Neuroscience Test 2, Hypothalamus

  1. Common causes of hypothalamic lesions
    • Hypothalamic/pituitary tumors, head trauma, alcoholism, aging, self-antibodies, genetic abnormalities, and long-term extremes (such as starvation or obesity)
    • Rarely affected by strokes due to rich blood supply
  2. Signs of hypothalamic lesions
    Mood changes, weight problems, changes in appetite or drinking, insomnia/hypersomnolence, altered body temperature, dramatic changes in serum chemistry, changes in sexual behavior, or delayed/precocious development
  3. General function of hypothalamus
    • Maintain homeostasis of body
    • This includes regulating body temp/febrile response; food, salt, and water intake; sexual cycles, sexual orientation, and onset of sexual milestones; circadian rhythms; sleep; body weight; and stress response
    • The hypothalamus consists of gray matter in 15-20 nuclei
  4. Where are key hypothalamic landmarks located?
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    • Lamina terminalis: A non-nervous structure that marks the anterior limit of the developing brain
    • Posterior limit: An imaginary line from the mammillary bodies to the posterior commissure
    • Lateral boundaries are vague
  5. Paraventricular nucleus
    • Found near to the IIIrd ventricle
    • Interfaces with the endocrine and autonomic systems
    • Most connections/most important!
  6. Supraoptic nucleus
    • Located just above the optic tract
    • An important area for the release of vasopressin (similar to paraventricular nucleus)
  7. Suprachiasmatic nucleus
    • Located on the midline above the optic chiasm
    • Generates circadian rhythms
  8. Sexually dimorphic nuclei
    • Located in the anterior hypothalamus
    • These nuclei are possibly involved in sexual orientation and differ in their shape and cell number between men, women, and gay men
  9. Arcuate nucleus
    • Located on either side of the IIIrd ventricle
    • Involved in appetite and consumption
  10. Preoptic nuclei
    • Located anterior to the optic chiasm
    • Involved in thermoregulation, salt water intake, and sleep
  11. Lateral and tuberal groups of nuclei
    Shown on the outside of the hypothalamus as a tubercineum, or a grey matter bump
  12. Main hypothalamic white matter bundles
    • Fornix: Connects mammillary bodies with the hippocampal formation (these fibers are affected in Korsakoff's syndrome)
    • Medial forebrain bundle: Runs through the lateral hypothalamus that connects the amygdala and basal forebrain with the midbrain; lesions affect appetite
    • Mammillothalamic: Links mammillary bodies with anterior thalamus
    • Mammollotegmental tract: Links mammillary bodies with dorsal midbrain
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    • Tuberoinfundibular tract: Connects the underside of the hypothalamus with the pituitary gland via infundibulum/pituitary stalk; damaged when displacement of brain in head trauma
  13. Bitemporal hemianopsia
    • Tunnel vision
    • Often resulting from hypothalamic or pituitary tumors compressing the optic chiasm
  14. Neural inputs to hypothalamus
    • Retina: Retinal ganglion cells send axons to suprachiasmatic nucleus to generate circadian rhythms
    • Olfactory: Mostly indirect input to hypothalamus
    • Somatosensory: Mostly thermal and nociceptive information conveyed directly by part of the spinothalamic system, the spinohypothalamic pathway; additional information arrives indirectly through the reticular formation
    • Visceral afferents: 70% from vagus, carrying information about GI, liver, abdominal viscera, and baroreceptors/chemoreceptors of heart and carotids via axons arising in the nucleus of the solitary tract in the dorsal medulla
    • Input also from medial/orbital frontal cortex, insula, amygdala, and hippocampal formation (to mammillary bodies)
  15. Chemosensory inputs to hypothalamus
    • Hypothalamus itself: Many hypothalamic neurons are sensitive to circulating metabolites (glucose), osmolality, long-chain fatty acids, and temperature; mostly use malonyl coenzyme A as an intracellular sensor
    • Hormone and steroid receptors: Most hypothalamic neurons have hormone receptors in order to respond to hormones released by the pituitary (ultra-short feedback loop), adipose tissue (leptin), or the gut (cholecystokinin)
    • Circumventricular organs: Subfornical organ (sensitive to CSF angiotensin II) and organum vasculosum of the lamina terminalis (sensitive to serum osmolality)
    • The median eminence is also a circumventricular organ in the hypothalamus that is thought to be important in uptake of hormones, peptides, and signaling molecules. It is also the site of release of hormones into the hypothalamo-hypophyseal portal system of blood vessels
  16. Major overview of outputs of the hypothalamus
    • Anterior pituitary:
    • Posterior pituitary:
    • Preganglionic autonomic efferent neurons:
    • The hypothalamus also sends axons throughout the cerebral cortex adn to teh basal forebrain and amygdala, connections that are presumed to alter motivated behavior and are involved in wakefulness
  17. Hypothalamic outputs to the anterior pituitary
    • The hypothalamus releases releasing hormones through the median eminence into the hypothalamo-hypophyseal portal system
    • These releasing hormones are produced in the paraventricular nucleus and in scattered groups in the medial and ventral hypothalamus
  18. Hypothalamic outputs to the posterior pituitary
    Magnocellular neurons in the paraventricular and supraoptic nuclei synthesize vasopressin and oxytocin. Their axons travel in the infundibulum in the tuberoinfundibular tract to the posterior pituitary, where the hormones are released through fenestrated capillaries directly into the circulation of the posterior pituitary
  19. Diabetes insipidus
    Caused by damage to the infundibulum resulting in no release of vasopressin and excretion of large volumes of urine (polyuria), increased thirst, and excessive water drinking (polydipsia)
  20. Hypothalamic influence over the autonomic nervous system
    • Parasympathetic preganglionic neurons: Projections go directly to the midbrain (Edinger-Westphal), pons and medulla (salivatory nuclei, nucleus ambiguus, dorsal vagal nucleus), and the sacral cord (S2-S4)
    • Sympathetic preganglionic neurons in spinal cord: Cause control of the adrenal medulla and adrenaline/noradrenaline release
    • Autonomic pattern generators: In the pons and medulla
  21. Basic operational organization of the hypothalamus
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  22. What regions of the hypothalamus are most connected to autonomic areas?
    • Paraventricular nucleus (most important), arcuate and ventromedial nuclei, and lateral hypothalamus (in fact, the lateral hypothalamus effects the whole brain also, controlling sleep, receiving food intake information, etc)
    • The hypothalamospinal pathway is an effector on sympathetics
  23. Hypothalamospinal pathway
    • Passes through the midbrain and pontine tegmentum and the lateral part of the medulla in the central tegmental tract
    • Lesion of this pathway leads to Horner's syndrome, which is present in lateral medullary sydrome
  24. Temperature control in the hypothalamus
    • Warm-sensitive neurons are in the medial preoptic region of the anterior hypothalamus and activate the endocrine/autonomic activity of the paraventricular nucleus and inhibits a medullary thermogenic center in the nucleus raphe pallidus via GABA
    • The nucleus raphe pallidus controls cardiovascular, skin, and adrenal function via the sympathetic system
    • Increases in core temperature: Inhibition of raphe neurons and activation of endocrine/autonomic responses such as sweating, decreased metabolism, and vasodilation
    • Decreases in core temperature: Activate neurons in the dorsomedial/posterior hypothalamus, which are excitatory to raphe neurons and cause sympathetic responses of skin vasoconstriction, shivering and piloerection, and increased metabolism
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  25. Hypothalamic lesions affecting body temperature
    • Anterior hypothalamus: Hyperthermia
    • Posterior hypothalamus: Hypothermia or a body temperature matching the ambient temperature
  26. Febrile response
    • Warm-sensitive neurons in the anterior hypothalamus are sensitive to pyrogens (such as bacterial endotoxins or interleukins), and activate thermogenesis by raising the set point
    • This occurs by production of prostaglandin E2 production in the capillary walls which binds the EP3 receptor on medial preoptic neurons, activating thermogenesis by inhibiting the preoptic warm-sensitive, inhibitory neurons from firing
    • NSAIDS, indomethacin, etc inhibit cyclo-oxygenases 1 and 2 that make prostaglandins in order to reduce temperature
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  27. Circadian rhythms
    • Suprachiasmatic nucleus is an endogenous pacemaker by having cells that fire in a 24-hour cycle and others that can be entrained to a 24-hour day/light cycle by input from photosensitive retinal ganglion cells
    • Projections from the suprachiasmatic nucleus extend throughout the hypothalamus and influence secretion of releasing hormones and activity in the autonomic nervous system
    • Axons from the suprachiasmatic nucleus innervate the dorsomedial hypothalamus which send axons via the hypothalamospinal pathway to innervate pre-ganglionic sympathetic neurons, which synapse in the superior cervical ganglion on post-ganglionic neurons that influence the secretion of melatonin by the pineal gland
    • Melatonin is secreted during night-time and acts on the thyroid, liver, pancreatic islets (inhibits insulin release), adrenal cortex (inhibits cortisol release), kidney and pituitary, and on neurons in the suprachiasmatic nucleus through MT1 and 2 receptors
  28. Sleep control in the hypothalamus
    • Ventrolateral preoptic nucleus (VLPO) is active during sleep and inhibits the tuberomammillary nucleus (TMN) via GABA
    • TMN projections release histamine which is released diffusely throughout the cerebral cortex and in components of the ascending reticular activating system (ARAS)
    • Therefore, histamines make us awake
    • Neurons in the lateral hypothalamus (near the fornix) are active during wakefulness, keeping the "switch" in the wake position by orexin/hypocretin peptides (??) and by exciting the TMN
  29. Narcolepsy
    • Orexin is absent from the hypothalamus, prevenging the neurons of the lateral hypothalamus from exciting the tuberomammillary nucleus (TMN), which releases histamine while awake
    • Could also be a posterior hypothalamic lesion (they also cause encephalitis lethargica)
  30. Hypothalamic control of food intake
    • Short-term signals by the GI tract (cholecystokinin and ghrelin) act on the arcuate nucleus to signal satiety
    • The pancreas and stomach release ghrelin to signal hunger; ghrelin acts on the neuropeptide Y (NPY) neurons
    • Long-term signals indicate body fat content
    • Leptin, released by adipose tissue, inhibits NPY neurons and activates POMC neurons; obese individuals can become resistant to leptin since they have constantly high levels
    • Insulin modulates the effects of ghrelin and leptin, but also acts on hypothalamic neurons that can control the glucose output of the liver
    • Monoamines can influence feeding; central norepinephrine increases feeding; serotonin decreases feeding (fenfluramine was a serotonin agonist)
    • The arcuate nucleus has NPY that promotes feeding (orexigenic) and POMC that inhibits feeding (anorexigenic); the arcuate nucleus also heavily innervates the lateral hypothalamus
  31. Lesions affecting eating
    • Lateral hypothalamus: Aphagia (abolish eating) and adipsia (abolish drinking) probably due to destruction of orexin neurons
    • Medial hypothalamus: Hyperphagia (uncontrollable eating) and uncontrollable drinking probably due to destruction of structures that inhibit feeding
  32. Hypothalamic control of salt and water intake
    • Hypovolemia: Loss of body fluid activates baroreceptors that cause release of vasopressin/ADH and initiate drinking; angiotensin II is also released from the kidney initiates vasopressin release and drinking via the circumventricular subfornical organ
    • Decreased serum osmolality: The organum vasculosum of the lamina terminalis (OVLT) senses the decrease and signals the anterior hypothalamus to increase salt appetite
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  33. Sexual behavior
    • The anterior pituitary controls development and cyclic control of reproductive function, but the precise role of the hypothalamus is poorly understood
    • Lesions of the medial hypothalamus are often associated with hypersexuality
  34. Mood
    • Aggression: Stimulation of anterolateral hypothalamus (requires medial amygdala), vasopressin, or medial hypothalamic lesions
    • Inhibition of aggression: Stimulation of the ventromedial hypothalamus (also requires medial amygdala) or serotonin
  35. Frohlich's syndrome (adiposogenital dystrophy)
    • Obesity, under-developed genitalia and small stature, and polydipsia
    • Often caused by a hypothalamic tumor
  36. Kleine-Levin syndrome
    • Hyperphagia, hypersexuality, amnesia, and hypersomnolence
    • Believed to be an inherited hypothalamic developmental disorder
  37. Kallmann's syndrome
    • Anosmia (loss of smell), hypogonadism, and delayed puberty
    • Failure of gonadotrophin-producing neurons to migrate into the hypothalamus
Card Set
Neuroscience Test 2, Hypothalamus
Flashcards over Hypothalamus I and II lectures