Activity-Dependent Regulation of GABAA Receptors

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GABAA 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 γ-aminobutyric acid (GABAA) receptor subtypes. Activity-dependent mechanisms nevertheless modulate on a short-term basis the cell surface expression of GABAA 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 GABAA 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 GABAA receptor subtypes, suggesting that additional factors are involved.

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