BIO 132BIO 132NeurophysiologyNeurophysiology

Lecture 35Lecture 35MotivationMotivation

Lecture Goals:Lecture Goals: Understanding the underlying mechanisms Understanding the underlying mechanisms

affecting rudimentary motivations (hunger, affecting rudimentary motivations (hunger, thirst, warmth, etc).thirst, warmth, etc).

Appreciating the common elements behind Appreciating the common elements behind the feedback loops controlling hunger, the feedback loops controlling hunger, thirst, and temperature regulation.thirst, and temperature regulation.

Motivation – the driving force behind behaviorMotivation – 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 GoalSit in classGet food

UrinateListen to music

Sit in class

Motivations

Behavior

Hunger: the motivation to eatHunger: the motivation to eat Hunger is affected by more than one Hunger is affected by more than one

homeostatic feedback loop.homeostatic feedback loop. Maintenance of blood glucose levels (short-Maintenance of blood glucose levels (short-

term feeding behavior)term feeding behavior) Maintenance of fat stores (long-term feeding Maintenance of fat stores (long-term feeding

behavior)behavior) Hunger can also be affected by things other Hunger can also be affected by things other

than homeostatic feedback loops such as mood than homeostatic feedback loops such as mood (bored, sad, happy, anxious, etc).(bored, sad, happy, anxious, etc).

Hunger

Goal of long-term feeding behavior: Goal of long-term feeding behavior: Maintain long-term energy stores (fat).Maintain long-term energy stores (fat).

Fat has twice the energy (per weight) Fat has twice the energy (per weight) as glucose and doesn’t require excess as glucose and doesn’t require excess water storage like glucose (fat isn’t water storage like glucose (fat isn’t osmotically active).osmotically active).

The body has a set-point for the The body has a set-point for the amount of fat it would like stored on amount of fat it would like stored on the body.the body.

Long-term Feeding Behavior

Experimentally, rats were given food to eat Experimentally, rats were given food to eat whenever they wanted (whenever they wanted (ad libitumad libitum), but at two ), but at two time periods of the experiment were deprived of time periods of the experiment were deprived of food and forced fed.food and forced fed.

Maintenance of Fat Stores

Time (days)

Bod

y w

eigh

t (g)

fasted force-fed

set-point

Caloric intake = caloric expenditure Normal weightCaloric intake = caloric expenditure Normal weight

Caloric intake > caloric expenditure Gain weightCaloric intake > caloric expenditure Gain weight

Caloric intake < caloric expenditure Lose weightCaloric intake < caloric expenditure Lose weight

Energy Balance

First proposed in 1953, the First proposed in 1953, the lipostatic lipostatic hypothesishypothesis states that the brain states that the brain monitors fat levels and maintains monitors fat levels and maintains them at some fixed set-point amount.them at some fixed set-point amount.

The lipostatic hypothesis requires that The lipostatic hypothesis requires that the fat communicate with the brain in the fat communicate with the brain in some way.some way. First suspected was some blood-borne First suspected was some blood-borne

chemincal (a hormone).chemincal (a hormone).

Lipostatic Hypothesis

Evidence of a hormone from the fat Evidence of a hormone from the fat (1960s):(1960s): Parabiosis (the fusing of two animals so that Parabiosis (the fusing of two animals so that

they share the same blood) of a genetically they share the same blood) of a genetically obese mouse to a normal mouse caused the obese mouse to a normal mouse caused the obese mouse to become thin (normal weight).obese mouse to become thin (normal weight).

Hormone from Fat

Obese Normal Surgically fused(share blood)

It was apparent that the blood carried It was apparent that the blood carried some signal to the brain from the fat that some signal to the brain from the fat that allowed the brain to monitor the levels of allowed the brain to monitor the levels of fat.fat.

The hormone went undiscovered until The hormone went undiscovered until 1994.1994.

The gene that made genetically obese The gene that made genetically obese mice (ob/ob) was finally isolated and its mice (ob/ob) was finally isolated and its product synethesized.product synethesized. The product of the gene was named The product of the gene was named leptinleptin

Hormone from Fat

Once isolated an synthesized, leptin Once isolated an synthesized, leptin could be injected into obese mice could be injected into obese mice (ob/ob) that cannone make leptin (ob/ob) that cannone make leptin themselves, and the mice would themselves, and the mice would become thin (normal weight).become thin (normal weight).

Hormone from Fat - Leptin

Obese(ob/ob)

Normal

leptin

It was known since the 1940s that destruction of the It was known since the 1940s that destruction of the hypothalamus led to abnormal food intake.hypothalamus led to abnormal food intake.

Leptin was theorized to have its effect on the Leptin was theorized to have its effect on the hypothalamus.hypothalamus.

It is now known that leptin binds to It is now known that leptin binds to ααMSH and CART MSH and CART receptors in the arcuate nucleus of the hypthalamus.receptors in the arcuate nucleus of the hypthalamus. ααMSH stands for alpha-melanocyte-stimulating hormone.MSH 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.* You do not need to memorize these names, just the abbreviations.

How Does Leptin Work?

Once leptin binds to receptors in the arcuate Once leptin binds to receptors in the arcuate nucleus, activated neurons project to the nucleus, activated neurons project to the periventricular and the lateral zones.periventricular and the lateral zones.

The periventricular zone activates both the The periventricular zone activates both the sympathetic NS and neurons projecting to the sympathetic NS and neurons projecting to the pituitary gland.pituitary gland. Activated SNS causes in increase in metabolism Activated SNS causes in increase in metabolism

(burning calories).(burning calories). Hypothalamic neurons projecting to the pituitary release Hypothalamic neurons projecting to the pituitary release

thyroid releasing hormone (TRH) which causes the thyroid releasing hormone (TRH) which causes the release of thyroid stimulating hormone (TSH) from release of thyroid stimulating hormone (TSH) from secretory cells in the anterior pituitary, causing the secretory cells in the anterior pituitary, causing the release of thyroid hormone from the thyroid gland, release of thyroid hormone from the thyroid gland, increasing metabolism.increasing metabolism.

Effects of Leptin on the Arcuate Nucleus

Other hypothalamic neurons projecting to the Other hypothalamic neurons projecting to the pituitary release corticotropin releasing hormone pituitary release corticotropin releasing hormone (CRH) which causes the release of (CRH) which causes the release of adrenocorticotropic hormone (ACTH) from adrenocorticotropic hormone (ACTH) from secretory cells of the pituitary, causing the release secretory cells of the pituitary, causing the release of cortisol from the adrenal gland which increases of cortisol from the adrenal gland which increases metabolism. metabolism.

The lateral zone activates neurons that The lateral zone activates neurons that decrease the motivation to eat by decreasing decrease the motivation to eat by decreasing hunger and increasing the feeling of satiety. hunger and increasing the feeling of satiety. This decreases caloric intake.This decreases caloric intake.

Effects of Leptin on the Arcuate Nucleus

Effects of Leptin

vent

rica

l

Arcuate nucleus

Lateral zonePeriventricularzone

nutrients

Fat

leptin

αMSHCART

PituitaryFeeding behavior

TRH

TSH

thyroid hormone

CRH

ACTH

cortisol

Metabolic rate

SatietyHunger

Caloric intake

SNS

inhibit