Behavioral Neuroscience, lecture on GABA
BIOLOGICAL RHYTHMS
VIII. g-aminobutyric Acid (GABA)
A. NH2-CH2-CH2-CH2-COOH
1. formed from Glu by L-glutamic acid decarboxylase (GAD)
a. GABA shunt: bypass from Kreb's to provide glutamate
b. GABA catabolized by GABA-T
(GABA transaminase = a-ketoglutarate aminotransferase)
i. NH3 to glutamate synthesis
2. inhibitory amino acid transmitter = inhibits firing of neurons
B. Receptors - 2 major types
1. GABAA = ligand-gated Cl- channel
a. postsynaptic inhibition: hyperpolarizing
postsynaptic membrane
i. influx of Cl-
b. GABAA on GABA neurons is functionally
presynaptic inhibition
c. 5 subunits - 2a + 2b + 1g (usually)
i. a binds benzodiazepines (valium)
ii. b binds GABA
iii. other sites near membrane bind barbiturates, anesthetics,
alcohols and H2O, neuroactive steroids; and
inside bind convulsants and picrotoxin
iv. extraordinary structural diversity: a1-6, b1-4, g1-3, d, e, q, r1-2
(1) yields functional diversity
v. superfamily of ligand gated channels including
nicotinic, 5-HT3, NMDA, AMPA, KA & glycine-R
b. GABAB (fewer)
i. often presynaptic
(1)G K+ ® open K+ or close Ca++ channels
(a) autoreceptors inhibit GABA neurons
by hyperpolarization
(2) also Gi® X AC
ii. sometimes postsynaptic
(1) phospholipase A2 ® cAMP
c. GABAC in retina
i. more sensitive Cl- channel
d. GABA transporter (GABAT)
C. GABA GHT projections, IGL to SCN shell neurons colocalize NPY
1. GABA interneurons in SCN core (with VIP/GRP)
and shell (with AVP/calretinin)
a. intrinsic neurons in cortex, hippocampus, cerebellum,
olfactory bulb and retina...
2. projections from hypothalamus to cerebral cortex
a. direct pathway for limbic, emotional, and visceral
information to reach the cortex
3. projections of striatum to substantia nigra