Introduction To Behavioral Neuroscience - PSYC 211 Lecture 13 - Hunger & Thirst PDF

Introduction to Behavioral Neuroscience PSYC 211 Lecture 13 of 24 – Hunger & Thirst Chapter 9 in the textbook Professor Jonathan Britt Questions? Concerns? Please write to [email protected]  HOMEOSTASIS Cells require...

Introduction to Behavioral Neuroscience PSYC 211 Lecture 13 of 24 – Hunger & Thirst Chapter 9 in the textbook Professor Jonathan Britt Questions? Concerns? Please write to [email protected]  HOMEOSTASIS Cells require a viable temperature and food and water for survival. The temperature cannot be too hot or cold. Food and water availability must be above some threshold. Homeostasis refers to the process of actively maintaining internal conditions, particularly with respect to food and water availability and body temperature. Animals live in diverse environments because they can maintain homeostasis.  UNCONSCIOUS TEMPERATURE REGULATION When the temperature of warm-blooded (endotherm) animals deviates from a set point (~37 ˚C), the body launches corrective mechanisms. When the body is too cold…  basal metabolic rate increases; calories are burned to generate heat  the body shivers, a way of burning calories to generate heat  peripheral blood vessels constrict, moving blood to the interior of the body so less heat is lost through the skin When the body is too hot..  animals sweat or pant like a dog (breath heavily); water evaporation has a cooling effect  peripheral blood vessels expand; blood moves closer to the skin so body heat can dissipate into the surrounding air Cold-blooded (ectotherm) animals are not very good at maintaining their body temperature, so their ability to move and function is highly dependent on the ambient temperature.  CONSCIOUS TEMPERATURE REGULATION When our body temperature becomes uncomfortable, we consciously experience a need state. Need states are motivating. They drive us, push us to correct the specific problem. When a need becomes satisfied, we typically experience relief or pleasure. The anticipation of pleasure can motivate us (pull us) to perform an action, even in the absence of a corresponding need. REGULATION OF THIRST AND FLUID INTAKE We primarily lose water by urinating, sweating, and breathing. We consciously experience thirst when there is either 1) not enough water inside cells (osmometric thirst) or 2) not enough blood (liquid) in our circulatory system (volumetric thirst)  TONICITY (OSMOMETRIC THIRST) Tonicity refers to the relative concentration of dissolved molecules (solutes in solution) on either side of a membrane that is permeable only to the solution, not to the solutes dissolve in it. Diffusion is the process by which molecules move from areas of high concentration to areas of low concentration. Osmosis refers to the movement of a solution (solvent) from areas of high concentration (low tonicity) to areas of low concentration (high tonicity). Thus, tonicity describes the direction solvent will flow across a membrane that is only permeable to the solvent. Isotonic solution: similar concentrations of solute on either side of the membrane. The cell will neither gain nor lose water. Hypotonic solution: solute is less concentrated outside the cell than in, so water will enter the cell. Hypertonic solution: solute is more concentrated outside the cell than in, so water will leave the cell. BODY FLUID COMPARTMENTS Water freely moves in and out of cells, going wherever the tonicity (the concentration of dissolved solutes) is higher. Cells take in salts and other solutes as needed from extracellular fluid. Across time, intracellular solute concentrations are fairly stable, while extracellular solute concentrations vary according to what we eat and drink. When we drink water, it lowers the tonicity of extracellular fluid, causing cells to expand in size as water moves into them from the extracellular fluid. Excess water is quickly eliminated by urine production. When we consume salt, it increases the tonicity of extracellular fluid, causing cells to shrink in size as water moves out of them. This physical contraction of cells triggers osmometric thirst.  OSMOMETRIC THIRST Hypertonic (salty) solutions cause cellular dehydration (cells lose water and shrink in size). Osmoreceptors are neurons whose membrane potential is sensitive to the size of the cell. The release of neurotransmitter from osmoreceptors relates to the volume of these cells.  VOLUMETRIC THIRST Volumetric thirst occurs when there is not enough blood circulating in the body. The heart needs a certain amount of blood to keep beating. People feel an intense thirst after they lose a lot of blood because of volumetric thirst. Low blood pressure causes cells in the kidneys to release an enzyme called renin, which initiates a cascade of chemical reactions in the blood.  THIRST Feelings of thirst relate to neural activity in a few different brain regions, particularly a hypothalamic area known as anteroventral tip of the third ventricle (the AV3V region). In human fMRI studies, feelings of thirst activate neurons in the AV3V region as well as anterior cingulate cortex. The act of drinking immediately quenches feelings of thirst, and some thirst related neural activity immediately dissipates upon drinking (before water reaches the relevant cells), but AV3V neurons generally remain active until the water reaches them (long after people have stopped drinking). Cold sensors in the mouth and sensory fibers in the stomach are part of the rapid satiety feedback mechanism. The main satiety mechanism may be a learned association between the act of drinking and the dissipation of thirst. Hunger and Feeding Hunger and Feeding Food mostly consists of: Sugars (carbohydrates) Lipids (triglycerides) Amino acids (proteins) Blood Glucose The pancreas monitors blood glucose levels. When blood glucose is high, the pancreas releases insulin. When blood glucose is low, the pancreas release glucagon. Insulin causes blood glucose to be stored as glycogen (in liver and muscle cells). Glucagon causes glycogen to be broken down into glucose. Glycogen (sometimes referred to as animal starch) represents our short-term storage of glucose. We build up glycogen levels when we eat (when insulin is released). We deplete glycogen levels between meals. Glycogen can store up to 2000 calories.  Cells absorption of glucose Cells in the brain can always take in glucose (using a glucose transporter). Most cells outside the brain use a glucose transporter that requires insulin to be functional, which means they can only take in glucose when insulin is present (when blood glucose levels are high). In the absence of insulin (about 2 hours after a meal), cells in the body cannot take in glucose. They can only ketones (made from fatty acids) for energy.  Blood Lipids Fatty acids Triglycerides (lipid) (Adipose tissue) Insulin causes fatty acids to be stored as triglycerides in adipose tissue (fat cells). Triglycerides represent our long-term storage of energy. Glucagon causes triglycerides to be broken down into fatty acids. 1 triglyceride = 1 glycerol molecule + 3 fatty acids The liver converts glycerol into sugar and fatty acids into ketones. In the presence of insulin (top half of figure), all cells can use glucose for energy. Glucose is also stored for later use. In the presence of glucagon (bottom half), glycogen is broken down into glucose for cells in the brain, while cells in the body switch to using ketones (from fatty acids) for energy. Energy Homeostasis System Cells in the liver monitor glucose levels, and this information is brought to the brain by the 10th cranial nerve (the vagus). One controller of hunger is blood glucose levels. But there are many other factors. The stomach releases different signaling molecules when empty and when full. Some of these signaling molecules reach the brain and influence hunger.  SIGNALS FROM THE STOMACH An empty stomach is communicated to the brain by the stomach’s release of a peptide called ghrelin. Levels of circulating ghrelin increase with hunger and fall with satiation. Exogenous administration of ghrelin increases hunger and food intake.  SIGNALS FROM THE STOMACH Swelling of the stomach can slightly reduce hunger, but it mostly just causes a bloated feeling. More important are the peptides that are released by the stomach and intestines when food is consumed. The hormones CCK and GLP-1 regulate the release of digestive enzymes and insulin. They are released by the intestines in proportion to the number of calories ingested, and their entry into the brain elicits feelings of satiety. Repeated administration of CCK to healthy people does not reliably cause sustained weight loss. It sometimes decreases meal size, but people typically respond by eating small meals more frequently. In contrast, GLP-1 agonists have recently proven to be highly effective in reducing hunger and weight in most people. These drugs were initially developed to boost insulin signaling in diabetics.  LONG-TERM FAT STORAGE Beyond monitoring blood glucose and food in the stomach, the body also monitors fat levels. The body wants to ensure there is enough fat to make it between meals. In many cases, when a healthy animal is force-fed so that it becomes heavier than normal, it will reduce its food intake once it regains control over how much it eats. Signals that come from fat cells Leptin is a circulating hormone that is secreted by adipocytes (fat cells). Leptin levels correlate with the amount of fat in the body. As fat cells grow and proliferate, leptin levels increase. If leptin levels fall below some threshold, animals feel intense hunger. To some extent, leptin levels regulate the sensitivity of hypothalamic neurons to short-term satiety signals (e.g., CCK and GLP-1). Exogenous administration of leptin can slightly decrease meal size in healthy people, but this effect is short-lived. However, exogenous leptin administration is a lifesaver for people who are unable to produce leptin due to a genetic mutation.  Congenital leptin deficiency Before treatment, After years of daily 3 years old. injections of leptin, 7 years old. Ob mouse - Strain of mice whose obesity and low metabolic rate are caused by mutation that prevents production of leptin  EMERGENCY HUNGER CIRCUITS Emergency hunger circuits are activated when a specific critical need to eat or not eat overrides energy homeostasis circuitry. Glucoprivation Dangerously low blood-glucose levels (i.e., not enough (hypoglycemia) immediately available sugar in the blood) can cause intense hunger Glucoprivation can result from excessive insulin signaling and from drugs that inhibit glucose metabolism Lipoprivation Dangerously low levels of fat (i.e., not enough fat on the body or free fatty acids in the blood) Can be caused by drugs that inhibit fatty acid metabolism  Emergency Hunger When the brain senses that energy stores are dangerously low (glucoprivation or lipoprivation), it launches an emergency cascade of effects: Insulin release is suppressed, and glucagon release is triggered. Short-term satiety signals are ignored. Energy expenditure slows (basal metabolic rate), halting growth and reproductive systems A potent and sustained feeling of hunger takes hold  Diabetes Diabetes is a condition where people are either insensitive to insulin signaling or they do release enough insulin. Diabetes results in high blood glucose levels and an inability to store glucose as fat.  If left untreated, it leads to intense thirst and progressive weight loss (especially for type 1 diabetes, in which insulin is not being released).  As fat cells become depleted, leptin levels fall, and a lipoprivation- related feeding emergency takes hold, resulting in intense hunger, even if there is tons of glucose in the blood.  This situation often led to death before insulin treatments were discovered 100 years ago. Hypothalamus The hypothalamus is a key regulator of hunger. Two cell populations in the arcuate nucleus of the hypothalamus have opposing influences on hunger. Stimulation of one cell population – the neurons that co-release the peptides AGRP and NPY – causes dramatic overeating. Leptin and other satiety signals inhibit these neurons. Arcuate Nucleus of the Hypothalamus AGRP/NPY neurons promote hunger. They are inhibited by leptin and activated by ghrelin. Neighboring (POMC) neurons inhibit hunger. They are activated by leptin and inhibited by ghrelin. Feelings of hunger partially relate the balance of activity between these two cell populations, but many other factors are relevant. These two cell populations project to the paraventricular nucleus (PVN) of the hypothalamus. Some neurons in this area stop firing when the body has dangerously low levels of fat (leptin). Paraventricular Nucleus (PVN) of the Hypothalamus Artificially increasing PVN neuron activity does not substantially/reliably change hunger, but the inhibition of some cells in this area can generate intense hunger. These cells seem to trigger a lipoprivation response. Prader-Willi Syndrome Prader-Willi syndrome is a rare chromosomal abnormality in which up to 7 genes are deleted from chromosome 15. One of these genes is critical for the development/survival of a population of PVN neurons. People with Prader-Willi syndrome are born with very low muscle mass and have little interest in eating. But between 2 and 8 years of age, they develop a heightened, permanent and painful sensation of hunger, a feeling of starving to death. Average life expectancy in the United States is 30; most die of obesity- related causes. People with this disorder have no sensations of satiety to tell them to stop eating or to throw up, so they can accidentally consume enough food in a single binge to fatally rupture their stomach. There was an interesting profile of Prader-Willi syndrome in the New York Times. The Modern Obesity Epidemic About 50% of the variability in people’s body fat is due to genetic differences. Natural variations in metabolic efficiency are one of the most important factors. Our world is clearly changing much faster than our genes are, and some people’s genes are not well-suited to our current food environment. There is a hedonic aspect to hunger. Food can be delicious and reinforcing even when people are not hungry. But this is truer for some people than others. Some people think about food constantly, even when they have sufficient stores of energy. Neuroscientists have not made much progress in understanding why, but they are using the hormones released by the gut (such as GLP-1) as tools to study neural control of hunger.  SURGICAL TREATMENT FOR OBESITY Beyond pharmacological treatments to control weight, surgeries have developed that limit the amount of food that can be eaten during a meal. Bariatric surgery modifies the stomach, small intestine, or both. The most effective form is called the Roux-en-Y gastric bypass (RYGB). With RYGB surgery, the second part of small intestine (the jejunum) is cut and attached to the top of the stomach. The stomach is also stapled to make it much smaller. This surgery often results in reductions in hunger over time, but it is not clear why this happens. Changes in hunger do not seem to correlate with any observed changes in hormone signaling from the stomach.