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