Biologic substrate part 2 Jeff Clothier, M.D.

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.

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

location hypothalamus Pituitary Corpus callosum Anterior cingulate thalamus

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

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

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

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

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

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)

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

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

Anatomic sketch Amygdala hippocampus Cingulate gyrus Parahippocampal gyrus fornix Septa l area Mamillary bodies thalamu s Orbitofrontal cortex n. accumbens Cortical influences

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

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

Dexamethasone suppression test Pathologic response is nonsuppression. nonspecific

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

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?

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

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

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