hypothalamus 1 papez circuit physiology .pptx

hypothalamus ppt

1. Neuropeptide Y Neuropeptide Y (36aa) containing neurons have cell bodies in arcuate nucleus  project to PV nucleus. Neuropeptide Y mRNA in hypothalamus  ↑ es during feeding; ↓ es during satiety. It exerts its effects thro’ Y5 receptors. Knocking out of this gene – animal eats less.

2. Orexins ↑se food intake by acting on 2 receptors. Orexins are synthesized in neurons located in lat. hypothalamus. Mutation in one of the orexin receptor gene – narcolepsy in dogs. Ghrelin : Endogenous ligand for GH secretagogue receptors in ant. Pituitary. Principal source of peripheral ghrelin is stomach. Central as well as peripheral administration of ghrelin  ↑food intake with common site of +ion – arcuate nucleus; part of this nucleus is outside the BBB.

3. Leptin : Protein with 167aa; product of ob gene, produced primarily in fat cells. Acts on hypothalamus to ↓food intake & ↑energy consumption. ↓ es activity of neuropeptide Y neurons. ↑ es activity of POMC secreting neurons. db gene – produces several forms of leptin receptors : Long form – found in hypothalamus; mediates central appetite & energy reg. & is plenty in arcuate nucleus. Gold thioglucose causes obesity by destroying this nucleus. To reach central site of action, leptin has to cross BBB. Short form – abundant in brain microvessels , transports leptin into brain.

4. Mech. of action : Leptin activates phosphatidyl inositol-3-hydroxykinase in hypothalamic cells. Leptin ↑ es activity of Supressor of Cytokine signalling 3 in neuropeptide Y neurons & this supresses further leptin receptor signalling  TURN OFF MECH. Leptin when infused into cerebral ventricles  bone loss. Fasting  ↓ leptin  –ion of onset of puberty, depressed thyroid function & ↑GC secretion. Leptin receptors are present in brown adipose tissue. Leptin ↑ es activity of uncoupling proteins  direct peripheral ↑se in energy expenditure.

5. Leptin operates as part of feedback loop by which size of body fat depots can operate thro’ a humoral link to regulate food intake.

6. Mech. of reg. of body weight Lipostatic hypothesis : size of body fat depot- sensed by neural/hormonal signals – relay to brain – control of appetite Gut peptide hypothesis : food in GIT – secretion of GI hormones- inhibit further food intake. Glucostatic hypothesis : Thermostatic hypothesis

7. Reg. of sexual behavior Amygdala  stria terminalis  preoptic area  tuberal region. Tuberal region maintains basal secretion of GnRH ; its connection with preoptic area – cyclical surge of gonadotropin before ovulation. Electrical +ion of preoptic area – ovulation. Destruction of neural links btn preoptic & tuberal region prevents ovulation. Ant. ventral hypothalamic nuclei is responsible for reg. of sexual behavior in females. In males - pyriform cortex.

8. Reg. of circadian rhythm Refers to rhythmic fluctuations in certain physiological parameters of the body. Suprachiasmatic nuclei entrain the rhythm in all cells except in liver. Aff . : retinohypothalamic fibres pass via optic chiasma to SCN; lat. Geniculate nuclei. Eff. : from SCN initiate neural & humoral signals controlling Rhythms in secretion of ACTH. Rhythmic secretion of growth hormone. Sleep-wake cycle. Activity patterns. Secretion of pineal hormone melatonin. Body temp. rhythm. Rhythmic gonadotropin secretion.

9. Genes in neurons are activated diurnally Protein products enter cytoplasm Modify cell function; & thus neuronal discharge Modified proteins Return to nucleus Inhibits gene activity

10. Normally rats show locomotor activity in dark & inactivity in day time. These cycles continue even when rats are put permanently in darkened lab for few days with no exposure to light. Cycles of activity & inactivity can be disrupted by bilat . Lesions in SCN.

11. Reg. of sleep Sleep zones : Diencephalic sleep zone – post. hypothalamus, intralaminar & ant. thalamic nuclei. Medullary synchronizing zone – reticular formation of medulla oblongata at the level of NTS. Basal forebrain sleep zone – preoptic area & diagonal band of Broca . Serotonin antagonist ritanserin - ↑slow wave sleep. Adenosine – sleep inducing factor. Caffeine – adenosine antagonist.

12. Stress!! The HPA axis controls a major endocrine response to stress : 1. Sensory input activates the amygdala . 2. Amygdala activates the paraventricular nucleus of the hypothalamus (PVN). 3. The PVN releases corticotropin -releasing factor (CRF) into portal blood to activate the pituitary. 4. The pituitary releases adrenocorticotropic hormone (ACTH). 5. ACTH causes glucocorticoid release from the adrenals.

13. Applied aspects Lesions of hypothalamus : tumour , encephalitis, ischemia, damage due to surgery in this area. Disturbances in hypothalamic lesions: Autonomic disturbances. Disturbances in body temp. reg. Sleep disturbances due to lesions in mammillary body & ant. Hypothalamus. Endocrine abnormalities – hypogonadism , hypothyroidism. Disturbances in sexual function. Disturbance of body water balance due to damage to SO nuclei or infundibular stalk, characterised by excessive thirst & polyuria . Emotional disturbances due to lesions in ventromed . & posterolat . Nuclei.

14. Clinical conditions of hypothalamic lesions Diabetes insipidus : due to def. of ADH – tumour / lesions of ant. Hypothalamus in which SO nuclei are damaged – excessive thirst & polyuria . Narcolepsy : sudden attacks of irresistable desire of sleep (few seconds to 20 min) during day time. Cataplexy : sudden emotional outburst of anger, fear or excitement (few min) ass. with narcolepsy.

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