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

Septal area

Mamillary bodies

thalamus

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

Pituitary ACTH

adrenalcortex

Steroids

Cerebral cortex

Hippocampus

Hypothalamus CRF

Dexamethasone suppression test

Pathologic response is nonsuppression. nonspecific

Plasma cortisollevel inmicrograms/100ml

5

normalresponse"suppression"

abnormal response"nonsuppression"

11pm

30

time 8am

1 mg of dexamethasone is given PO at 11pmplasma cortisol is measured at 11pm and 8am

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