1. BIO 132 Neurophysiology Lecture 35 Motivation

2. Lecture Goals: Understanding the underlying mechanisms affecting rudimentary motivations (hunger, thirst, warmth, etc). Understanding the underlying mechanisms affecting rudimentary motivations (hunger, thirst, warmth, etc). Appreciating the common elements behind the feedback loops controlling hunger, thirst, and temperature regulation. Appreciating the common elements behind the feedback loops controlling hunger, thirst, and temperature regulation.

3. Motivation – the driving force behind behavior Motivation – the driving force behind behavior The brain area(s) responsible for keeping track and deciding on what the current behavior should be is still unknown. The brain area(s) responsible for keeping track and deciding on what the current behavior should be is still unknown. Many motivations arise from internal homeostatic feedback loops. Many motivations arise from internal homeostatic feedback loops. Motivation Current Goal Sit in class Get food Urinate Listen to music Sit in class Motivations Behavior

4. Hunger: the motivation to eat Hunger: the motivation to eat Hunger is affected by more than one homeostatic feedback loop. Hunger is affected by more than one homeostatic feedback loop. Maintenance of blood glucose levels (short-term feeding behavior) Maintenance of blood glucose levels (short-term feeding behavior) Maintenance of fat stores (long-term feeding behavior) Maintenance of fat stores (long-term feeding behavior) Hunger can also be affected by things other than homeostatic feedback loops such as mood (bored, sad, happy, anxious, etc). Hunger can also be affected by things other than homeostatic feedback loops such as mood (bored, sad, happy, anxious, etc). Hunger

5. Goal of long-term feeding behavior: Maintain long-term energy stores (fat). Goal of long-term feeding behavior: Maintain long-term energy stores (fat). Fat has twice the energy (per weight) as glucose and doesn’t require excess water storage like glucose (fat isn’t osmotically active). Fat has twice the energy (per weight) as glucose and doesn’t require excess water storage like glucose (fat isn’t osmotically active). The body has a set-point for the amount of fat it would like stored on the body. The body has a set-point for the amount of fat it would like stored on the body. Long-term Feeding Behavior

6. Experimentally, rats were given food to eat whenever they wanted (ad libitum), but at two time periods of the experiment were deprived of food and forced fed. Experimentally, rats were given food to eat whenever they wanted (ad libitum), but at two time periods of the experiment were deprived of food and forced fed. Maintenance of Fat Stores Time (days) Body weight (g) fasted force-fed set-point

7. Caloric intake = caloric expenditure Normal weight Caloric intake = caloric expenditure Normal weight Caloric intake > caloric expenditure Gain weight Caloric intake > caloric expenditure Gain weight Caloric intake < caloric expenditure Lose weight Caloric intake < caloric expenditure Lose weight Energy Balance

8. First proposed in 1953, the lipostatic hypothesis states that the brain monitors fat levels and maintains them at some fixed set- point amount. First proposed in 1953, the lipostatic hypothesis states that the brain monitors fat levels and maintains them at some fixed set- point amount. The lipostatic hypothesis requires that the fat communicate with the brain in some way. The lipostatic hypothesis requires that the fat communicate with the brain in some way. First suspected was some blood-borne chemincal (a hormone). First suspected was some blood-borne chemincal (a hormone). Lipostatic Hypothesis

9. Evidence of a hormone from the fat (1960s): Evidence of a hormone from the fat (1960s): Parabiosis (the fusing of two animals so that they share the same blood) of a genetically obese mouse to a normal mouse caused the obese mouse to become thin (normal weight). Parabiosis (the fusing of two animals so that they share the same blood) of a genetically obese mouse to a normal mouse caused the obese mouse to become thin (normal weight). Hormone from Fat ObeseNormalSurgically fused (share blood)

10. It was apparent that the blood carried some signal to the brain from the fat that allowed the brain to monitor the levels of fat. It was apparent that the blood carried some signal to the brain from the fat that allowed the brain to monitor the levels of fat. The hormone went undiscovered until 1994. The hormone went undiscovered until 1994. The gene that made genetically obese mice (ob/ob) was finally isolated and its product synethesized. The gene that made genetically obese mice (ob/ob) was finally isolated and its product synethesized. The product of the gene was named leptin The product of the gene was named leptin Hormone from Fat

11. Once isolated an synthesized, leptin could be injected into obese mice (ob/ob) that cannone make leptin themselves, and the mice would become thin (normal weight). Once isolated an synthesized, leptin could be injected into obese mice (ob/ob) that cannone make leptin themselves, and the mice would become thin (normal weight). Hormone from Fat - Leptin Obese (ob/ob) Normal leptin

12. It was known since the 1940s that destruction of the hypothalamus led to abnormal food intake. It was known since the 1940s that destruction of the hypothalamus led to abnormal food intake. Leptin was theorized to have its effect on the hypothalamus. Leptin was theorized to have its effect on the hypothalamus. It is now known that leptin binds to αMSH and CART receptors in the arcuate nucleus of the hypthalamus. It is now known that leptin binds to αMSH and CART receptors in the arcuate nucleus of the hypthalamus. αMSH stands for alpha-melanocyte-stimulating hormone. αMSH stands for alpha-melanocyte-stimulating hormone. CART stands for cocaine-and amphetamine-regulated transcript. CART stands for cocaine-and amphetamine-regulated transcript. * You do not need to memorize these names, just the abbreviations. How Does Leptin Work?

13. Once leptin binds to receptors in the arcuate nucleus, activated neurons project to the periventricular and the lateral zones. Once leptin binds to receptors in the arcuate nucleus, activated neurons project to the periventricular and the lateral zones. The periventricular zone activates both the sympathetic NS and neurons projecting to the pituitary gland. The periventricular zone activates both the sympathetic NS and neurons projecting to the pituitary gland. Activated SNS causes in increase in metabolism (burning calories). Activated SNS causes in increase in metabolism (burning calories). Hypothalamic neurons projecting to the pituitary release thyroid releasing hormone (TRH) which causes the release of thyroid stimulating hormone (TSH) from secretory cells in the anterior pituitary, causing the release of thyroid hormone from the thyroid gland, increasing metabolism. Hypothalamic neurons projecting to the pituitary release thyroid releasing hormone (TRH) which causes the release of thyroid stimulating hormone (TSH) from secretory cells in the anterior pituitary, causing the release of thyroid hormone from the thyroid gland, increasing metabolism. Effects of Leptin on the Arcuate Nucleus

14. Other hypothalamic neurons projecting to the pituitary release corticotropin releasing hormone (CRH) which causes the release of adrenocorticotropic hormone (ACTH) from secretory cells of the pituitary, causing the release of cortisol from the adrenal gland which increases metabolism. Other hypothalamic neurons projecting to the pituitary release corticotropin releasing hormone (CRH) which causes the release of adrenocorticotropic hormone (ACTH) from secretory cells of the pituitary, causing the release of cortisol from the adrenal gland which increases metabolism. The lateral zone activates neurons that decrease the motivation to eat by decreasing hunger and increasing the feeling of satiety. This decreases caloric intake. The lateral zone activates neurons that decrease the motivation to eat by decreasing hunger and increasing the feeling of satiety. This decreases caloric intake. Effects of Leptin on the Arcuate Nucleus

15. Effects of Leptin ventrical Arcuate nucleus Lateral zone Periventricular zone nutrients Fat leptin αMSH CART Pituitary Feeding behavior TRH TSH thyroid hormone CRH ACTH cortisol Metabolic rate Satiety Hunger Caloric intake SNS inhibit