Hypothalamus

The hypothalamus

the body’s health management system

• controls ANS (visceral response)

• controls endocrine system (hormones)

• contributes to behavior (motor system)

Hypothalamus - Controlling ANS (visceral response)

• homeostasis (body temperature - shiver, sweat, blood volume, glucose levels)

• sympathetic (“fight or flight” - increase hear rate, depressed digestion, mobilize glucose)

• parasympathetic (decrease heart rate, activate digestion)

Hypothalamus - controls endocrine system (hormones)

• mobilize energy stores

• ovulation & spermatogenesis

• stimulate growth, milk secretion

Hypothalamus - contributes to behavior (motor system)

• feeding

• sleep

• circadian rhythms

• s3xual behavior

• emotion & fear

Modes of communication by the hypothalamus

• motor system

• neuroendocrine system

• ANS

Motor system

point to point, specific, brief, fast

Neuroendocrine system

release of hormones into blood stream. slow, widespread

ANS

lots of interconnections within the body to control many organs, blood vessels, and glands simultaneously

Anterior pituitary gland

• adrenocorticotropin hormone (ACTH) thyroid-stimulating hormone

• growth hormone

• prolactin

• luteinizing hormone (ovulation, helps hormone production during pregnancy)

• melanocyte-stimulating hormone (MSH) (protects skin from UV light, controls pigmentation, and appetite)

Posterior pituitary gland

• oxytocin (lactation, feeling of bonding)

• Antidiuretic hormone (ADH or vasopressin)

Pathways to the posterior Pituitary

Two neurohormones:

• oxytocin

  • lactation, bonding

• vasopressin or antidiuretic hormone (ADH)

  • regulates blood volume and salt concentration, parental/partner bonding

Hypothalamic Control of the Posterior Pituitary: ADH

1. low water intake —> low blood pressured

• pressure receptors in the cardiovascular system

• salt receptors in the hypothalamus

2. Vasopressin (ADH) is released —> leads to water retention by kidneys

3. Kidneys release renin

4. Angiotensin II is produced and sensed at Subfornical organ

5. Angiotensin II leads to more release of ADH and activation of lateral hypothalamus

Hypothalamic Control of the Anterior Pituitary

• controlled by parvocellular neurosecretory cells

• secrete hypophysiotropic hormone

• bind to specific receptors on pituitary cells

• receptor activation: pituitary cells secrete or stop secreting hormones

• hypothalamo-pituitary portal circulation

The stress response: CRH and cortisol

• when cortisol is low, the hypothalamus secretes CRH, which stimulates the pituitary to release ACTH (adrenocorticotropic hormone). ACTH then acts on the adrenal cortex to trigger cortisol release

• cortisol helps manage stress by increasing blood glucose, reducing inflammation, and regulating energy use. Rising cortisol levels send feedback to the brain to suppress CRH and ACTH, maintaining balance

Robert Sapolsky’s study of baboons findings

• Subordinate, lower ranking males were hypercortisolemic - they had elevated levels of cortisol in their blood. High-ranking baboons tended to have lower levels of cortisol

• In one year (1981), 6 males formed an alliance to remove the highest ranking male. They succeeded, but then all six fought with each other to get the top spot. During this tumultuous time of instability in the troop, these dominant males’ cortisol concentrations were has high as subordinates

• In 1984 there was a massive drought in the Serengeti and food became scarce. While their body weight stayed the same and they managed to survive the drought, the baboons had to work much harder to find food and stay alive. This led to a 78% reduction in aggression. It also led to drops in cortisol levels of the subordinate males. The high-ranking males still had lower levels (slightly), but the difference between the two groups was the smallest over the 6 years of study

Situations and reactions that lower levels of cortisol

1. Social support

2. Displaced aggression

3. Ability to detect threat

4. Asserting control

5. Knowing when you’re beaten

Stress in males and females

• Women are more likely than men (28% vs 20%) to report having a great deal of stress (8,9, or 10 on a 10-point scale)

• Almost half of all women (49%) surveyed said their stress has increased over the past five years, compared to four in 10 (40%) men

Hypothalamic control of emotional arousal and consequences on feelings

• Two arms of stress response

  • epinephrine: released rapidly from the adrenal medulla via the sympathetic nervous system (“fight-or-flight”)

  • cortisol: released more slowly from the adrenal cortex via the HPA axis (hypothalamus —> pituitary —> adrenal)

The Suspension Bridge Study (Dutton & Aron, 1974)

Design:

• male participants encountered a female (or male) interviewer either:

  • On a high, shaky suspension bridge (which induces physiological arousal), or

  • On a low, stable bridge (less arousal)

• The interviewer gave the men a questionnaire and her phone number “for follow-up)

Findings:

• Men interviewed on the high bridge were significantly more likely to call the female interviewer and wrote more sexually charged stories on the questionnaire

• Interpretation: the men misattributed their heightened physiological arousal from fear as sexual attraction

Role of insulin controlling sugar

1. After a meal, carbohydrates are broken down into glucose, which enters the bloodstream

2. Rising glucose triggers the pancreas to release insulin

3. Insulin binds to receptors on liver, muscle, and fat cells, allowing glucose to enter

4. Cells then use glucose for energy or store it as glycogen

5. When glycogen stores are full and there is excess glucose, the body converts excess glucose into triglycerides, storing them as body fat when total calorie intake exceeds energy expenditure

6. Dietary fat (mainly triglycerides) is broken down into fatty acids through digestion and cellular metabolism

By promoting glucose uptake…

insulin lowers blood sugar and keeps it within a healthy range. If insulin is insufficient or ineffective (as in diabetes), blood glucose remains elevated

Does the brain require insulin to let glucose inside neurons?

The brain does not require insulin to let glucose inside neurons, but insulin binds to receptors in the hypothalamus and signals energy abundance

Parabiosis

shared blood supply

• normal + obese

Leptin

released into blood by fat cells

• obese mouse + leptin = normal

Control of feeding by hypothalamus

• Arcuate nucleus

  • can sense leptin levels

  • controls paraventricular nucleus

  • controls lateral hypothalamic area

• Paraventricular nucleus

  • ANS

  • endocrine system

• Lateral Hypothalamic Area

  • motor response (feeding)

Case 1 — high leptin levels (lots of fat!)

• leptin receptors in neurons of arcuate nucleus

• these arcuate nucleus neurons release peptides aMSH, CART

• aMSH, CART inhibit neurons in lateral hypothalamus that activate feeding behavior

• aMSH, CART also activate neurons in the paraventricular nucleus that activate endocrine and ANS responses

Anorectic

pathways that stop eating

Leptometer (high leptin)

• CART and aMSH is released

• stops sending information to the lateral hypothalamus

• sends information to the paraventricular nucleus

  • sympathetic NS is activated:

    • increase energy expenditure

    • activation of thyroid gland

Case 2 — low leptin levels (fat needed!)

• arcuate nucleus neurons release peptides NPY, AgRP

• NPY, AgRP activate neurons in lateral hypothalamus that activate feeding behavior

• NPY, AgRP inhibit neurons in the paraventricular nucleus that activate endocrine and ANS response

Orexigenic

pathways that promote eating

Leptometer (low leptin)

• AgRP and NPY are released (activated by ghrelin)

• stops sending information to the paraventricular nucleus

• sends information to the lateral hypothalamus

  • activates melanin-concentrating hormone (MCH) which is a neuropeptide (promotes appetite)

  • activates motor systems, cortex, and brainstem (FEEDING BEHAVIOR)

Short-term control of feeding

• Triggers parasympathetic response (salivation, mobilization of digestive enzymes)

• Empty stomach releases ghrelin, which activates NPY and AgRP-containing cells

• Distended stomach also activates nucleus of the solitary tract (via vagus), inhibiting feeding behavior

• After eating too much, CCK from intestines (via vagus), insulin from pancreas (via hypothalamus) signal satiety

Insulin acts as a signal of energy abundance, NOT for glucose uptake

How does Ozempic work?

Ozempic, also known as semaglutide, helps people manage type 2 diabetes and sometimes weight by mimicking a natural hormone in the body called GLP-1 (glucagon-like peptide-1). This hormone is normally released after eating and has several helpful effects:

• Increases the release of insulin from pancreas when blood sugar is high, which helps lower blood sugar levels

• Reduces the amount of another hormone, glucagon, that tells the liver to release more sugar into the blood

• Slows down how quickly food leaves the stomach, so sugar enters the bloodstream more gradually

• Affects the brain to reduce hunger, which helps many people lose weight

Eating disorders

• Anorexia

• Bulimia

Both are affected by cultural bias and psychological factors

Anorexia

• alterations in Ghrelin and NPY/AgRP

• genetic components

• alterations in DA system

Bulimia

• genetic vulnerability

• altered serotonin/dopamine signaling affecting mood, impulse control, and appetite

Other systems playing a role in hunger, satiety, and behavior

• Endocannabinoid systems

• Gut microbiota (microbiome)

• Treatment: fecal transplant

Endocannabinoid system

cannabis stimulate hunger. Endogenous cannabinoids, such as anandamide stimulate hunger when injected in the hypothalamus

Gut microbiota (microbiome)

body contains 2.5-5 pounds of gut microbes (bacteria, viruses, fungi) making more than ½ of the contents of large intestine. Alterations in gut microbiota influence mood, cognition and social behavior. associated with autism, schizophrenia, bipolar disorder, multiple sclerosis, Parkinson’s disease, and obesity