Neurosciences: Hypothalamus March 10, 2010 1. Identify the hypothalamus and its anatomical boundaries a.

Rostral: optic chiasm b. Caudal: mammillary bodies c. Middle: i. Tuber cinereum: bulge of tissue between optic chiasm and mammillary bodies ii. Infundibulum: connects hypothalamus w/ pituitary gland d. Dorsal: thalamus 2. Recognize the major subdivisions of the hypothalamus according to specific landmarks. a. Anterior to posterior i. Preoptic/Anterior: rostral 1. Landmark: optic chiasm ii. Middle: tuberal region 1. Landmark: tuber cinereum iii. Posterior: mammillary 1. Landmark: mammillary stalk b. Sagittal (using fornix) i. Lateral: lateral to the fornix ii. Medial: medial to the fornix iii. Periventricular: immediately adjacent to and surrounding the 3 rd ventricle 3. Identify the few hypothalamic nuclei that are visible in conventionally stained histological sections, and locate the general hypothalamic areas that are associated with specific hypothalamic functions

a. 4. List the general functions of the hypothalamus a. Homeostasis b. Endocrine control c. Autonomic nervous system control (upper motor neurons for the ANS) d. Limbic mechanisms (emotion and memory) 5. List the specific functions that have been defined for specific hypothalamic nuclei or areas General Hypothalamic Function
Control of Body Temperature

Nucleus

Specific Role

Anterior Hypothalamic Area Posterior Hypothalamic Area

Detects increase in body T stimulates ANS to dissipate heat via sweating, panting, skin vasodilation Detects decrease in body T stimulates ANS to conserve heat (skin vasoconstriction) and produce it (shivering, increasing body metabolism) SCN receives projections from retinal ganglion cells via retinohypothalamic tract SCN synapses w/ sub-paraventricular zone symp/pre neurons that control melatonin release from pineal gland AT NIGHT melatonin feeds back on SCN to modulate circadian rhythms and sleep

Control of Circadian Rhythms

Suprachiasmatic Nucleus (SCN)

Sleep and Arousal

Histamine neurons in tuberomammillary region & hypocretin neurons of lateral hypothalamic region Galanin/GABAergic neurons in ventrolateral preoptic area

Generate behavioral arousal and wakefulness *Antihistamines: sedating *Coma: lesion in posterior hypothalamus *Narcolepsy: loss of hypocretin neurons

Responsible for the generation of slow wave sleep by inhibiting brainstem monoaminergic neurons involved in behavioral arousal *Insomnia: lesion in anterior hypothalamus Make ADH and oxytocin in magnocellular cells; hormones stored in posterior pituitary high blood osmolarity: increase ADH to stimulate water reabsorption in kidneys low blood osmolarity: vv. Synthesize releasing and inhibiting hormones that control the release of hormones from the pituitary gland

Regulation of Fluid Balance

Supraoptic Nucleus (SON) and Paraventricular Nucleus Preoptic and anterior hypothalamic nuclei Ventromedial Nucleus Lateral Hypothalamic Area

Control of Pituitary Endocrine Function Control of Feeding

Satiety Center Produces satietylesions cause overeating Hunger Center Produces feeding via stimulation of LH neurons and dopaminergic axons in the medial forebrain bundle Lesions cause satiety (anorexia, weight loss)

Arcuate Nucleus

Next to VMH Controls appetite, especially satiety Contains peptides for leptin (satiety signal sent to POMC) and ghrelin (hunger signal sent to NPY) *Insulin inhibits ghrelin receptor (insulin resistance = more ghrelin?)

6. Trace significant hypothalamic connections with other CNS structures, and identify those that are readily visible in histological sections. Tract
Mammillotegmental Tract (MTegT)

Direction
To and from midbrain tegmentum

Type
Sympathetic

Function
Central for controlling the ANS

Dorsal Longitudinal Fasciculus (DLF)

To and from parasympathetic nuclei in brainstem and spinal cord To and from brainstem tegmentum

Parasympathetic

Central for controlling the ANS

Medial Forebrain Bundle (MFB)

Axons of dopamine neurons transverse MFB/LH from the substantia nigra to the caudate, and from ventral tegmental dopamine neurons to amygdala, septum, prefrontal and cingulate cortices.

Essential tract for reward, reinforcement, and pleasure

Mammillothalamic Tract (MTT)

Connects mammillary nuclei and anterior thalamic nuclei (emotional circuitry) From the hippocampus to the mammillary bodies

Integration of mood, drives, and emotions leads to ANS physiological states) Memory formation involving hippocampus and mammillary nuclei Memory formation

Fornix

Function Temperature regulation

Afferents from Cutaneous cold receptors; temperature-sensitive cells in hypothalamus

Integrating Areas Anterior hypothalamus (response to heat), posterior hypothalamus (response to cold) Dorsomedial and posterior hypothalamus Supraoptic and paraventricular nuclei Supraoptic and paraventricular nuclei Dorsomedial nuclei and neighboring areas Paraventricular nuclei

Neuroendocrine control of catecholamines Vasopressin Oxytocin Thyroid-stimulating hormone (thyrotropin, TSH) via thyrotropinstimulating hormone (TRH) Adrenocorticotropic hormone

Emotional stimuli, probably via limbic system Osmoreceptors, volume receptors, others Touch receptors in breast, uterus, genitalia Temperature receptors, perhaps others

Limbic system (emotional stimuli); reticular

Function (ACTH) and -lipotropin (

Afferents from formation ("systemic" stimuli); hypothalamic or anterior pituitary cells sensitive to circulating blood cortisol level; suprachiasmatic nuclei (diurnal rhythm)

Integrating Areas

-LPH) via corticotropinreleasing hormone (CRH)

Follicle-stimulating hormone (FSH) Hypothalamic cells sensitive to estrogens; eyes, and luteinizing hormone (LH) via touch receptors in skin and genitalia luteinizing-hormone-releasing hormone (LHRH) Prolactin via prolactin-inhibiting hormone (PIH) and prolactinreleasing hormone (PRH) Growth hormone via somatostatin and growth-hormone-releasing hormone (GRH) "Appetitive" behavior Thirst Hunger Touch receptors in breasts, other unknown receptors Unknown receptors

Preoptic area, other areas

Arcuate nucleus, other areas (hypothalamus inhibits secretion) Periventricular nucleus, arcuate nucleus Lateral superior hypothalamus Ventromedial satiety center, lateral hunger center; also limbic components Anterior ventral hypothalamus plus (in the male) piriform cortex In limbic system and hypothalamus Suprachiasmatic nuclei

Osmoreceptors, subfornical organ "Glucostat" cells sensitive to rate of glucose utilization

Sexual behavior

Cells sensitive to circulating estrogen and androgen, others Sense organs and neocortex, paths unknown Retina via retinohypothalamic fibers

Defensive reactions Fear, rage Control of various endocrine and activity rhythms

Hypothalamus

A.

Overview 1.

Connects with forebrain (particularly limbic areas), brainstem, and spinal cord 2.

With brainstem, contain suprasegmental integrating centers for autonomic, vegetative, emotional, and endocrine functions

B.

Function of regions and nuclei 1. Anterior region a. Anterior nucleus: maintenance of body temperature b.

Lateral hypothalamic nucleus: feeding center c.

Preoptic area (lateral and medial preoptic nuclei): blood volume, temperature, and reproductive activity d.

Paraventricular and supraoptic nuclei: release of oxytocin (for contraction of uterus and ejection of milk) and vasopressin (for water balance) e.

Suprachiasmatic nucleus: circadian rhythms

2.

Infundibular region a. Dorsomedial: emotional behavior

Stimulating the dorsomedial infundibular region causes aggressive behavior (sham rage) in experimental models.

b. Ventromedial: satiety center c. Lateral hypothalamic nucleus: feeding center

d.

Tuberal nuclei ( arcuate and infundibular nuclei) (1)

Produce releasing factors that regulate hormone release from anterior pituitary (2)

Releasing factors are transmitted to anterior pituitary through the hypophysial portal system (3) Clinically relevant releasing factors: corticotropin releasing factor, thyrotropin releasing factor, growth hormone releasing factors, prolactin releasing factor, gonadotropin releasing factor, and melanocyte stimulating hormone releasing factor

Korsakoff psychosis: degeneration of the mammillary bodies and severe anterograde and retrograde amnesia

3. Posterior region a. Mammillary nuclei: limbic function

Korsakoff psychosis, resulting from thiamine deficiency related to chronic alcoholism, is associated with anterograde and retrograde amnesia and with degeneration of the mammillary bodies and the dorsomedial nucleus of the thalamus. b. Lateral hypothalamic nucleus: feeding center

c. Posterior nucleus: blood pressure, emotional, maintenance of body temperature and analgesic functions

1. Compare neuroendocrine neurons vs normal neurons of the CNS. Neuroendocrine neurons release synaptic contents near capillaries in median eminence. They are similar to neurons in all respects, except they do not synapse on neurons. They release into hypothalamic-hypophyseal portal system. 2. List the major neural and endocrine inputs to the hypothalamus. Sensors throughout the body that determine when the body is out of homeostasis tell the hypothalamus to which sends signals to the body to change. Examples: Decrease or increase in colume of extracellular fluid or osmolality of extracellular fluid, change in body temperature, decreased or increased blood glucose, inputs from olfactory, visual and somatosensory 3. Describe neuroendocrine systems regulated by the hypothalamus, and their key functions 4. Identify behaviors and homeostatic regulatory mechanisms under hypothalamic control 5. Summarize the principal neural projections of the hypothalamus.

System/Behavior Male Sexual and Parental behavior Female Sexual behavior Thirst Aggressive behavior Heat Loss Heat Gain Milk Release and Uterine Contraction Water Balance

Nucleus/Nuclei MPOA (Medial Preoptic Area) VMH (Ventromedial nuc) MePO (Median preoptic nuc) AHA (Anterior Hypothal. Area) MPOA and AHA PN (Posterior Nucleus) PVN and SON (Paraventricular nuc. and supraoptic nuc.) PVN and SON

Functions GnRH neurons gonadal functions in male/female Input from olfactory, visual, somatosensory and amygdale Projects to other hypothalamic nuc for motivation and reward Input: Estrogen receptors, somatosensory informat from pudendal area Inputs: extra cellular fluid volume, osmolality Inputs: amygdale, sensory systems, testosterone receptors Inputs: blood temp Outputs: sweating, peripheral vasodilation Input: Low blood temp Output: shivering, piloerection, peripheral vasoconstriction Project to spinal sympathetic neurons Magnocellular neurons release oxytocin Amplified byposterior pituitary Oxytocin promotes pair-bonding and social interaction Magnocellular neurons release vasopressin water retention Diabetes insipidus cuased by lack of vasopressin

Stress Circadian rhythms Ingestive Behavior and Satiety

PVN SCN (Supraciasmatic nuc.) VMH and ARC (Arcuate nuc)

Parvicellular neuroendocrine neuros regulate anterior pituitary secretion of CRH and TRH cortisol secretion and thyroid reg. Input: retinal to extrain endogenous rhythms of activity Output: Secretion of melatonin from pineal gland ARC input: hunger, satiety and metabolism from leptin, insulin, glucose and fat VMH input: metabolic state from ARC ARC output: prolactin and GH secretion from anterior pituitary

7. Give examples of hypothalamic dysfunction. a. Lesions are usually bilateral b. Tumors and vascular insults are most common causes of dysfunction c. Associated symptoms with lesions in hypothalamic region i. Eye problems: compression of optic nerve ii. Sleep problems: compression of SCN iii. Chronic insomnia/severe hyperthermia: lesion in anterior hypothalamus affects ventrolateral preoptic area and anterior hypothalamic area, respectively iv. Coma/severe hypothermia: lesion in posterior hypothalamus affects tuberomammillary/lateral hypothalamic areas and posterior hypothalamic areas, respectively v. Narcolepsy: loss of hypocretin neurons (due to some environmental toxin) vi. MTegT: Horners syndrome