., Denis, C., Giros, B., Nosten-Bertrand, M., 2004. Phenotypic expression of Pedersen, C.A., Vadlamudi, S.V., Boccia, M.L., Amico, J.A., 2006. Maternal behav- 1917
1832 the targeted null-mutation in the dopamine transporter gene varies as a function ior deficits in nulliparous oxytocin knockout mice. Genes Brain Behav. 5 (3), 1918
1833 of the genetic background. Eur. J. Neurosci. 20 (1), 120–126. 274–281. 1919
1834 Motomura, N., Shimizu, K., Shimizu, M., Aoki-Komori, S., Taniguchi, K., Serizawa, I., Pereira, M., 2006. Nonselective maternal bonding but pup recognition in the sub- 1920
1835 Saito, T.R., 2002. A comparative study of isolation-induced ultrasonic vocaliza- terranean rodent Ctenomys pearsoni. J. Comp. Psychol. 120 (4), 411–415. 1921
1836 tion in rodent pups. Exp. Anim. 51 (2), 187–190. Pereira, M., Morrell, J.I., 2009. The changing role of the medial preoptic area in 1922
1837 Nakamichi, M., Yanada, K., 2009. Distribution of dorsal carriage among simians. the regulation of maternal behavior across the postpartum period: facilitation 1923
1838 Primates 50 (2), 153–168. followed by inhibition. Behav. Brain Res. 205 (1), 238–248. 1924
1839 Nephew, B.C., Caffrey, M.K., Felix-Ortiz, A.C., Ferris, C.F., Febo, M., 2009. Blood Pereira, M., Morrell, J.I., 2011. Functional mapping of the neural circuitry of rat 1925
1840 oxygen level-dependent signal responses in corticolimbic ‘emotions’ circuitry maternal motivation: effects of site-specific transient neural inactivation. J. Neu- 1926
1841 of lactating rats facing intruder threat to pups. Eur. J. Neurosci. 30 (5), roendocrinol. 23 (11), 1020–1035. 1927
1842 934–945. Perrin, G., Meurisse, M., Lévy, F., 2007. Inactivation of the medial preoptic area or 1928
1843 Neumann, I.D., Johnstone, H.A., Hatzinger, M., Liebsch, G., Shipston, M., Russell, the bed nucleus of the stria terminalis differentially disrupts maternal behavior 1929
1844 J.A., Landgraf, R., Douglas, A.J., 1998. Attenuated neuroendocrine responses to in sheep. Horm. Behav. 52, 461–473. 1930
1845 emotional and physical stressors in pregnant rats involve adenohypophysial Peterson, G., Mason, G.A., Barakat, A.S., Pedersen, C.A., 1991. Oxytocin selectively 1931
1846 changes. J. Physiol. 508, 289–300. increases holding and licking of neonates in preweanling but not postweanling 1932
1847 Nishimori, K., Young, L.J., Guo, Q., Wang, Z., Insel, T.R., Matzuk, M.M., 1996. Oxy- juvenile rats. Behav. Neurosci. 105 (3), 470–477. 1933
1848 tocin is required for nursing but is not essential for parturition or reproductive Poindron, P., Le Neindre, P., 1980. Endocrine and sensory regulation of maternal 1934
1849 behavior. Proc. Natl. Acad. Sci. U.S.A. 93 (21), 11699–11704. behavior in the ewe. Adv. Study Behav. 11, 75–119. 1935
1850 Nissen, E., Gustavsson, P., Widström, A.M., Uvnäs-Moberg, K., 1998. Oxytocin, pro- Poindron, P., Lévy, F., Krehbiel, D., 1988. Genital, olfactory, and endocrine inter- 1936
1851 lactin, milk production and their relationship with personality traits in women actions in the development of maternal behavior in the parturient ewe. 1937
1852 after vaginal delivery or Cesarean section. J. Psychosom. Obstet. Gynaecol. 19 Psychoneuroendocrinology 13, 99–125. 1938
1853 (1), 49–58. Poindron, P., Lévy, F., Keller, M., 2007. Maternal responsiveness and maternal selec- 1939
1854 Noirot, E., 1972. The onset of maternal behavior in rats, hamsters, and mice: a tivity in domestic sheep and goats: the two facets of maternal attachment. Dev. 1940
1855 selective review. Adv. Study Behav. 4, 107–141. Psychobiol. 49 (1), 54–70. 1941
1856 Nowak, R., Keller, S.M., Lévy, F., 2011. Mother–young relationships in sheep: a Porter, R.H., Cernoch, J.M., McLaughlin, F.J., 1983. Maternal recognition of neonates 1942
1857 model for a multidisciplinary approach of the study of attachment in mammals. through olfactory cues. Physiol. Behav. 30, 151–154. 1943
1858 J. Neuroendocrinol. 23, 1042–1053. Qi, J., Yang, J.-Y., Song, M., Li, Y., Wang, F., Wu, Ch-F., 2008. Inhibition by oxytocin 1944
1859 Numan, M., 2006. Hypothalamic neural circuits regulating maternal responsiveness of methamphetamine-induced hyperactivity related to dopamine turnover in 1945
1860 toward infants. Behav. Cogn. Neurosci. Rev. 5, 163–190. the mesolimbic region in mice. Naunyn-Schmiedeberg’s Arch. Pharmacol. 376, 1946
1861 Numan, M., 2007. Motivational systems and the neural circuitry of maternal behav- 441–448. 1947
1862 ior in the rat. Dev. Psychobiol. 49 (1), 12–21. Qi, J., Yang, J.-Y., Wang, F., Zhao, Y.-N., Song, M., Wu, Ch-F., 2009. Effects of oxytocin 1948
1863 Numan, M., Bress, J.A., Ranker, L.R., Gary, A.J., Denicola, A.L., Bettis, J.K., Knapp, on methamphetamine-induced conditioned place preference and the possible 1949
1864 S.E., 2010. The importance of the basolateral/basomedial amygdala for goal- role of glutamatergic neurotransmission in the medial prefrontal cortex of mice 1950
1865 directed maternal responses in postpartum rats. Behav. Brain Res. 214 (2), in reinstatement. Neuropharmacology 56, 856–865. 1951
1866 368–376. Ragnauth, A.K., Devidze, N., Moy, V., Finley, K., Goodwillie, A., Kow, L.M., Muglia, 1952
1867 Numan, M., Corodimas, K.P., Numan, M.J., Factor, E.M., Piers, W.D., 1988. L.J., Pfaff, D.W., 2005. Female oxytocin gene knockout mice, in a semi-natural 1953
1868 Axon.sparing lesions of the preoptic region and substantia innominata disrupt environment, display exaggerated aggressive behavior. Genes Brain Behav. 4 (4), 1954
1869 maternal behavior in rats. Behav. Neurosci. 102 (3), 381–396. 229–239. 1955
1870 Numan, M., Insel, T.R., 2003. The Neurobiology of Parental Behavior. Springer-Verlag, Ralls, K., Lundrigan, B., Kranz, K., 1986. Mother-Young relationship in captive ungu- 1956
1871 New York, Inc. lates: variability and clustering. Anim. Behav. 34, 134–145. 1957
1872 Numan, M., Numan, M.J., Schwarz, J.M., Neuner, C.M., Flood, T.F., Smith, C.D., 2005b. Rees, S.L., Panesar, S., Steiner, M., Fleming, A.S., 2004. The effects of adrenalectomy 1958
1873 Medial preoptic area interactions with the nucleus accumbens-ventral pallidum and corticosterone replacement on maternal behavior in the postpartum rat. 1959
1874 circuit and maternal behavior in rats. Behav. Brain Res. 158 (1), 53–68. Horm. Behav. 46 (4), 411–419. 1960
1875 Numan, M., Fleming, A.S., Lévy, F., 2006. Maternal behavior. In: Neill, J.D. (Ed.), Knobil Reisbick, S., Rosenblatt, J.S., Mayer, A.D., 1975. Decline of maternal behavior in the 1961
1876 and Neill’s Physiology of Reproduction. Elsevier, San Diego, pp. 1921–1993. virgin and lactating rat. J. Comp. Physiol. Psychol. 89, 722–732. 1962
1877 Numan, M., Stolzenberg, D.S., 2009. Medial preoptic area interactions with Roberts, R.L., Miller, A.K., Taymans, S.E., Carter, C.S., 1998. Role of social and 1963
1878 dopamine neural systems in the control of the onset and maintenance of mater- endocrine factors in alloparental behavior of prairie voles (Microtus ochro- 1964
1879 nal behavior in rats. Front. Neuroendocrinol. 30, 46–64. gaster). Can. J. Zool. 76, 1862–1868. 1965
1880 Ogawa, S., Eng, V., Taylor, J., Lubahn, D.B., Korach, K.S., Pfaff, D.W., 1998. Roles of Rosenblatt, J.S., 1967. Non-hormonal basis of maternal behavior in the rat. Science 1966
1881 estrogen receptor-alpha gene expression in reproduction-related behaviors in 156, 1512–1514. 1967
1882 female mice. Endocrinology 139 (12), 5070–5081. Rosenblatt, J.S., Siegel, H., 1981. Factors governing the onset and maintenance of 1968
1883 Olazábal, D.E., Kalinichev, M., Morrell, J.I., Rosenblatt, J.S., 2002. MPOA cytotoxic maternal behavior among non-primate mammals. In: Gubernick, D.J., Klopfer, 1969
1884 lesions and maternal behavior in the rat: effects of midpubertal lesions on mater- P.H. (Eds.), Parental Care in Mammals. Plenum Press, New York, pp. 13–76. 1970
1885 nal behavior and the role of ovarian hormones in maturation of MPOA control Rowland, D.L., 1981. Effects of pregnancy on the maintenance of maternal behavior 1971
1886 of maternal behavior. Horm. Behav. 41 (2), 126–138. in the rat. Behav. Neural Biol. 31, 225–235. 1972
1887 Olazábal, D.E., Morrell, J.I., 2005. Juvenile rats show reduced c-fos activity in neu- Salmaso, N., Nadeau, J., Woodside, B., 2009. Steroid hormones and maternal expe- 1973
1888 ral sites associated with aversion to pups and inhibition of maternal behavior. rience interact to induce glial plasticity in the cingulate cortex. Eur. J. Neurosci. 1974
1889 Behav. Neurosci. 119 (4), 1097–1110. 29, 786–794. 1975
1890 Olazábal, D.E., Pereira, M., Agrati, D., Ferreira, A., Fleming, A.S., González-Mariscal, Sarnyai, Z., Babarczy, B., Krivan, M., Szabo, G., Kovacs, G., Barth, L., Telegdy, T.G., 1991. 1976
1891 G., Lévy, F., Lucion, A.B., Morrell, J.I., Numan, M., Uriarte, N. New theoretical Selective attenuation of cocaine-induced stereotyped behaviour by oxytocin: 1977
1892 and experimental approaches on maternal motivation in mammals. Neurosci. putative role of basal forebrain target sites. Neuropeptides 19, 511–556. 1978
Q16
1893 Biobehav. Rev., submitted for publication-a. Schneider, J.S., Stone, M.K., Wynne-Edwards, K.E., Horton, T.H., Lydon, J., O‘Malley, 1979
1894 Olazábal, D.E., Villagrán, M., González-Pensado, S.X., Ungerfeld, R. Maternal behavior B., Levine, J.E., 2003. Progesterone receptors mediate male aggression toward 1980
1895 and early development of pampas deer (Ozotoceros bezoarticus) fawns in a semi- infants. Proc. Natl. Acad. Sci. U.S.A. 100 (5), 2951–2956. 1981
Q17
1896 captive environment. J. Ethol., submitted for publication-b. Schorscher-Petcu, A., Dupré, A., Tribollet, E., 2009. Distribution of vasopressin and 1982
1897 Olazábal, D.E., Young, L.J., 2005. Variability in spontaneous maternal behavior is oxytocin binding sites in the brain and upper spinal cord of the common mar- 1983
1898 associated with anxiety-like behavior and affiliation in naïve juveniles and adult moset. Neurosci. Lett. 461 (3), 217–222. 1984
1899 female prairie voles (Microtus ochrogaster). Dev. Psychobiol. 47, 166–178. Sèbe, F., Aubin, T., Boué, A., Poindron, P., 2008. Mother-young vocal communication 1985
1900 Olazábal, D.E., Young, L.J., 2006a. Species and individual differences in juvenile and acoustic recognition promote preferential nursing in sheep. J. Exp. Biol. 211, 1986
1901 female alloparental care are associated with oxytocin receptor density in the 3554–3562. 1987
1902 striatum and the lateral septum. Horm. Behav. 49 (5), 681–687. Shahrokh, D.K., Zhang, T., Diorio, J., Gratton, A., Meaney, M.J., 2010. Oxytocin- 1988
1903 Olazábal, D.E., Young, L.J., 2006b. Oxytocin receptors in the nucleus accumbens dopamine interactions mediate variations in maternal behavior in the rat. 1989
1904 facilitate “spontaneous” maternal behavior in adult female prairie voles. Neu- Endocrinology 151, 2276–2286. 1990
1905 roscience 141 (2), 559–568. Shams, S., Pawluski, J.L., Chatterjee-Chakraborty, M., Oatley, H., Mastroianni, A., 1991
1906 Oxley, G., Fleming, A.S., 2000. The effects of medial preoptic area and amygdala Fleming, A.S., 2012. Dendritic morphology in the striatum and hypothalamus 1992
1907 lesions on maternal behavior in the juvenile rat. Dev. Psychobiol. 37, 253–265. differentially exhibits experience-dependent changes in response to maternal 1993
1908 Pedersen, C.A., Caldwell, J.D., Johnson, M.F., Fort, S.A., Prange Jr., A.J., 1985. Oxy- care and early social isolation. Behav. Brain Res. 233, 79–89. 1994
1909 tocin antiserum delays onset of ovarian steroid-induced maternal behavior. Sheehan, T.P., Cirrito, J., Numan, M.J., Numan, M., 2000. Using c-fos immunocyto- 1995
1910 Neuropeptides 6 (2), 175–182. chemistry to identify forebrain regions that may inhibit maternal behavior in 1996
1911 Pedersen, C.A., Prange Jr., A.J., 1979. Induction of maternal behavior in virgin rats rats. Behav. Neurosci. 114 (2), 337–352. 1997
1912 after intracerebroventricular administration of oxytocin. Proc. Natl. Acad. Sci. U. Sheehan, T., Numan, M., 2002. Estrogen, progesterone, and pregnancy termina- 1998
1913 S. A. 76 (12), 6661–6665. tion alter neural activity in brain regions that control maternal behavior in rats. 1999
1914 Pedersen, C.A., Caldwell, J.D., Walker, C., Ayers, G., Mason, G.A., 1994. Oxytocin acti- Neuroendocrinology 75 (1), 12–23. 2000
1915 vates the postpartum onset of rat maternal behavior in the ventral tegmental Sheng, M., Greenberg, M.E., 1990. The regulation and function of c-fos and other 2001
1916 and medial preoptic areas. Behav. Neurosci. 108 (6), 1163–1171. immediate early genes in the nervous system. Neuron 4 (4), 477–485. 2002
ARTICLE IN PRESS
G Model
NBR 1756 1–18
2003 Skrundz, M., Bolten, M., Nast, I., Hellhammer, D.H., Meinlschmidt, G., 2011. Plasma Torriani, M.V.G., Vannoni, E., McElligott, A.G., 2006. Mother-young recognition 2035
2004 oxytocin concentration during pregnancy is associated with development of in an ungulate hider species: a unidirectional process. Am. Nat. 168 (3), 2036
2005 postpartum depression. Neuropsychopharmacology 36 (9), 1886–1893. 412–420. 2037
2006 Siegel, H.I., Rosenblatt, J.S., 1975. Hormonal basis of hysterectomy-induced maternal Tu, M.T., Lupien, S.J., Walker, C.D., 2005. Measuring stress responses in postpartum 2038
2007 behavior during pregnancy in the rat. Horm. Behav. 6 (3), 211–222. mothers: perspectives from studies in human and animal populations. Stress 8 2039
2008 Slotnick, B.M., 1967. Disturbances of maternal behavior in the rat following lesions (1), 19–34. 2040
2009 of the cingulatecortex. Behaviour 29 (2), 204–236. Uriarte, N., Ferreira, A., Rosa, X.F., Sebben, V., Lucion, A.B., 2008. Overlapping litters 2041
2010 Slotnick, B.M., Nigrosh, B.J., 1975. Maternal behavior of mice with cingulate cortical, in rats: effects on maternal behavior and offspring emotionality. Physiol. Behav. 2042
2011 amygdala, or septal lesions. J. Comp. Physiol. Psychol. 88 (1), 118–127. 93 (4-5), 1061–1070. 2043
2012 Spielewoy, C., Roubert, C., Hamon, M., Nosten-Bertrand, M., Betancur, C., Giros, Uriarte, N., Ferreira, A., Rosa, X.F., Lucion, A.B., 2009. Effects of litter-overlapping on 2044
2013 B., 2000. Behavioural disturbances associated with hyperdopaminergia in emotionality, stress response, and reproductive functions in male and female 2045
2014 dopamine-transporter knockout mice. Behav. Pharmacol. 11 (3–4), 279–290. rats. Dev. Psychobiol. 51 (3), 259–267. 2046
2015 Stack, E.C., Numan, M., 2000. The temporal course of expression of c-Fos and Fos B van Ijzendoorn, M.H., Bakermans-Kranenburg, M.J., Mesman, J., 2008. Dopamine 2047
2016 within the medial preoptic area and other brain regions of postpartum female system genes associated with parenting in the context of daily hassles. Genes 2048
2017 rats during prolonged mother-young interactions. Behav. Neurosci. 114 (3), Brain Behav. 7 (4), 403–410. 2049
2018 609–622. van Leengoed, E., Kerker, E., Swanson, H.H., 1987. Inhibition of post-partum mater- 2050
2019 Stallings, J., Fleming, A.S., Corter, C., Worthman, C., Steiner, M., 2001. The effects of nal behaviour in the rat by injecting an oxytocin antagonist into the cerebral 2051
2020 infant cries and odors on sympathy, cortisol, and autonomic responses in new ventricles. J. Endocrinol. 112 (2), 275–282. 2052
2021 mothers and nonpostpartum women. Parent. Sci. Pract. 1, 71–100. Walum, H., Lichtenstein, P., Neiderhiser, J.M., Reiss, D., Ganiban, J.M., Spotts, E.L., 2053
2022 Stern, J.M., Johnson, S.K., 1990. Ventral somatosensory determinants of nursing Pedersen, N.L., Anckarsäter, H., Larsson, H., Westberg, L., 2012. Variation in the 2054
2023 behavior in the Norway rat: I. Effects of variations in the quality and quantity of oxytocin receptor gene is associated with pair-bonding and social behavior. Biol. 2055
2024 pup stimuli. Physiol. Behav. 47, 993–1011. Psychiatry. 71 (5), 419–426. 2056
2025 Stern, J.M., Kolunie, J.M., 1989. Perioral anesthesia disrupts maternal behavior dur- Wartella, J., Amory, E., Lomas, L.M., Macbeth, A., McNamara, I., Stevens, L., Lambert, 2057
2026 ing early lactation in Long-Evans rats. Behav. Neural Biol. 52 (1), 20–38. K.G., Kinsley, C.H., 2003. Single or multiple reproductive experiences attenuate 2058
2027 Strathearn, L., Fonagy, P., Amico, J., Montague, P.R., 2009. Adult attachment predicts neurobehavioral stress and fear responses in the female rat. Physiol. Behav. 79 2059
2028 maternal brain and oxytocin response to infant cues. Neuropsychopharmaco- (3), 373–381. 2060
2029 logy 34 (13), 2655–2666. Yang, J.-Y., Qi, J., Hang, W., Wang, F., Wu, Ch-F., 2010. Inhibitory role of oxy- 2061
2030 Swain, J.E., Lorberbaum, J.P., 2008. Imaging the human parental brain. In: Neurobi- tocin in psychostimulant-induced psychological dependence and its effects 2062
2031 ology of the Parental Brain. Academic Press, Burlington, MA, pp. 83–100. on dopaminergic and glutaminergic transmission. Acta Pharmacol. Sin. 31, 2063
2032 Takayanagi, Y., Yoshida, M., Bielsky, I.F., Ross, H.E., Kawamata, M., Onaka, T., Yana- 1071–1074. 2064
2033 gisawa, T., Kimura, T., Matzuk, M.M., Young, L.J., Nishimori, K., 2005. Pervasive Yu, G.Z., Kaba, H., Okutani, F., Takahashi, S., Higuchi, T., 1996. The olfactory bulb: a 2065
2034 social deficits, but normal parturition, in oxytocin receptor-deficient mice. Proc. critical site of action for oxytocin in the induction of maternal behaviour in the 2066
Natl. Acad. Sci. U.S.A. 102 (44), 16096–16101. rat. Neuroscience 72 (4), 1083–1088. 2067

Neuroscience & Biobehavioral Reviews Volume Issue 2013 (Doi 10.1016 - J.neubiorev.2013.04.004) OlazÃƒÂ¡Bal, D. Pereira, M. Agrati, D. Ferreira, A. Flem

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Neuroscience & Biobehavioral Reviews Volume Issue 2013 (Doi 10.1016 - J.neubiorev.2013.04.004) OlazÃƒÂ¡Bal, D. Pereira, M. Agrati, D. Ferreira, A. Flem

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Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx

Contents lists available at SciVerse ScienceDirect

Neuroscience and Biobehavioral Reviews

2 Flexibility and adaptation of the neural substrate that supports maternal

0149-7634/$ – see front matter © 2013 Published by Elsevier Ltd.

2 D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx

4.1. Comparative analysis of the neural basis of postpartum maternal behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

46 1. Introduction in some species like prairie voles, California mice, or marmosets, 88

55 displayed by females in different hormonal states and physiolog-

D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx 3

ers. Therefore, communal breeding systems can be an alternative to 208

cases of non-selectivity, and interspeciﬁc adoption in group-living 211

153 underground, as in many rodents and in rabbits, or at ground level,

Q3 (Denenberg et al., 1969; González-Mariscal and Rosenblatt, 1996;

(González-Mariscal and Poindron, 2002; Numan et al., 2006). How- 248

in both E2 and P4 levels during pregnancy followed by a decline 250

4 D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx

264 of maternal behavior in several species (Bridges, 1996). In early

266 monally primed rats facilitated the induction of maternal behavior.

308 that must be removed across pregnancy to resolve, at parturi-

310 towards the young.

D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx 5

to the evidence obtained by using immediate early gene expres- 480

sion, associated with different parental behaviors and conditions. 481

as immediate early genes, are activated in response to a variety 484

the Hypothalamus (AH/VMN) to inhibit maternal behavior in rats 502

6 D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx

Q5 the LS during parental behavior in voles (Kirkpatrick et al., 1994),

Q6 ate portion of LS (LSi) in maternal rats (Sheehan et al., 2000, 2002).

D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx 7

in this region altered the frequency, duration, and execution of 616

8 D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx

627 the IL subregion wanes, whereas additional mPFC subregions, such

657 (Stack and Numan, 2000), rabbits (González-Mariscal et al., 2009),

Q8 (Insel and Harbaugh, 1989; Numan and Corodimas, 1985). There

D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx 9

Q9 et al., 2008). Both mother and offspring frequency of vocalizations

10 D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx

exposures when the animal is already maternal (Kalinichev et al., 934

in maternal juveniles is adult-like at around 25–29 days of age 936

D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx 11

989 taneous parental behavior in voles, and in California mice, or in the

992 disrupt maternal behavior in rats (Corodimas et al., 1993; Felton

et al., 2008). 1080

explored maternal sensitivity and mothering in human mothers 1082

1027 always do because of the lack of information on the behavior of our

12 D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx

1113 associated with higher levels of affectionate contact and attraction

D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx 13

transporter) have been associated with different forms of parenting 1290

Q14 action. Bakermans et al. (2008) looked to a variant of the OXTR

1272 grooming, and on maternal postpartum depression. Although it behavior. 1338

1276 family, experience, and contextual background.

14 D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx

1362 provide information on the changes in neural substrate that support

1370 mediates some components of maternal behavior most commonly

1381 should be regulated differently in species with precocial young than

D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx 15

16 D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx

D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx 17

18 D. Olazábal et al. / Neuroscience and Biobehavioral Reviews xxx (2013) xxx–xxx

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