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Understanding the Biologic Substrate: Hypothalamus, Limbic System, and Neuroendocrine Testing

Explore the functions of the hypothalamus, components of the limbic system, and neuroendocrine influences on behavior. Learn about reward and reinforcement systems, neuroendocrine tests, and more.

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Understanding the Biologic Substrate: Hypothalamus, Limbic System, and Neuroendocrine Testing

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  1. Biologic substrate part 2 Jeff Clothier, M.D.

  2. Objectives • describe the three functions of the hypothalamus • describe major components of the limbic system • describe the role of peptide neurotransmitters on behavior • describe the neuroendocrine influences on behavior • describe the common neuroendocrine tests used in studying abnormal behavior • compare and contrast the effects of irritative and destructive lesions on the ventromedial, lateral, anterior and posterior hypothalumas. • to describe the major components of the reward and reinforcement system as described in the syllabus.

  3. Three functions of the hypothalamus • Control of autonomic funtions • Control of neuroendocrine systems • integration of drives and emotions with homeostatic needs

  4. Corpus callosum thalamus Anterior cingulate hypothalamus Pituitary location

  5. Mamillothalamic tract Fornix Mamillary region supraoptic region Infundibulum Tuberal region Pituitary Closer look

  6. Hypothalamus-regional considerations Supraoptic region • preoptic, paraventricular anterior, suprachiasmatic, and supraoptic nuclie • Circumventricular organs- no BBB • monitors and is influenced by internal milieu • adjusts vegative functions to meet homeostatic needs

  7. Hypothalamic-regional considerations Tuberal region • Just above infundibulum • dorsomedial, ventromedial, lateral, rostral posterior, acruate, and median eminence • Median Forebrain bundle comes through this region • important for reward and reinforcement (hedonic drives) • “stim the lat get fat, stim the ven get thin” • destructive has opposite effect of irritative

  8. Control of the adenohypophysis mamillothalamic tract- important in memory Releasing and inhibiting factors TRF/TRH GRF/GRH GHRF/somatotropin CRF/CRH Hypothalamic regional considerations- Mamillary region • somatostatin • PIF (dopamine) • Vasopressin • Oxytocin

  9. Autonomic nervous system functions of the hypothalamus • Anterior/posterior gradient Anterior-Parasympathetic activation Medial/posterior- Sympathetic activation

  10. Biology of monogamy as a complex behavior • Neuropeptides influence the pituitary but also have more distant effects within the CNS • Prairie vole • Male bonding-vasopressin (peaks during sexual arousal) • Female bonding- oxcytocin (peaks during orgasm and child birth and lactation)

  11. Limbic system • Functions at the boundary of cognition and motor activity • Individualized to a degree by experience by memory

  12. relation of reward and reinforcement and motor systems • Nigrostriatal- • SN to caudate and putamen. • Uses dopamine • Mesolimbic • VTA to n. accumbens and aygdala • SN----------VTA • Caudate---n accumbens • Caudate---amygdala

  13. fornix Cingulate gyrus Septal area thalamus Mamillary bodies Orbitofrontal cortex n. accumbens Parahippocampal gyrus hippocampus Amygdala Cortical influences Anatomic sketch

  14. Limbic system • Role in memory • Role in reward and reinforcement • Role in emotion and motivation especially in the orbitomedial frontal region. • Bilateral relationship with the hypothalamus. Recall the prairie vole

  15. Neuroendocrine testing in psychiatry • Window in the brain • HPA axis • with stress • increased cortisol secretion at baseline

  16. Dexamethasone suppression test • Pathologic response is nonsuppression. nonspecific

  17. TRH stimulation test • Give TRH and follow TSH production • Norepinephrine usually causes release of TRH • depression is associated with a blunted response to TRH. Normalizes with remission of illness • Also not highly sensitive or specific

  18. Growth hormone • GH is released at peaks through day and during first slow wave sleep period • Hypoglycemia stimulates GH release • influenced by central NE • insulin and clonidine normally stimulate GH release • Depression the response is blunted • ? Subsensitivity of alpha 2 receptors in depression?

  19. Summary of neuroendocrine testing in depressive illness • DST- nonsuppression • Blunted TSH release with TRH stimulation • Blunted GH release with clonidine or insulin • All are not very specific and sensitive • not useful clinically

  20. Prolactin • Release is normally inhibited by Dopamine • Antipsychotic drugs block dopamine • causes increased prolactin • galactorrhea

  21. Reward and reinforcement • Heart of system is the median forebrain bundle • catecholamine fibers from midbrain to anterior septal area • important role for dopamine and norepinephrine • Intracranial self stimulation model • importance of MFB, Septal area, N accumbens, ventral tegmental area, lateral HT • libido and substance addictions • Depression and Parkinson’s

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