1. Hypothalamus BLOCK 3 – 2011-12 Robert R. Terreberry, PhD Room 142 Ph 864.327.9827 rterreberry@carolinas.vcom.edu

2. Hypothalamic Zones Mid-sagittal

3. Hypothalamus Scheme

4. Hypothalamus Levels

5. Supraoptic Zone

6. Tuberal Zone

7. Mamillary Zone

8. Hypothalamic Afferents

9. Hypothalamic Efferents

10. Hypothalamus Connections

11. Pituitary Gland Herring body NeuralPortal

12. Hypothalamus Scheme

13. Functional Areas SUPRAOPTIC ZONE TUBERAL ZONE MAMILLARY ZONE ADH / Oxytocin Para. Responses Lower Body Temp. Sleep / Rhythms Releasing Factors Satiety Center Avoidance Reactions / Fear Symp. Responses Raise Body Temp. Waking Sympathetic Responses Feeding Center Thirst Center Anterior Posterior Preoptic Area Medial

14. Parasympathetic Areas SUPRAOPTIC ZONE TUBERAL ZONE MAMILLARY ZONE ADH / Oxytocin Para. Responses Lower Body Temp. Sleep / Rhythms Releasing Factors Satiety Center Avoidance Reactions / Fear Symp. Responses Raise Body Temp. Waking Sympathetic Responses Feeding Center Thirst Center Anterior Posterior Preoptic Area Medial

15. Sympathetic Areas SUPRAOPTIC ZONE TUBERAL ZONE MAMILLARY ZONE ADH / Oxytocin Para. Responses Lower Body Temp. Sleep / Rhythms Releasing Factors Satiety Center Avoidance Reactions / Fear Symp. Responses Raise Body Temp. Waking Sympathetic Responses Feeding Center Thirst Center Anterior Posterior Preoptic Area Medial

16. Temperature Regulation SUPRAOPTIC ZONE TUBERAL ZONE MAMILLARY ZONE ADH / Oxytocin Para. Responses Lower Body Temp. Sleep / Rhythms Releasing Factors Satiety Center Avoidance Reactions / Fear Symp. Responses Raise Body Temp. Waking Sympathetic Responses Feeding Center Thirst Center Anterior Posterior Preoptic Area Medial

17. Circadian Fluctuation in Core Body Temperature Temperature Regulation Body Temperature (°C)

18.  Temperature affects Ant. Hypothalamus / Preoptic Area Temperature Regulation Promote Heat Loss Sweating Vasodilation Behavioral  ’s Prevent Heat Production  muscle tone / activity  thyroid hormone / epinephrine  appetite (calories)

19.  Temperature affects Post. Hypothalamus Temperature Regulation Promote Heat Production Shivering,  muscle tone  thyroid hormone / epinephrine Prevent Heat Loss Vasoconstriction Behavioral  ’s

20. Lesion of Anterior Hypothalamus Temperature Regulation Inability to lower body temperature Hyperthermia in a hot environment 41˚C (106˚F) – convulsions 43˚C (109˚F) – death Inability to increase body temperature Hypothermia in a cold environment Confusion followed by loss of thermoregulation at 28˚C (82˚F) Lesion of Posterior Hypothalamus

21. Interleukin-1 is endogenous pyrogen Released from macrophages Acts on neurons and glia in medial preoptic area – “pyrogenic zone” Glial cells produce cytokines and PGE 2 PGE 2  cold-sensitive neurons PGE 2  warm-sensitive neurons PGE 2 will increase temperature set-point and thus body temperature will rise - fever Fever

22. Febrile Conditions Body Temperature (°F)

23. Feeding Regulation SUPRAOPTIC ZONE TUBERAL ZONE MAMILLARY ZONE ADH / Oxytocin Para. Responses Lower Body Temp. Sleep / Rhythms Releasing Factors Satiety Center Avoidance Reactions / Fear Symp. Responses Raise Body Temp. Waking Sympathetic Responses Feeding Center Thirst Center Anterior Posterior Preoptic Area Medial

24. Feeding Regulation Feeding Center Lateral hypothalamic nucleus Stimulated by low glucose levels Initiates feeding Amphetamines inhibit food intake by enhancing Norepi and DA levels in lateral hypothalamic nucleus Ventromedial nucleus Stimulated by high glucose levels or CCK Inhibits food intake Satiety Center

25. Feeding Regulation Leptin Protein hormone released by fat cells Circulating levels directly proportional to amount of adipose tissue in body Acts on receptors in lateral hypothalamus Inhibits affects of neuropeptide Y and anandamine – both feeding stimulants Inhibits feeding Genetically altered mice with no leptin or leptin receptors are obese

26. Feeding Regulation Ghrelin Hormone that stimulates appetite Produced in stomach and upper small intestine in response to significant weight loss May explain why it is difficult to maintain weight loss after dieting Not produced in patients that have undergone gastric bypass surgery

27. Lesion of feeding center Feeding Regulation - Lesions Results in loss of desire to eat Leads to aphagia and ultimately death Results in compulsive overeating Leads to hyperphagia and obesity Lesion of satiety center

28. Water (Fluid) Regulation SUPRAOPTIC ZONE TUBERAL ZONE MAMILLARY ZONE ADH / Oxytocin Para. Responses Lower Body Temp. Sleep / Rhythms Releasing Factors Satiety Center Avoidance Reactions / Fear Symp. Responses Raise Body Temp. Waking Sympathetic Responses Feeding Center Thirst Center Anterior Posterior Preoptic Area Medial

29. Fluid Regulation Thirst Center In anterior and lateral hypothalamus Closely tied to supraoptic/ADH system controlling fluid homeostasis Stimulation results in fluid consumption - polydipsia Ventromedial nucleus Tied to food intake Food and fluid intake not mutually exclusive Satiety Center

30. Lesion of lateral hypothalamus Fluid Regulation - Lesions Loss of thirst center Results in very little fluid intake - adipsia Results in compulsive overeating/drinking Leads to hyperphagia and polydipsia Lesion of satiety center

31. Sexual Behaviors SUPRAOPTIC ZONE TUBERAL ZONE MAMILLARY ZONE ADH / Oxytocin Para. Responses Lower Body Temp. Sleep / Rhythms Releasing Factors Satiety Center Avoidance Reactions / Fear Symp. Responses Raise Body Temp. Waking Sympathetic Responses Feeding Center Thirst Center Anterior Posterior Preoptic Area Medial

32. Sexual Behaviors Preoptic area regulates release of gonadotrophic hormones Cyclical in females Topical with fluctuations in males Preoptic area important in male behaviors - mounting Ventromedial nucleus important in female behaviors - lordosis

33. Preoptic area is different in males and females Sexually dimorphic nucleus Larger in male rats vs female rats Sexual Orientation

34. Human studies Simon LeVay INAH-3 smaller in homosexual males, size of heterosexual females Sexual Orientation

35. Human studies Laura Allen and Roger Gorski Area of anterior commissure is normally larger in women than men Anterior commissure 34% larger in homosexual males than in heterosexual males; 18% larger than those in heterosexual females Dick Swaab Suprachiasmatic nucleus larger (twice the number of cells) in homosexual males than in heterosexual males Sexual Orientation

36. Human studies Savic et al. PET scans of heterosexual subjects smelling putative human pheromones AND (in male sweat), EST (in pregnant female urine) HeW (AND) = preoptic area and DM hypo. HeM (EST) = PVN and DM hypothalamus HeW (EST) and HeM (AND) = areas that process common odors, no hypothalamus Sexual Orientation

37. Human studies Savic et al. PET scans of homosexual male and heterosexual female subjects smelling putative human pheromones HoM (AND) = PVN and DM hypothalamus HeW (AND) = PVN and DM hypothalamus Sexual Orientation

38. Human studies Lindstrom and Savic PET scans of lesbian subjects smelling putative human pheromones HoW (AND) = olfactory networks, not hypo. HoW (EST) = partly shared responses with HeM - anterior hypothalamus Sexual Orientation

40. Fear and Pleasure SUPRAOPTIC ZONE TUBERAL ZONE MAMILLARY ZONE ADH / Oxytocin Para. Responses Lower Body Temp. Sleep / Rhythms Releasing Factors Satiety Center Avoidance Reactions / Fear Symp. Responses Raise Body Temp. Waking Sympathetic Responses Feeding Center Thirst Center Anterior Posterior Preoptic Area Medial

41. Fear and Pleasure Flight response Stimulation of lateral anterior hypothalamus Sympathetic response Ventromedial nucleus stimulation Defensive response - fear Avoidance reaction Preoptic area stimulation Pleasure

42. Circadian Rhythms SUPRAOPTIC ZONE TUBERAL ZONE MAMILLARY ZONE ADH / Oxytocin Para. Responses Lower Body Temp. Sleep / Rhythms Releasing Factors Satiety Center Avoidance Reactions / Fear Symp. Responses Raise Body Temp. Waking Sympathetic Responses Feeding Center Thirst Center Anterior Posterior Preoptic Area Medial

43. Circadian Rhythms Suprachiasmatic nucleus is considered to be the biological clock Endogenous rhythm with 24 hour periodicity Rhythm influenced by light Retina projects directly to SCN

44. Sleep and Wakefulness SUPRAOPTIC ZONE TUBERAL ZONE MAMILLARY ZONE ADH / Oxytocin Para. Responses Lower Body Temp. Sleep / Rhythms Releasing Factors Satiety Center Avoidance Reactions / Fear Symp. Responses Raise Body Temp. Waking Sympathetic Responses Feeding Center Thirst Center Anterior Posterior Preoptic Area Medial

45. Sleep and Wakefulness In anterior hypothalamus / preoptic area Production of PGD 2 promotes sleep Lesions result in insomnia In posterior hypothalamus Production of PGE 2 promotes waking Lesions result in hypersomnolence

46. Questions??