Physiological Basis of Hunger: Neural Control

Module 1: Physiological Basis of Hunger

Neural Control of Food Intake

• Energy intake must match energy expenditure to maintain stable body mass and composition over time.
• Only 27% of ingested energy reaches functional cell systems; the rest is converted to heat through metabolism and physical activity.
• Excess energy is primarily stored as fat.
• A deficit in energy leads to loss of body mass, eventually resulting in death.
• An adequate energy supply is crucial for survival.
• The body uses powerful physiological control systems to maintain adequate energy intake.
• Hunger is triggered by deficits in energy stores.
• Short-term and long-term control systems regulate food intake, energy expenditure, and energy stores.

Role of Hypothalamus

• Several hypothalamic neuronal centers control food intake.
• The lateral nuclei act as a feeding center; stimulation causes hyperphagia (overeating).
• Destruction of the lateral hypothalamus results in a lack of desire to eat.
• Progressive inanition occurs, characterized by weight loss, muscle weakness, and decreased metabolism.
• The ventromedial nuclei serve as the satiety center.
• Complete satiety results from electrical stimulation of the ventromedial nuclei.
• Destruction of ventromedial nuclei causes extreme obesity due to voracious eating.
• The paraventricular, dorsomedial, and arcuate nuclei regulate food intake.
• Lesions of the paraventricular nuclei can cause overeating.
• Lesions of the dorsomedial nuclei depress eating behavior.
• Arcuate nuclei in the hypothalamus are sites where hormones from the gastrointestinal tract and adipose tissue converge to regulate food intake and energy expenditure.
• Chemical cross-talk among neurons in the hypothalamus coordinates eating behavior and satiety perception.
• The nuclei influence the secretion of hormones important for energy balance and metabolism, including those from the thyroid, adrenal glands, and pancreatic islet cells.
• Neural signals from the gastrointestinal tract provide sensory information to the hypothalamus about stomach filling, nutrients in the blood, and gastrointestinal hormones which influence feeding behavior.
• Orexigenic substances stimulate feeding, including Endorphins, Galanin, Cortisol, and Ghrelin.
• Anorexigenic substances inhibit feeding, including Leptin, Serotonin, Norepinephrine, Corticotropin-releasing hormone, Insulin, and Cholecystokinin.

Neural Centers That Influence the Mechanical Process of Feeding

• Centers in the brainstem control the mechanics of feeding.
• Other centers regulate food intake quantity and stimulate feeding mechanics.
• The amygdala and prefrontal cortex control appetite.
• Destruction of certain amygdala areas can increase or inhibit feeding.
• Stimulation of amygdala areas elicits the mechanical act of feeding.
• Amygdala destruction can cause "psychic blindness" in food choice, affecting appetite and food quality selection.

Factors that Regulate Quantity of Food Intake

• Divided into short-term and long-term regulation.
• Short-term regulation primarily prevents overeating at each meal.
• Long-term regulation maintains normal energy stores.

Short-Term Regulation of Food Intake

• Involves rapid feedback signals.
• Gastrointestinal Filling: Distension of the gastrointestinal tract, especially the stomach and duodenum, sends inhibitory signals that suppress the feeding center and reduce the desire for food.
• Gastrointestinal Hormonal Factors: Cholecystokinin is released when fat enters the duodenum, directly reducing subsequent eating.
• Activation of the melanocortin pathway in the hypothalamus may mediate CCK's effects.
• Peptide YY PYY is secreted from the entire gastrointestinal tract, releases food and blood concentrations which rise to peak levels 1 to 2 hours after eating.
• The importance of this hormone in regulating appetite in humans is still unclear.
• The presence of food in the intestines stimulates them to secrete glucagon-like peptide, which increases enhances insulin production and secretion from the pancreas which tends to suppress appetite.
• Ghrelin is released mainly by oxyntic cells of the stomach and intestine.
• Ghrelin levels rise during fasting, peak before eating, and fall rapidly after a meal, suggesting a role in stimulating feeding.

Intermediate and Long-Term Effect of Food Intake

• Blood Concentrations of Glucose, Amino Acids, and Lipids: Decreased blood glucose concentration causes hunger, leading to the glucostatic theory of hunger and feeding regulation.
• Blood amino acid and lipid concentrations have similar effects, leading to aminostatic and lipostatic theories.
• Decreased availability of major food types increases the desire for feeding, restoring blood metabolite concentrations.
• Neurophysiologic studies show that increased blood glucose raises the firing rate of glucoreceptor neurons in the satiety center of the ventromedial and paraventricular nuclei.
• Increased blood glucose level decreases the firing of glucosensitive neurons in the hunger center of the lateral hypothalamus.
• Amino acids and lipids affect the firing rates of these neurons.
• Temperature Regulation: Cold exposure increases feeding, while heat exposure decreases caloric intake.
• The hypothalamus mediates this interaction between temperature-regulating and food intake-regulating systems.
• Increased food intake in cold animals increases metabolic rate and fat insulation.

Summary of Long-Term Regulation

• When energy stores fall below normal, the hypothalamus and other brain areas increase hunger and food-seeking behavior.
• Abundant energy stores lead to a loss of hunger and satiety.

Importance of Having Regulatory Systems for Feeding

• Long-term regulation maintains constant nutrient stores.
• Short-term regulatory stimuli:
  • make the person eat smaller quantities allowing for a slow pace through the gastrointestinal tract.
  • aids in the prevention of too much food, which is not suitable for metabolic storage systems.

Obesity

• Defined as excess body fat.
• Body mass index (BMI) is used as a substitute marker for body fat content.
• BMI = weight in kg / height in m².
• Overweight: BMI between 25 and 29.9 kg/m².
• Obese: BMI greater than 30 kg/m².

Causes of Obesity

• Greater Energy Intake than Expenditure: Excess energy is stored as fat.
• Excess energy intake in children leads to hyperplastic obesity, with increased adipocyte numbers.
• Obesity in adults increases adipocyte size, resulting in hypertrophic obesity.
• Decreased Physical Activity and Abnormal Feeding Regulation: Lifestyle and environmental factors contribute.
• Regular physical activity increases muscle mass and decreases body fat, whereas inadequate physical activity is associated with decreased muscle mass and increased adiposity.
• Muscular activity expends energy, and increased physical activity often reduces fat stores.
• Environmental, Social, and Psychological Factors: Abundant high-energy foods and sedentary lifestyles contribute to prevalence in industrialized countries.
• Psychological factors, for example stress can contribute to obesity.
• Eating as a means of releasing tension.
• Childhood Over-nutrition
• Neurogenic Abnormalities: Lesions in the ventromedial nuclei of the hypothalamus cause excessive eating and obesity.
• Hypophysial tumors that encroach on the hypothalamus can cause obesity.
• Neurotransmitter changes in the hypothalamus can results in increased hunger
• Genetic Factors: abnormalities in the feeding centers, energy expenditure, and fat storage can lead to obesity.
• Monogenic causes of obesity: Mutations of MCR-4 is the most common, mutations of the leptin gene, and mutations of the leptin receptor.
• All monogenic forms of obesity account for only a small percentage of obesity.

Treatment of Obesity

• Decrease energy input below energy expenditure to achieve a sustained negative energy balance.
• Amphetamines reduce hunger.
• Drugs alter lipid metabolism, causing fat loss in feces.
• Increased physical activity leads to weight loss.
• Common surgical procedures: Gastric bypass surgery and Gastric banding surgery
• Gastric bypass surgery involves construction of a small pouch that is then connected to the jejunum.
• Gastric banding surgery involves placing an adjustable band near the upper end, creating a small stomach pouch that limits the amount of food that can be eaten at each meal.
• Uncertain long-term effects

Eating Disorders

• Inanition: Opposite of obesity and characterized by extreme weight loss. Caused by inadequate food availability or conditions reducing the desire for food, such as psychogenic disturbances or hypothalamic abnormalities.
• Anorexia: A reduction in food intake caused primarily by a diminished appetite.
  • Anorexia nervosa: An abnormal psychic state in which a person loses all desire for food and is nauseated by food.
    • Binge/Purge Type: Purging after eating. -Restrictive: Limiting the quantity of food consumed, effectively slowly starving.
• Bulimia Nervosa: A severe life-threatening psychological and severe life-threatening eating disorder described by the ingestion of an abnormally large amount of food in short time period, followed by an attempt to avoid gaining weight.

Module 2: Physiological Basis of Thirst

Peripheral Factors in Water Regulation

• Thirst arises from water deprivation.
• Dryness in the mouth, throat, mucous membrane, and pharynx.
• Thirst functions as a need or drive resulting from liquid deprivation.
• The Hippocrates dry mouth theory states that air passing over throat membranes causes creation of the sensation of thirst.
• Walter Cannon's dry mouth theory says drinking results from dry mouth as well as salivary gland function and moisture receptors in the mouth.
• Cultural and social factors also influence drinking patterns.
• Summer thirst intensifies to conserve water.
• Host Factors are influenced by cold and hot training sessions, exercise, frequent rest periods, and learned behaviors.
• Elderly men experience a blunted thirst drive and reduced fluid intake because of reduced brain sensitivity to blood volume changes. Additionally, kidney's ability to conserve water is reduced.

Central Factors in Water Regulation

• There are two types of thirst, osmotic and hypovolemic.
  • Osmotic thirst is caused by eating salty food.
  • Hypovolemic thirst is induced by loss of fluid by bleeding or sweating.

Osmotic Thirst/ Cellular Dehydration Thirst

• Thirst is caused to loss of water from the osmoreceptors.
• Solute concentration remains at .15M(molar) in the body which serves as a set point.
• Osmotic pressure is the tendency of water to flow from low to higher concentration across a semipermeable membrane.
• Water is able to pass through the semipermeable membrane and solute is not.
• Osmotic pressure occurs when solutes are more concentrated on one side of the membrane than the other.
• Intake of something salty increased sodium tons throughout blood and extracellular fluid but do not cross the membrane to cells.
• The imbalance of solutes in the cell and outside the cell draws water out the cells into the extracellular fluid.
• Receptors relay information in the OVLT, SFO, the stomach which relay their information to the several parts of the body.
• Certain neurons detect their own lose of water and trigger osmotic thirst in order to restore normal state.
• The kidneys increase concentration of urine to get rid of excess Na+ and maintain as much water as possible.
• Important areas for detecting osmotic pressure and salt content in blood: OVLT (Organism VasculasmLaminiTermilaris) and SFO (SubformicalOrgan).
• The OVLT receives signals from digestive tract receptors to anticipate osmotic needs.
• The body measures swelling of the stomach and upper small intestines and the messages limit drinking and keep only the necessary hydration.

Hypovolemic Thirst

• Thirst occurs if the body loses fluid through bleeding, diarrhea, or sweating, even as osmotic pressure remains constant.
• Pumping blood to the head becomes troublesome and nutrient distribution becomes less efficient.
• Vasopressin and Angiotensin 2 constrict the blood vessels.
• The kidneys release the enzyme renin to increase the formation of angiotensin.
• Angiotensin helps trigger thirst in conjunction with receptors that detect blood pressure in the large veins.
• This helps encourage the restoration of lost salt and water.
• Known as hypovolemic thirst, which is based on low volume.
• The body cannot afford to drink pure water as it will dilute the body fluid and it needs salty fluid.

Module 3: Physiological Basis of Sexual Behavior

Hormones and Sexual Development

• Fetal Hormones and Development of Reproductive Organs
• At the beginning stage of development, each foetus possesses the same pair of gonadal structures named primordial gonads.
• Each primordial gonad has the possibility to be an outer covering, named cortex, with the capacity to develop into an ovary, each has a inner core named medulla, with the possibility to develop into a testis.
• The Sry gene causes the synthesis of Sry protein in males, leading to the development of testis.
• In absence of Sry protein, the cortical cells of the primordial gonads automatically develop into ovaries.
• Six weeks after fertilization, both males and females have two sets of reproductive ducts. They have a male Wolffian system, which can develop into the male reproductive ducts and a female Müllerian system, which can develop into the female ducts.
• Testes secrete testosterone and Müllerian-inhibiting substance in the third month of male fetal development.
• Testosterone stimulates the growth of the Wolffian system, Müllerian-inhibiting substance causes the Müllerian system to degenerate and the testes to descend into the scrotum.
• The development of the Müllerian system occurs in any fetus that is not exposed to testicular hormones.
• Ovariectomy: Removal of the ovaries
• orchidectomy: Removeal of the testes
• Gonadectomy: Surgical removal of gonads (either ovaries for testes).
• Male and female genitals develop from the same precursor known as bipotential precursor.
• external genitals is guided by the prescence or absence of testosterone.
• Sex Differences in Brain
• Men are prone to have 15% larger in brains
• Studied in nonhuman mammals
• Control the release of gonadotropin in males and females

Perinatal Hormones and Behavioral Development

• Testosterone injection causes genetic females adult to display copulatory behavior.
• Phoenix found that female that were exposed to exposure to perinatal testosterone were found to have male-like mounting behavior than the other in adulthood.
• Guinea pigs displayed less lordosis.
• Lack of early exposure of male rats to testosterone both feminizes and demasculinizes their copulatory behaviour as adults.
• Rats failed to have copulatory pattern of mounting after birth when treated w testoserone
• The aromatization is important both the feminization as well masculinization.

PUBERTY: HORMONES AND DEVELOPMENT OF SECONDARY SEXUAL CHARACTERISTICS

• Levels of certain hormones are low.
• Period ends during the onset of puberty in which secondary characteristics develop.
• These are features which other than the reproductive organs which distinguish sexually mature women and women.
• Puberty- hormones by the anterior pituitary are released.
• The release of growth hormone impacts bone and muscle tissue.
• Puberty begins at about 10.5 years of age for girls and 11.5 years for boys.
• Androstenedione is normally responsible for underarm hair in women.

EFFECTS OF GONADAL HORMONES ON ADULTS

• Male Reproduction:
• orchidetomized: Cases of 157 reviewed, it was agreed that there was a reduction in the length of prison terms. the study leads to a reduction in sex interest and behavior.
• Orchidectomy removes glands that release many hormones
• The amount of testosterone he level of a man's sexuality is a function of
• False One's sex drive can be increased by increasing testosterone.
• Dihydrotestosterone failure to copulatory behavior
• The restoration of copulatory by testosterone in primates occurs by different mechanisms.
• Female Repruction*- mature female rats and Guinea pigs produce 4 day cycles a gonadal hormone release.
• Surge in progesterone and estrogen in estrus for almost 12 to 18 hrs.

Neural Mechanisms of Sexual Behavior

• Structural Differences between Male and Female Hypothalamus
  • Hypothalamus functionally differently
    • Difference in the male and female hypothalamus were found and discovered in rats.
    • Gorski- a nucleus in the media preoptic area of the rat hypothalamus which was severally larger in the male
    • Named sexually dimorphic nucleus, same at birth.
    • Bilateral Lesions: disrupted effeorts in the sexual behavior.
    • Differ in men and women.

Hypothalamus and Male Sexual Behavior

• The medial preoptic area controls in behaviour
  • Destruction removes behaviour studied
  • Bilateral medial preoptic lesions- Copulatory behavior
    • Appears to control behaviour in a tract lateral tegmental field - This disrupts behavior

Module 4: Neural Basis of Emotion

Role of Frontal Lobes

• Damage can cause a reduction in emotional feelings
• Abstract thinking and self-awareness.
• Front region of the lobe is referred to as the prefrontal cortex.
• input from amygdala
• damasio and eslinger- orbitofronal cortex. It doesnt necessarily translate judgements but appropriate feelings and behaviors.

Prefrontal Cortex

• Integrates information from the past and current
• Somatic marker signaling Emotions that elicit moving towards or avoiding Behavior associated with activation or behavior Under-activity is PFC with depression and withdrawl Goal direction and rewards work within PFC Depression is inability to control behavior Right PFC is active in negative moods

Behavioral Functions of Hypothalamus

• Range of emotions
• Stimulation role comes from different nuclei that are formed
• Study by Heess
  • certain areas stimulation of a two related effects - Triggering attacks - sympathetic system - contrast of hypothamlic region which trigger behavior during slow heartrate
  • Affective region of aggressive involving the medial hypothalamus
    • based on studies- state reduce -not aversive
      • support to hypothesis in emotion
        • tumor
    • portions of the hypothalmus reported to have a calming effect

Behavioral Functions of Limbic System

• concerned with the affective nature of sensory sensations-that is, whether the sensations are pleasant or unpleasant
  • affective/rewarding/ satisfying/ rewarding