HYPOTHALAMUS The hypothalamus is a very small, but extremely important part of the diencephalon that is involved in the mediation of : endocrine, autonomic and behavioural functions.

General information Part of diencephalon Weighs about 4 grams The whole brain weighs 1 400 grams Occupies the bottom and infero-lateral walls of the 3rd ventricle

The Diencephalon Landmarks that are visible on the ventral and medial (ventricular) surfaces of the brain define the boundaries of the hypothalamus. The rostral boundary visible on the ventral surface of the brain is formed by the optic chiasm while the mammillary bodies define the posterior boundary. Between these structures the oval prominence from the floor of the third ventricle is the tuber cinereum and evaginating from this is the median eminence which then tapers into the infundibular stalk which together form the inferior boundary of the hypothalamus. On the medial (ventricular) surface of the brain other structures contributing to the rostral boundary that are visible include the lamina terminalis and the anterior commisure. Also visible on the medial surface of the brain is the hypothalamic sulcus, which is the rostral continuation of the sulcus limitans that defines the superior boundary of the hypothalamus. Finally, the internal capsule that is only visible on coronal or horizontal sections of the brain forms the lateral boundary.

The Diencephalon fornix thalamus Epithalamus (Pineal & hypothalamus Habenula) hypothalamus subthalamus Optic chiasm Mammillary body pituitary

Hypothalamus Hypothalamic sulcus Anterior commissure Lamina terminalis Mamillary body Optic chiasma

Hypothalamus Position: Boundaries 3. Superiorly: hypothalamic sulcus lies ventral to thalamus Boundaries Anteriorly: Lamina terminalis 2. Posterior: continues with midbrain tegmentum i iii ii 4. Inferiorly: i. optic chiasma,ii. tuber cinereum, infundibulum, and iii. mamillary body

Organization In the sagittal plane, it is customary to divide the hypothalamus into three regions: These are from medial (3rd Vent.) to lateral: Periventricular, Medial, and Lateral In the coronal plane, the hypothalamus can be divided into: 1.Anterior (supraoptic), 2. Middle (tuberal), and 3. Posterior (mammillary). Since in a deep plane the structures in in the SO region extend beyond the lamina terminalis, therefore the preoptic region is also included in hypothalamus

Divisions of the Hypothalamus

Three rostral to caudal regions are distinguished in the hypothalamus that correspond to three prominent features on its ventral surface: 1) The supraoptic or anterior region at the level of the optic chiasm, 2) the tuberal or middle region at the level of the tuber cinereum (also known as the median eminence—the bulge from which the infundibulum extends to the hypophysis), and 3) the mammillary or posterior region at the level of the mammillary bodies

Hypothalamus Chiasma opticum Infundibulum (median eminence) Tuber cinereum Mamillary body Optic tract 1 2 3 Ventral view

3rd Ventricle Medial Zone Lateral Zone Fornix Periventricular zone Preoptic, Supraoptic, Suprachiasmatic, Anterior, Paraventricular Anterior chiasmatic Dorsomedial Ventromedial Arcuate Nucleus Middle Tuberal 3rd Ventricle Fornix Periventricular zone Medial Forebrain Bundle Posterior Mamillary Caudal Mammilary

Hypothalamic Connections Receives indirect sensory inputs from all sensory systems Sends neural outputs to various motor control nuclei Sends neural outputs to sympathetic and parasympathetic nervous systems Sends both neural and hormonal outputs to pituitary

MAJOR CONNECTIONS OF HYPOTHALAMUS LIMBIC SYSTEM  1. MEDIAL FOREBRAIN BUNDLE septal nuclei, olfactory regions HYPOTHALAMUS & brain stem  2. FORNIX Hippocampal Complex Mammillary Bodies of Hypothalamus  3. STRIA TERMINALIS Amygdala Hypothalamus  4. MAMMILLOTHALAMIC TRACT Hypothalamus Thalamus (anterior nucleus)

ENDOCRINE CONNECTIONS AUTONOMIC CONNECTION  5. DORSAL (posterior) LONGITUDINAL FASCICULUS Hypothalamus Brain Stem Reticular Formation Hypothalamus Brain Stem Nuc (e.g. Vagus) Intermediolateral Cell Column ENDOCRINE CONNECTIONS  6. HYPOTHALAMOHYPOPHYSIAL TRACT Hypothalamus Neurohypophysis  7. Tuberoinfundibular Tract Tuberal Nuclei Sinusoids, Portal Veins Adenohypophysis

Hypothalamus Functions

The Hypothalamus Neural Influences Hormonal Influences Endocrine System Autonomic Nervous Limbic

Functions of the Hypothalamus Autonomic nervous system regulation Hormone production Endocrine regulation Circadian rhythm regulation Limbic system interaction Various Temperature regulation Feeding

Functions of the Hypothalamus Autonomic nervous system regulation Anterior area influences PSNS through projections to brainstem PSNS nuclei Posterior area influences SNS through projections to the lateral gray horn

Functions of the Hypothalamus Supraoptic and paraventricular nuclei produce oxytocin and vasopressin (ADH) Transported via axonal transport systems (hypothalamohypophysial tract) to neurohypophysis Released in circulation Clinical Correlate Damage to supraoptic n.  diabetes insipidus Hormone production

Functions of the Hypothalamus Endocrine regulation Stimulating or inhibiting hormones are transported via the tuberoinfundibular tract and released in to the pituitary portal system and ultimately to the adenohypophysis

Functions of the Hypothalamus Circadian rhythm regulation Input from retina to suprachiasmatic nucleus is then sent through poorly defined projections to the pineal gland

Functions of the Hypothalamus Limbic system interaction Preservation of species securing food, defense mechanisms, sexual behavior Emotions Affective behavior Memory Motivation Mammillary body

Functions of the Hypothalamus Various Temperature regulation Feeding Temperature Posterior n. conserves heat Anterior n. dissipates heat Fever starts – sweating Fever ends – chills Feeding Lateral n. induces eating Ventromedial n. inhibits eating

ADENOHYPOPHYSIS NEUROHYPOPHYSIS Connected with the hypothalamus via the hypophyseal portal system NEUROHYPOPHYSIS Connected with the hypothalamus via the hypophyseal tract

Tubero-infundibular tract

Posterior Pituitary Hormones Antidiuretic hormone (ADH) or vasopressin and Oxytocin synthesized primarily in the supraoptic nuclei & Paraventricular nuclei of the hypothalamus Hypothalamohypophysial tract

Anterior ( Supraoptic ) Region Preoptic Nucleus Control of parasympathetic function Supraoptic Nucleus Synthesis and secretion of vasopressin. Damage causes diabetes insipidus. Suprachiasmatic Nucleus Fibers from the retina; fibers to the pineal body. Controls circadian rhythms. Anterior Controls temperature and sexual behavior. Paraventricular Synthesis and secretion of oxytocin (milk secretion & uterine contraction). Controls food intake

Middle or Tuberal Dorsomedial Nucleus Ventromedial Nucleus - center of satiety - on stimulation rage, cruelty Ventromedial Nucleus - on stimulation depression of appetite Arcuate Nucleus - periventricular in tuber cinereum - secretes releasing-factors - dopaminergic neurons inhibit release of prolactin One important function that has been attributed to the ventromedial nucleus is control of eating. Bilateral lesions of the ventromedial nucleus in animals and probably humans as well, result in overeating (hyperphagia) and extreme obesity as well as a chronically irritable mood and increase in aggressive behavior (termed hypothalamic rage). By contrast,bilateral lesions in the lateral hypothalamic area result in anorexia (lack of appetite). Animals with lesions in this area may die of starvation. As a result of these lesion studies (along with supporting stimulation studies), the ventromedial nucleus has been referred to as a satiety center and the lateral hypothalamic area as a feeding center. SET POINT THEORY OF WEIGHT CONTROL

Posterior or Mamillary Region Mamillary Nucleus - impulses from hippocampal formation via fornix - impulses from tegmental nuclei, nuclei raphae via mamillary peduncle - projections to anterior thalamic nucleus via mamillothalamic peduncle Nucleus posterior - controls thermoregulation (preserving temperature and producing heat) - damage causes poikilothermia – inability of thermoregulation

Lateral zone 1. lateral preoptic Nucleus Clinical Correlate Crossed by Medial forebrain bundle Contains two nuclei: 1. lateral preoptic Nucleus 2. lateral hypothalamic Nucleus Clinical Correlate - when stimulated feeling of hunger - when destroyed anorexia nervosa and fast

Neurotransmitters in the Hypothalamus The hypothalamus has been referred to as a “pharmacological museum” by virtue of the plethora of neurotransmitters that it contains. The list of putative neurotransmitters includes: ACh, GABA, glutamate, serotonin, dopamine, and norepinephrine as well as literally dozens of peptides that have been identified in recent years.

SUMMARY Dorsomedial

MAJOR FIBER TRACTS OF HYPOTHALAMUS

Lesion of lateral hypothalamic area leads to starvation Lesions of VMN leads to morbid obesity

The hypothalamus is supplied with blood by small branches of the Circle of Willis

Diabetes Insipidus Damage to the anterior hypothalamus blocks the production of ADH, resulting in diabetes insipidus, which is characterized by rapid water loss from the kidneys.

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