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Hypothalamus and Homeostasis PSY391S March 13, 2006 John Yeomans Hypothalamus Functions • “We are the accumulation of mechanisms that allowed our ancestors to survive and reproduce their genes” (Sagan) • Hypothalamus is an accumulation of tiny nuclei for survival and reproduction. • Hormones and neural signals to and from viscera. • Motivated behaviors to respond to internal challenges. • Homeostasis maintains internal environment. Reproduction changes environment. Hormonal and Neural Signals • Hypothalamus controls pituitary hormones acting on many organs. • Hypothalamus receives hormonal inputs by way of circumventricular organs. • Hypothalamus coordinates neural and hormonal signals for visceral control (Autonomic NS) and motivated behaviors. • Hypothalamus receives neural inputs from descending limbic/olfactory systems and ascending taste/visceral systems. Posterior Pituitary Hormones to Brain • Blood-brain barrier (glia surrounding brain vessels) prevents entry of large molecules in most brain regions. • Leaky capillaries in 6 tiny nuclei near ventricles allow entry of hormones. • Circumventricular organs have receptors for many circulating hormones (e.g. leptin, angiotensin II, gonadal hormones). Circumventricular Organs Subcommissural organ Arcuate N. Posterior Pituitary Endotherms • Birds and mammals control body temperature near 37ºC. • Advantages: Constant physiology, better brain function, bigger brains, and adaptation to extreme environments. • Costs: More insulation needed (fat, feathers, fur), more energy needed, more internal controls. Temperature Control Systems Temperature Hypothalamus maintains temperature best. Fluid Regulation • Body made up of ~65% H2O, for cell chemistry, and for movement of nutrients and cells (e.g. blood and lymph). • Salt concentration maintained at 0.9%. • Intracellular and extracellular compartments separated by semipermeable membranes that control ions and other chemicals. Water and Salt Regulation Thirst Water Loss: respiration, sweating, urination, defecation, bleeding. Salt loss. Water Intake: drinking, feeding, Salt content. Renin-Angiotensin 14 AA Blood Kidney 10 AA 8 AA 7AA Adrenals Neural control of blood pressure Behavioral control of water and salt. Hormonal control of blood pressure and tonicity Vasoconstriction & H20 reuptake in kidney Energy Sources • • • • • • • Carbohydrates-->Glucose Proteins-->Amino acids Fats-->Fatty acids These are stored in the body: Fat cells (long-term) 80-90% of total Muscle and liver glycogen (starch) Blood glucose, fatty acids and amino acids. (short-term) • Ketones used if blood glucose low. Insulin and Glucagon • Pancreas hormones made by beta and alpha cells of Islets of Langerhans. • High blood glucose activates insulin; low blood glucose activates glucagon. • Insulin activates transport of glucose into body cells (not brain). • Glucagon converts glycogen into glucose. • This keeps blood glucose levels stable. Brain Energy • Uses glucose and O2 only (Ketones in starvation). • Does not need insulin so always gets glucose. • Brain uses over 20% of glucose and O2. • Fainting helps brain get these when blood pressure drops. Feeding and Obesity John Yeomans PSY391S March 15, 2006 Hypothalamus and Feeding Brain Lesions and Stimulation • LH and PVN lesions--> less eating; VMH and arcuate lesions--> more eating. • LH stimulation-->eating; VMH-->aversion. • PVN-->NPY and NE increases feeding; 5HT decreases feeding. • Therefore, LH and PVN for feeding, VMH for satiety. ob/ob or db/db mice - (-/-) (+/+) Leptin and Obesity • ob/ob and db/db mice are obese, and eat fats as if starving. • ob/ob mice have mutation in leptin gene. • Leptin is peptide produced in fat cells in proportion to size. • db/db mice have mutation in leptin receptor gene. • Leptin receptors in arcuate n. and LH. Short-Term Feeding Signals • Taste and smell (accept or reject). • Stomach--ghrelin, distension, vomiting (area postrema). • Intestines, pancreas, gall bladder-hormones (CCK, insulin, PYY3-36), • Liver-->vagus to N. Solitary Tract, area postrema-->parasympathetic and sympathetic. • Hypothalamus--hormone receptors, neural systems, motivated behaviors. Human Obesity • Starvation-->hunger, depression and poor health. Exercise healthier, but harder. • Surgery--liposuction, stomach resection. Still hungry. • Leptin insensitivity. Leptin is high, but hypothalamus doesn't respond. • Serotonin (fenfluramine, SSRIs) works, but has side effects.