Hypothalamus Functions PDF

Hypothalamic functions Oleg Osadchii 1  Overview of the brain structure. Anatomically, hypothalamus is part of diencephalon. 2 Physiologically, hypothalamus is part of the limbic system.  Functi...

Hypothalamic functions Oleg Osadchii 1  Overview of the brain structure. Anatomically, hypothalamus is part of diencephalon. 2 Physiologically, hypothalamus is part of the limbic system.  Function of hypothalamus  It monitors changes in internal and external environment, and maintains homeostasis.  Hypothalamus is well-suited to serve this function, for two reasons at least – (i) It contains circumventricular organs, which are devoid of the blood-brain barrier. (ii) It has extensive connections with other parts of the brain. 4  Circumventricular Other brain structures organs Circumventricular organs have fenestrated capillaries and hence are devoid of the blood-brain barrier. Overall, there are six CVO organs in the brain, of which three are located in the hypothalamus. OVLT is organum vasculosum of lamina terminalis.  Function of hypothalamus  It monitors changes in internal and external environment, and maintains homeostasis.  Hypothalamus is well-suited to serve this function, for two reasons at least – (i) It contains circumventricular organs, which are devoid of the blood-brain barrier. (ii) It has extensive connections with other parts of the brain. 7 Hypothalamus serves as a major integrating center..Pituitary gland. Endocrine system.  Connections of hypothalamus (i) Through connections with pituitary gland, hypothalamus controls major endocrine and reproductive functions. (ii) Through connections with brainstem, hypothalamus controls cardiovascular, respiratory, autonomic and thermoregulatory functions. (iii) Through connections with limbic system, hypothalamus controls emotions, sexual drive, etc. (iv) Through connections with cerebral cortex, it controls higher functions, such as learning and memory. 9  Medial Four groups of nuclei in the hypothalamus.  Functions of hypothalamus (i) Control of the autonomic nervous system. (ii) Production of hormones. (iii) Regulation of the emotional behavior. (iv) Regulation of feeding, hunger and satiety. (v) Regulation of thirst. (vi) Control of body temperature. (vii) Regulation of circadian rhythms. 11  Functions of hypothalamus (i) Control of the autonomic nervous system. (ii) Production of hormones. (iii) Regulation of the emotional behavior. (iv) Regulation of feeding, hunger and satiety. (v) Regulation of thirst. (vi) Control of body temperature. (vii) Regulation of circadian rhythms. 12 Centers for autonomic regulation are located at the different levels in the CNS. Hypothalamus is at the top position in this hierarchy. Hypothalamic nuclei that regulate activity of the autonomic nervous system. Regulation of the autonomic nervous system by hypothalamus.  Hypothalamus and autonomic nervous system  Stimulation of posterior hypothalamic nuclei results in sympathetic responses (increased heart rate, blood pressure, etc).  These effects are mediated via the hypothalamospinal tract which projects to the sympathetic neurons in the spinal cord.  Stimulation of anterior hypothalamic nuclei results in parasympathetic responses.  These effects are mediated via the hypothalamobulbar tract which projects to the nuclei of cranial nerves in the brainstem, and to the parasympathetic neurons in sacral spinal cord.  For its close links with regulation of autonomic function, Sherrington called hypothalamus “the head ganglion of ANS”. 16 Hypothalamus regulates responses to stress.  Functions of hypothalamus (i) Control of the autonomic nervous system. (ii) Production of hormones. (iii) Regulation of the emotional behavior. (iv) Regulation of feeding, hunger and satiety. (v) Regulation of thirst. (vi) Control of body temperature. (vii) Regulation of circadian rhythms. 18 Endocrine glands: Overview 19 Anatomy of the pituitary gland.  Small size Large size Two types of hypothalamic neurons that may secrete hormones (neurohormones). Magnocellular neurons Secretion of oxytocin and ADH by the hypothalamus. Parvocellular neurons in arcuate nucleus Parvocellular neurons have short axons. Hence these neurons communicate with anterior pituitary indirectly, by releasing hormones into the local capillary network. 23 Hormones secreted by the parvocellular neurons in the arcuate nucleus of hypothalamus 24  Medial Location of the centers for endocrine regulation within the hypothalamus.  Functions of hypothalamus (i) Control of the autonomic nervous system. (ii) Production of hormones. (iii) Regulation of the emotional behavior. (iv) Regulation of feeding, hunger and satiety. (v) Regulation of thirst. (vi) Control of body temperature. (vii) Regulation of circadian rhythms. 26 The Papez circuit. 27  Hypothalamus: Aggressive behavior Aggression is a type of hostile social behavior aimed at inflicting damage or harm on others. 28 Defensive aggression (left) is induced upon electrical stimulation of the medial hypothalamus (connected to periaqueductal gray matter), and predatory aggression (right: attacking the prey) is induced by stimulation of the lateral hypothalamus (connected to ventral tegmental area) in cats. Surgical resection of the cerebral hemispheres, either alone or with the anterior hypothalamus, causes a sham rage in cats. 31  Hypothalamus and aggression  In addition to its medial and lateral nuclei, the posterior part of the hypothalamus is also involved in generating the aggressive behavior.  In cats, surgical resection of the cerebral hemispheres, either alone or with the anterior hypothalamus, causes a behavioral reaction termed sham rage.  The sham rage includes autonomic and motor reactions associated with rage, such as increased heart rate and blood pressure, arching of the back, extended claws, and lashing of the tail. 32  Hypothalamus and aggression  The sham rage can be induced when the posterior hypothalamus is left intact during surgical resections of the cerebral hemispheres and the anterior hypothalamus.  These findings suggest that the posterior hypothalamus is particularly important for the expression of anger and aggression, and that normally it is inhibited by the cerebral cortex and the anterior hypothalamus. 33  Functions of hypothalamus (i) Control of the autonomic nervous system. (ii) Production of hormones. (iii) Regulation of the emotional behavior. (iv) Regulation of feeding, hunger and satiety. (v) Regulation of thirst. (vi) Control of body temperature. (vii) Regulation of circadian rhythms. 34  Medial Feeding center (lateral nucleus) and satiety center (ventromedial nucleus) in the hypopothalamus.  Neural factors in food intake  Two areas of hypothalamus involved in regulation of food intake are the feeding center and the satiety center.  Feeding center is located in the lateral hypothalamus. Its stimulation markedly increases food intake, whereas its destruction causes anorexia in animal studies.  Satiety center is located in the ventromedial hypothalamus. Its stimulation causes cessation of eating, whereas its lesion causes severe hyperphagia leading to morbid obesity. 36  Feeding center (lateral nuclei) Satiety center (ventromedial GIT hormones nucleus) Nutrients Reciprocal relationships of the feeding center and satiety center. Feeding center stimulates eating, which induces stomach distension and release of GIT hormones and nutrients into the blood. This activates the satiety center which stops feeding. Prolonged fasting induces hypoglycemia and ghrelin release into the blood, which stimulate feeding center. Control of the food intake. Five hormones released in the periphery may cross the BBB and act on the feeding center in hypothalamus. Mechanism of action of leptin. Note it can cross the BBB.  Leptin  Leptin is the key hormone in regulation of food intake and body weight. It is released by fat cells (adipocytes) into the blood.  The receptors for leptin are located in the arcuate nucleus of hypothalamus.  By stimulating these receptors, leptin decreases food intake, and promotes fat catabolism.  These effects are mediated through release of the melanocyte-stimulating hormone, which reduces appetite. 40  Ghrelin  Ghrelin is a peptide released into the blood from empty stomach, e.g. during fasting.  Ghrelin stimulates appetite, meaning it is acting antagonistically to leptin.  Receptors to ghrelin are located in the arcuate nucleus of hypothalamus.  Receptor stimulation by ghrelin results in increased secretion of neuropeptide Y, which stimulates appetite. 41 Interaction of leptin and ghrelin in regulation of food intake.  Metabolic factors and food intake  Plasma glucose concentration. Upon food ingestion, plasma glucose levels are increased. Glucose then increases activity of neurons of satiety center. This inhibits the feeding center, thus inhibiting food intake (the glucostatic hypothesis of regulation of food intake). In contrast, hypoglycemia stimulates food intake.  Plasma amino acids and fatty acids absorbed from GIT give rise to satiety and inhibit food intake. 43  Functions of hypothalamus (i) Control of the autonomic nervous system. (ii) Production of hormones. (iii) Regulation of the emotional behavior. (iv) Regulation of feeding, hunger and satiety. (v) Regulation of thirst. (vi) Control of body temperature. (vii) Regulation of circadian rhythms. 44  Medial Location of the thirst center within the hypothalamus. Regulation of thirst.  Thirst  The major factor inducing thirst sensation is increased blood osmolarity (even by as small as 1-2%) due to dehydration (e.g. severe sweating, vomiting, diarrhea).  Thirst is also stimulated by reduced blood volume, but only by a large blood loss (15-20%).  The thirst sensation is reinforced by dryness of the mouth and throat, which is caused by reflex decrease in saliva secretion in a water-deprived person.  The GI tract monitors water intake. Moistening of the mouth or distension of the stomach by water inhibits thirst, preventing excessive water intake. 47 Organum vasculosum and subfornical organ within the hypothalamus contain osmoreceptors. Circumventricular Other brain structures organs Hypothalamus contains circumventricular organs, which have fenestrated capillaries and hence are devoid of the blood-brain barrier. When the thirst center is stimulated, a signal is sent to the paraventricular nucleus to increase production of ADH. When ADH is released into the blood, it increases water reabsorption in kidney, which helps to conserve water in the body, and bring blood osmolarity back to normal.  Functions of hypothalamus (i) Control of the autonomic nervous system. (ii) Production of hormones. (iii) Regulation of the emotional behavior. (iv) Regulation of feeding, hunger and satiety. (v) Regulation of thirst. (vi) Control of body temperature. (vii) Regulation of circadian rhythms. 52 Hypothalamus monitors changes in blood temperature. Hypothalamic nuclei involved in regulation of body temperature. Regulation of body temperature by the hypothalamus.  Hypothalamus and body temperature  Anterior hypothalamus activates mechanisms that promote heat loss through cutaneous vasodilation and sweating, which decreases body temperature.  Posterior hypothalamus activates mechanisms that increase heat production through muscle shivering, and heat conservation through cutaneous vasoconstriction and piloerection. 56 Role of anterior and posterior hypothalamus in maintaining the set-point for body temperature.  Functions of hypothalamus (i) Control of the autonomic nervous system. (ii) Production of hormones. (iii) Regulation of the emotional behavior. (iv) Regulation of feeding, hunger and satiety. (v) Regulation of thirst. (vi) Control of body temperature. (vii) Regulation of circadian rhythms. 58  Hypothalamus and circadian rhythms  Circadian rhythm means 24 hours fluctuation in body functions (aka day-night variation or light-dark cycle).  Many body functions show a circadian pattern, e.g. sleep habit, corticosteroid secretion by adrenal gland, variation in body temperature, and melatonin secretion.  Most of these functions are regulated by hypothalamus. 59 Circadian rhythm in body temperature – it is lowest in early morning and peaks late afternoon. Circadian rhythm in cortisol secretion by adrenal gland – it is lowest during sleep and peaks shortly after awakening. Circadian rhythm in secretion of the growth hormone by the anterior pituitary. Circadian sleep-wake cycle.  Medial Location of the ciradian rhythm center within the hypothalamus. Suprachiasmatic nucleus is located just above the optic chiasm. It detects light and synchronizes daily biological and behavioral rhythms to the onset of light from the environment. Daily variations in electrical activity monitored in 100 individual neurons from the suprachiasmatic nucleus. Connections of the suprachiasmatic nucleus with different parts of the brain.  Functions of hypothalamus (i) Control of the autonomic nervous system. (ii) Production of hormones. (iii) Regulation of the emotional behavior. (iv) Regulation of feeding, hunger and satiety. (v) Regulation of thirst. (vi) Control of body temperature. (vii) Regulation of circadian rhythms. 68 Other functions of hypothalamus 69  Hypothalamus and reproductive function  Hypothalamus secretes gonadotropin-releasing hormone (GnRH) that plays crucial role in reproductive function and sexual behavior.  Its secretion starts in puberty and then continuous throughout the reproductive life, both in males and females. 70  Hypothalamus and sleep  Posterior part of hypothalamus is involved in regulation of sleep.  Stimulation of preoptic area of hypothalamus induces sleep.  Hypothalamus controls sleep by regulating the circadian rhythm. 71