1. Hypothalamus Chapter 6
Center that integrates autonomic, endocrine and behavioral responses
Regulates the internal environment (homeotasis)
Makes survival and propagation more likely
Combination of neural and endocrine inputs and outputs
Plays a major role in functions as diverse as feeding, drinking, temperature regulation, sexual responses and determining “How you feel.”

6. Hypothalamus and Homeostasis
Close tolerances necessary for life
Small percentage change in body temperature, electrolytes, and blood pH can cause death
Homeostasis and the internal milieu
Interface between external and internal environment
Endocrine system
Autonomic nervous system

7. Hypothalamic Role in Emotion
Visceral Afferents
Hypothalamic Nuclei
Hormonal Output
Nucleus of the Solitary Tract
Target Organs
Autonomic Output
Autonomic Preganglionic Nuclei
Brain Stem Nuclei

8. Hypothalamus Pituitary Releasing Factors Autonomic Nervous System
Sympathetic
Adenohypophysis (Anterior Pituitary)
Neurohypophysis (Posterior Pituitary)
Parasympathetic

10. “I feel fear!”

11. Hypothalamus Amygdala Anterior Nucleus Brainstem Cortex, septum
stria terminalis
Amygdala
mtt
Anterior Nucleus
dorsal long. fasciculus
Brainstem
medial forebrain bundle
Cortex, septum
Hypothalamus
ventral route
medial forebrain bundle
Amygdala
Brainstem spinal cord
parvo
magno (SO, PV)
ant.
post.
Pituitary

13. Hypothalamus Amygdala Anterior Nucleus Brainstem Cortex, septum
stria terminalis
Amygdala
mtt
Anterior Nucleus
dorsal long. fasciculus
Brainstem
medial forebrain bundle
Cortex, septum
Hypothalamus
ventral route
medial forebrain bundle
Amygdala
Brainstem spinal cord
parvo
magno (SO, PV)
ant.
post.
Pituitary

14. The hypothalamus not only influences how you feel, it influences how you interpret the consequences of those feelings.

16. Hippocampal formation
stria terminalis
Amygdala
humoral, temperature
fornix
Physical inputs
Hippocampal formation
dorsal long. fasciculus
Brainstem
medial forebrain bundle
Cortex, septum
Hypothalamus
optic tract
medial forebrain bundle
Retina
Brainstem spinal cord
ventral route
Amygdala

17. Thermo-regulation (body temperature)
Involves autonomic nervous, endocrine, and skeletomotor systems
Body temperature detectors
Peripheral: skin, spinal cord, viscera
Central: anterior hypothalamus
Body temperature effectors
Heat retention or generation: posterior hypothalamus
Heat dissipation: anterior hypothalamus

18. Thermo-regulation (body temperature)
Heat dissipating mechanisms
Dilation of blood vessels in the skin
Inhibition of shivering
Heat conserving mechanisms
Vasoconstriction of blood vessels in the skin
Shivering
Increased secretion of thyroxin

20. Temperature control center
Temperature control center. In the mammalian brain, a series of neural pathways (red) control the body’s autonomic responses that regulate heat conservation and production, respectively.
Cells in the paraventricular and dorsomedial hypothalamic nuclei, and in the raphe (5HT), signal to sympathetic preganglionic neurons in the spinal cord to control thermogenesis.
These pathways are in turn regulated by an inhibitory input (blue) from the medial preoptic hypothalamus that is responsive to preoptic temperature.

21. Thermogenesis is subserved by neural inputs to brown adipose tissue, at least in small mammals, where β3 adrenergic receptors mediate production of uncoupling protein 1 (UCP-1). UCP-1 allows mitochondria in brown adipose tissue to convert adenosine 5'-triphosphate (ATP) to heat, rather than to energy for performing work. Thus, small mammals that lack sufficient mass for heat retention carry portable heaters in the form of brown adipose tissue that allow them to avoid hypothermia.

22. Low body temperature does prolong life span in poikilothermic fish (in which body temperature fluctuates with that of the external environment) Homeotherms with a restricted caloric intake develop a low body temperature and also have a prolonged life span.
one might wonder whether 37°C is indeed the optimal body temperature for humans, and why evolution has not selected for a lower body temperature and longer life span. However, there would be little evolutionary pressure to extend the number of years of life after reproduction is finished

23. Methods of thermo-regulation by the body
Response to Cold
Response to Heat
Methods of thermo-regulation by the body

25. Disorders of Thermo-regulation
Lesions of heat conserving mechanisms
Lesion of posterior hypothalamus
Causes hypothermia
Lesions of heat dissipating mechanisms
Lesion of anterior hypothalamus
Causes hyperthermia
Disconnection syndrome
Thermo-regulator mechanisms separated from effectors
Cannot control skin vasodilatation
Cannot shiver
Causes piokoliothermia

26. Hyperpyrexia Malignant Hyperthermia Response to general anesthesia
Associated with neuroleptic medications
Interferes with dopamine function in the hypothalamus
Interference with peripheral heat dissipating mechanism
Anti-cholinergic medications interfere with sweating and heat dissipation

27. Hypothalamus
Center that integrates autonomic, endocrine and behavioral responses
Regulates the internal environment (homeotasis)
Makes survival and propagation more likely
Combination of neural and endocrine inputs and outputs
Plays a major role in functions as diverse as feeding, drinking, temperature regulation, sexual responses

28. (CSF 1%)

29. Thirst Function of serum osmolality and blood volume
Osmotic receptors in the hypothalamus
Volume receptors in the right atrium of the heart and great veins
Vasopressin release from hypothalamus
Increases water reabsorption from the kidney
Inhibited by ethanol
Neurogenic diabetes insipidus

30. OVLT

31. Two Kinds of Thirst

32. Drinking Behavior Shorter stay = more drinks/hr
Drinking alone = more drinks/hr
Rhythm that equals the heart rate = more drinking
Lyrics: sad songs = more drinking
More men than women = more drinking
Live band = more drinking
Action photography = more drinking

33. Circadian Rhythm Oscillations during the course of the day
Corticosteriods
Feeding and drinking behavior
Growth hormone secretion
Lesions of the suprachiasmatic nuclei of the hypothalamus disrupts these oscillations

34. Suprachiasmatic Nucleus

36. Biological Clocks May Exist in All Cells of the Body

37. Effects on Cardiovascular Function
Main centers for controlling heart rate and contractility are in the medulla
Lesions of the hypothalamus can cause abnormalities in cardiac conduction
Subarachnoid hemorrhage can produce EKG abnormalities due to direct irritation of the hypothalamus

38. Control of Feeding

39. Feeding Complex interaction of many systems
Regulation of energy metabolism by the Ventromedial and Lateral nuclei of the hypothalamus
Physical Lesions produce hyperphagia and obesity or reduced attention to food.
Amygdala may also be involved indirectly
Lesions produce hyperphagia-like symptoms
Ventromedial hypothalamic lesions also cause increased insulin secretion Obesity.

42. Feedback Mechanisms Controlling Feeding
Notion of "Set Point"
Feedback from gut hormones
e.g. Cholecystokinin
Released from small intestine in response to feeding
Inhibits or suppresses feeding
Slow onset

44. The Yin and Yang personalities of ghrelin and obestatin.
Both hormones derive from the same precursor protein and are predominantly secreted by the stomach and released into the blood. Each acts on a different receptor (GPR39 and GHS-R, as shown) and has an opposite effect on food intake, body weight, and gastrointestinal motility. K. SUTLIFF/SCIENCE, 2005

46. Dietary polyunsaturated fatty acids are incorporated into membrane phospholipids, which can subsequently be metabolized into the two major endocannabinoids, 2-AG and anandamide, by membrane-associated enzymes.
Degradative enzymes for endocannabinoids are localized to internal membranes. Leptin signaling can influence 2-AG biosynthesis in the hypothalamus and anandamide hydrolysis

47. Reactions to pain were suppressed during chocolate eating
Ingestion analgesia functions to defend eating from ending. Humans become hyperphagic when palatable food is readily available suggesting that tasty food within easy reach is destined for defended consumption in humans as well as other animals. Humans eat more when more food is available even when the food is stale or even when they are made cognizant of this tendency . The biological drive to consume palatable foods to completion outweighs opposing cognitive and motivational factors and is likely a major factor in the recent dramatic increase in obesity in modern human societies.
Copyright ©2009 Society for Neuroscience
Foo, H. et al. J. Neurosci. 2009;29:

49. Relation between body size and metabolism
Basal Metabolic Rate
Body Weight

50. Probability of dying from any cause
Data for 1,000,000 people

51. Effect of caloric intake on:
Body weight
Percent survival
Life-span

52. The potential synergy between diet & exercise could involve common cellular pathways
important for neurogenesis, cell survival, synaptic plasticity and vascular function.
Optimal maintenance of brain health might depend on exercise and intake of natural products.
Van Praag, TINS, 2009

54. OXYGEN: A Pro-Aging Molecule
The risk is simply being alive, e.g. breathing, eating, exercising…
2% of oxygen used in energy metabolism forms oxygen free radicals that are toxic and may damage DNA.
The complement of anti-oxidant systems your species possesses is directly related to how long your species lives.

55. Effect of Caloric Restriction on Mice Fewer cancerous tumors among those on restricted diets45 15 11 9
2.1 1
Tumors, including hepatoma (cancer of the liver) and lymphoma (cancer of the lymph system) were fewer in 2-year -old mice on the caloric restriction diet compared to mice on the regular diet.
Source: R.T. Bronson and R.D. Lipman, Growth, Development and Aging, 1991.

56. Degenerative Diseases Control Rats vs. Restricted Rats95 80 75 55 35 25 19 18
Diaease Type
The incidence of degenerative disease of the kidney, muscle, heart, and blood vessels, in 2-year-old rats is higher on regular than on CR diets
Source: B.N. Berg, in Hypothalamus, Pituitary and Aging, 1976.

58. Obesity: Why do we eat so much?
Evolutionary: the fittest individuals preferred a high calorie diet, ate to capacity, stored excess calories as fat and used those stores as efficiently as possible.
Cultural: 3 meals/day regardless of whether you’re hungry.
Social: high caloric food during gatherings with friends.

59. Obesity: Why do we eat so much?
We live in an environment in which an endless variety of foods of the highest positive-incentive value are readily and continuously available.

60. Obesity
Average quality-of-life rating assigned to U.S. children with cancer: 69
Average quality-of-life rating assigned to obese children: 67

61. Obesity Treatment: Less eating or more exercise?
Simple exercise contributes little to weight loss.
Physical activity consumes only a small portion of total energy.
80% of energy is used to maintain resting physiological processes and to digest food.

64. Liposuction?