GABA
A receptor heterogeneity is based on the combinatorial assembly
of a large family of subunits into distinct receptor subtypes.
A neuron-specific expression pattern of receptor subtypes has
been demonstrated in adult rat brain, which can be reproduced
in vitro in primary neuron cultures. This suggests that genetic
programs established during ontogeny govern the expression of
-aminobutyric acid (GABA
A) receptor subtypes. Activity-dependent
mechanisms nevertheless modulate on a short-term basis the cell
surface expression of GABA
A receptors, as demonstrated in cultured
hippocampal neurons upon blockade of synaptic transmission or
application of brain-derived neurotrophic factor. Preliminary
evidence points to changes in protein phosphorylation as a mechanism
underlying short-term activity-dependent regulation of GABA
A receptors.
In vivo, chronic pharmacological modulation of neuronal
activity during development, while having marked effects on
the rate of cortical growth, failed to influence the expression
of GABA
A receptor subtypes, suggesting that additional factors
are involved.
