The Hypothalamus: a sampler of function

Adrienne K. Salm Suggested reading: to

supplement lecture
4046-HSC-N only: Nolte Chapter 23;
asalm@hsc.wvu.edu pg 580-594 (579-593)

304-293-2435
Objectives
After completing the hypothalamus unit the well-informed student will be able to:
Describe the role of the hypothalamus as the integrator of diverse information and its ability to
initiate homeostatic responses.

Describe the relative location and function of key hypothalamic nuclei (supraoptic,
suprachiasmatic, paraventricular, preoptic, ventromedial dorsomedial, arcuate, mammillary
bodies, bed nucleus of the stria terminalis).

Recognize on sections: mammillary bodies, dorsal longitudinal fasciculus, mammillothalamic

tract, supraoptic nucleus (Haines atlas).

Understand the data supporting a biological basis for sexuality, sexual preference and gender
identity.

Covered by Dr. Lambert:

Describe the hypothalamus role as the head ganglion of the ANS.
Describe the basis for Horners syndrome findings.
Covered in Physiology
The hypothalamo-adrenal-pituitary (HPA ) axis
Hypothalamus: Anatomy

Boundaries
1. Ventral - optic chiasm, infundibulum

2. Posterior - mammillary bodies

3. Anterior - lamina terminals, preoptic/INAH area, septum

4. Superior - hypothalamic sulcus

5. Lateral - optic tract

Functions
1. Integration

2. Coordination

It packs a big punch for just ~4 g of tissue (vs. ~1400 g for the entire brain).
The hypothalamus plays a pivotal role in drive-related behaviors.

Nolte Fig. 23-2

The hypothalamus integrates information from diverse sources

2. Endocrine
1. Visceral Information
Information

Hypothalamus

3. Homeostatic 4. Cognitive -
Information Affective
5. Sensory Information
Information
 1. Visceral Information for example, comes to the hypothalamus
from the baroreceptors in the aortic arch and carotid bodies. They sense
variation in blood pressure and transmit this information to nucleus
solitarius which in turn projects to the hypothalamus. This is but one
example; input also from other viscera, e.g. gut.
Visceral Afferents
via IX,IX inf. ganglia

Nucleus of Solitary Tract

Hypothalamus
(Paraventricular Nucleus)

DMNX

Terminal ganglia of Heart Heart rate

 2. Endocrine Information arrives to the hypothalamus from all
endocrine glands via the blood.

Examples: thyroxine (thyroid), cortisol (adrenal cortex).

Receptive neuroendocrine cells

Releasing or inhibitory factors

Pituitary gland

Circulating hormone levels are detected by receptors on hypothalamic cells (blood-

brain barrier is deficient here). These cells secrete releasing factors or inhibitory
factors that pass down the portal system to control secretion of other peptides from
the anterior lobe of the pituitary.
3. Homeostatic Information arrives
via the Blood: Examples include
glucose,
osmolarity,
temperature,
and lipids

Hypothalamic
Internal
Sensing System
neurons Fig. 23-7 Nolte
4. Cognitive - Affective Information arrives through projections from
Frontal, orbitofrontal and cingulate cortices
and amygdala

Diverse Hypothalamic Areas

Autonomic and somatic motor systems: behavioral and autonomic manifestation

Fight, Flight, Fear, orFrolicking
 5. Sensory Information enters both directly and indirectly

Retinal afferents (direct);

Reticular activating system
(indirect)

Suprachiasmatic nucleus
Ventrolateral preoptic nucleus

Sleep Wake cycle

Alertness

Arousal, release of stereotypic behaviors (4 Fs)

The hypothalamus coordinates responses via its diverse outputs

An example: response to decreased blood volume (hypovolemia)

Hypothalamus

Regulates Internal Regulates External

Environment Environment
1. Regulates ANS
4. Initiates behaviors
e.g., vasoconstriction
e.g., drinking
2. Controls Endocrine Function
e.g., vasopressin release
Net Result: Homeostasis
3. Controls Motivational State
e.g., thirst
Anatomy
The hypothalamus has a medial and a lateral zone or area, and
each is divided rostrocaudally into
Anterior
Tuberal
Posterior
hypothalamic areas. There is also a thin periventricular layer.
Nissl stains form the basis of hypothalamic anatomical diagrams w
nuclei are identified.
Fig. 23-4 Nolte

Because of the tight packing of the nuclei, closed head injuries,

brain surgery, meningitis, encephalitis, strokes, subarachnoid
hemorrhages and neoplasms can all present as a constellation
of disturbances, depending on which nuclei are affected.
A sampler of interesting hypothalamic functions
The medial preoptic nucleus plays a role in the tendency to
approach, court, mate with, and partner with others.
Preoptic Nuclei. This area control behaviors necessary for the
propagation of the species including a large repertoire of reproductive
and maternal behaviors. Its development is under control of
testosterone during critical periods. It has different structural and
functional characteristics in males vs. females. Hence it is sexually
dimorphic.

In rats, Gorski et al., demonstrated in the late 70s that rat partner preference,
and repertoire of copulatory behaviors are related to the structure of the POA.
Beginning with the work of Gorski, it was discovered in the late 70s that
the development of sexual characteristics and later sexual behaviors
could be experimentally manipulated in rats by strategic exposure to
testosterone during development.

Adult sexual behavior in the rat depends on whether the brain was
organized by gonadal hormones during the first few days after
birth.
 The POA SDN is larger in males than females
Females androgenized with a testosterone proprionate (TP) injection on
day 4 have significantly larger SDN volume than control (oil-treated )
females
SDN volume is reduced in males castrated on day 1 compared with
normal males (Gorski, 1980)
 Summary of MPOA and INAH nuclear development
These nuclei are sexually dimorphic, i.e., they develop and function
differently in males vs. females

The development of the POA is under the control of circulating androgens

during development. Females rats have smaller POA nuclei than males:
fewer neurons and smaller dendritic arbors. Males that have been castrated
at birth develop female-like POA nuclei. Females that are given testosterone
at a critical period develop male-like POA nuclei.

Since then it has been established that sexual behaviors in many species are
under the control of the POA.

Sexual behaviors and preferences are highly correlated with the size of the
POA.

The Interstitial Nucleus of the Anterior Hypothalamus is the human analog of

the POA in rodents and similar data have been gained in humans at this
time.
Closer to home The MPOA in primates

Oomura et al., 1983. Central Control of Sexual Behavior. Brain Res.

Bulletin (20)863-870
Male primate preoptic area neurons fire before and during sexual
encounters.
Female primate MPOA responsiveness occurs prior to that of
the male

Single MPOA neuron activity during copulatory presenting.

Female monkey. Increase in activity at prepresenting phase and
decrease in activity at presenting phase. Upper, raster display of
neuron discharge. Lower, histogram of neuron activity. Arrow,
onset of presenting.
Soooo what about humans?? The third interstitial nucleus of the anterior
hypothalamus appears to be the human homolog to the sexually dimorphic
preoptic area in rodents.

3
 A Difference in Hypothalamic Structure Between
Heterosexual and Homosexual Men
Simon LeVay
(confirmed 1989 Allen and Gorski findings)

The anterior hypothalamus of the brain participates in the regulation of

male-typical sexual behavior. The volumes of four cell groups in this
region [interstitial nuclei of the anterior hypothalamus (INAH) 1, 2, 3,
and 4] were measured in postmortem tissue from three subject groups:
women, men who were presumed to be heterosexual, and homosexual
men. No differences were found between the groups in the volumes of
INAH 1, 2, or 4. As has been reported previously, INAH 3 was more
than twice as large in the heterosexual men as in the women. It was also,
however, more than twice as large in the heterosexual men as in the
homosexual men. This finding indicates that INAH is dimorphic with
sexual orientation, at least in men, and suggests that sexual orientation
has a biological substrate.

Salk Institute for Biological Studies, San Science, 1991; Vol.253

Diego, CA 92186
 http://www.simonlevay.com/Home?pli=1

This website presents extensive

pro and con
data pertaining to he issue of
whether there is a biological basis
for sexual orientation.

INAH 3 found to be larger in heterosexual men

Steroid sensitive neurons are distributed throughout the hypothalamus and
brain and likely account for the array of gender-preferred behaviors seen in
animals and humans.

John L. Gill: All biological variables are distributed normally . Author of

Design and Analysis of Experiments in the Animal and Medical Sciences. Vols I and II.
Heterosexuality: Activation of the hypothalamus correlates strongly with the degree of
heterosexual sexual identity in males watching erotic vs. sports video clips of heterosexual
encounters
Those students who self-identified as male most strongly had higher

BOLD signals and these were strongest in the bilateral anterior

hypothalamus.
 Gender Identity: (the conviction of belonging to the
male or female gender). Is it nature or nurture?
Some boys in the
Dominican Republic
are identified and
raised as girls until
puberty.
These individual lack 5-a-
reductase or 17B-hydroxy-
steroid-dihydrogenase which
prevents peripheral
testosterone from being
converted to
dehydrotestosterone.

At puberty androgen
production increases and they
become externally
masculinized. Anecdotal data
indicate that 60% make the
transition into teenage boys
with little fanfare.
 A disastrous tale of nurture vs. nature: Bruce
becomes Brenda
Each of us has a gender identity - a private feeling that we are male or
female. There are two fundamentally different explanations for how this
develops.

A (previously) influential theory is that our gender identity is the result of

environmental influences, particularly the way we are treated by our parents,
guardians, friends and relatives. According to Dr John Money we are
psychosexually neutral at birth, and our gender is a consequence of the
nurture we receive as children.

Another view is that gender may is the result of nature, particularly the
effects of hormones on the developing brain.

This is not a dry academic argument. The lives of a significant number of

people have been changed as a result of the application of these theories.
Brenda Reimer
David Reimer
Transgenderism
Many individuals choose to change their gender identity. Is this a case of when the
hypothalamus doesnt match the exterior phenotype?
The INAH3 and 4 (uncinate nucleus) was found in male-to-female transsexual
people to be small (of female size and number). One case in the other direction
so far finds a female to male transexual INAHS to be larger (male-sized).
A Sex Difference in the Human Brain
and its Relation to Transsexuality.
J.-N. Zhou, M.A. Hofman, L.J. Gooren and
D.F. Swaab
Int. J. Transgenderism 1 (1) 1997

HeteroM HeteroW

Sexual identity vs. preference

The bed nucleus of the stria terminalis

(as visualized by VIP innervation) is
more female-like in a male to female
transsexual. HomoM Male to female
transsexual
 For more information

http://transascity.org/the-transgender-brain/

ALso

Also see publications by Roger Gorski

 Brain Jokes

What did the right hemisphere say to the left hemisphere

when they could not agree on anything?

Let's split."

What happens if you break the brain scanner?

You will have a CATastophe.

What kind of fish performs brain operations?

A neurosturgeon.
Supraoptic Nucleus (SON)

Located in the anterior and medial zones

bilaterally adjacent to optic chiasm

Receives afferents from the brainstem with information

about uterine distension, nipple suckling, blood volume.

Sends axons to the posterior pituitary

Produces oxytocin and vasopressin

Functions: osmosensitivity, water balance, blood volume

regulation, lactation, milk ejection,
orgasm, maternal behaviors

** Lesions lead to diabetes insipidus

with polyuria and polydipsia

**SIADH (syndrome of inappropriate ADH release

resulting in hyponatremia and fluid overload.
Due to tumors, stroke, encephalitis)
Oxytocin: The love peptide

It keeps couples together

ARTICLE
Oxytocin enables maternal behaviour by
balancing cortical inhibition
Marlin et al., Nature 14402

Helps parents still like their kids and vice versa

Oxytocin: The love peptide

Gigi

Gizmo

It even plays a role in dog-human bonding

Paraventricular Nucleus (PVN)

Bilaterally adjacent to third ventricle in the anterior and medial

zones

Receives afferents from brainstem (n. solitary tract) concerning

blood volume, suckling, cortisol levels

Efferents to:

brainstem and spinal cord - autonomic regulation

median eminence - corticotropin releasing factor

posterior pituitary - oxytocin, vasopressin

Functions:
produces oxytocin and vasopressin
osmosensitivity: water balance, blood volume
regulation, lactation, milk ejection,
stress response

** Lesions lead to diabetes insipidus with polyuria and

polydipsia

**SIADH-Syndrome of inappropriate secretion of ADH

 Suprachiasmatic nucleus (SCN)
Afferents: peripheral retinal ganglion cells concerned with luminance.
Also neurons have melatonin receptors.

Efferents: output reaches pineal (via PVN?) to IML cell

column to SCG to pineal

Functions: entrains circadian rhythms of sleeping,

eating, melatonin synthesis
The SCN entrains pacemakers throughout the body
 Our free-running sleep cycle is about 25.3
hours
Human
Hamster in constant light

SCN
lesioned
bilaterally
Bedtime self
selected at day 20
 Pineal: site of melatonin synthesis

SCN
Melatonin is a popular OTC cure for jet lag
A PVN-Pineal Projection via the Stria medullaris thalami-Who knew?!!
Also related to daily rhythms
The lateral preoptic nucleus also receives afferents from
peripheral retina ganglion cells concerned with luminance.

Sends projections to monoaminergic cells

involved with arousal and sleep.

May be the means by which light levels

regulate sleepiness
The hypothalamus plays a pivotal role in feeding behavior (Nolte pg. 594)

The Ventromedial nucleus: lesions result in overeating and obesity, (putative

satiety center).

The Lateral Hypothalamic Area: lesions result in undereating (putative

feeding center).

The Arcuate nucleus receives nucleus tractus solitarius

Information about stomach distension. Contains receptors for leptin (from
adipocytes; signals satiety) and ghrelin (stimulates feeding).
The Anterior and Preoptic Hypothalamic areas (cooling system): stimulation here
lowers body temperature through:

vasodilation
increase in panting/respiration

The Posterior Nucleus (heating system:) stimulation here increases body

temperature through:
vasoconstriction
shivering

These two centers

reciprocally feedback to
each other.
The Mammillary Bodies: Limbic System Component
Memory consolidation
Korsakoffs Psychosis (along with anterior thalamic nucleus)
Susceptible to thiamine deficiency
Hypothalamus Labwork

Nissl stained nuclei

Pathways in and out
 Created by John I. Johnson, Ph.D. Michigan State University
http://www.msu.edu/user/johnso48/552/hypothalamus/page02.html
Tracts: mammillothalamic and fornix

Haines 7-2
Tracts: mammillothalamic and fornix

Haines 7-4
The Dorsal Longitudinal Fasciculus
The Medial Forebrain Bundle
Basal olfactory region
orbitofrontal cortex
entorhinal cortex
septal nuclei

Hypothalamus

Brainstem nuclei
Periaquaductal grey
Dorsal motor X
Review slides for your edification.
ADH and oxytocin are
secreted by
hypothalamus and
carried in axons to
posterior lobe for
direct release.
ADH water retention Supraoptic and
by kidney paraventricular
nuc.

Oxytocin milk let-

down and uterine
contraction, maternal
behaviors, orgasm
 This is the basic
plan for control of
all the anterior lobe
hormones:
releasing factors or Portal
inhibitory factors system
are released to the
portal system for
transport to
anterior lobe.
There they act on
secretory cells.

Endocrine target organs

Hormones of the pituitary
Review physiology as necessary
Control of the Autonomic Nervous System

The Hypothalamus as Head Ganglion of the ANS

Sympathetic - Lateral and Posterior Hypothalamus
- dilated pupils
(EXCITED) - piloerection
- vasoconstriction
- increased heart rate
- increased respiration
- decreased gut and bladder motility
- rage reaction, Fight or Flight

Parasympathetic - Anterior and Medial Hypothalamus

- decreased heart rate
(RELAXED) - increased gut motility
Horners Syndrome
* Injury to cervical sympathetic system /
reticular formation /
peripheral sympathetic pathway

* Miosis: (constricted pupil) paralyzed

dilator muscle

Ptosis of eyelid: (droopy eyelid) paralyzed

superior tarsal muscle (Mllers)

Enopthalmos: (sunken eye) paralyzed

orbitalis muscle (Mllers)

* Anhydrosis: (absence of sweating)

* Vasodilation
Horners syndrome cont.
The lateral hypothalamus projects to
sympathetic centers in the lateral medulla. There
are also descending hypothaamospinal
connections directly to the IMLCC.