Evidence that GABA_A Receptor Subunit mRNA Expression During Development Is Regulated by GABA_A Receptor Stimulation

Abstract

The expression of six mRNA species (α2, α3, α5, β2, β3, and γ2) encoding for GABAA receptor subunits was followed in cultured early postnatal cortical neurons by in situ hybridization histochemistry. In untreated control cultures it was found that these subunit mRNA expression profiles closely follow those seen during development in vivo. α3, α5, and β3 subunit expression declined, α2 expression increased, whereas β2 and γ2 subunit mRNA expression remained relatively constant. To test the hypothesis that GABAA receptor stimulation regulates these expression profiles, we tested the effect of a GABAA receptor positive modulator, allopregnanolone, and a GABAA receptor noncompetitive antagonist, tert‐butylbicyclophosphorothionate (TBPS). It was found that allopregnanolone augmented the rate at which the α3, α5, or β3 subunit mRNA expression declined and prevented the increase in α2 subunit mRNA expression. As well, allopregnanolone down‐regulated β2 subunit mRNA expression. TBPS, on the other hand, up‐regulated α3, α5, β2, and β3 subunit mRNA expression. It also down‐regulated the expression of α2 subunit mRNA. Both allopregnanolone and TBPS had no effect on γ2 subunit mRNA expression. These results imply that the developmental switchover of GABA receptor subunit mRNA expression is regulated by GABAA receptor activity.

Egr3 stimulation of GABRA4 promoter activity as a mechanism for seizure-induced up-regulation of GABA A receptor α4 subunit expression

“…A variety of evidence suggests that GABRs vary their rates of transcription in response to extracellular signals (19)(20)(21)(22). In this study, we used stimulation of PKC in primary cultured hippocampal neurons (HNs) to increase levels of GABRA4 transcripts, mirroring changes shown in several epilepsy models (6)(7)(8).…”

GABA Induces Activity Dependent Delayed-onset Uncoupling of GABA/Benzodiazepine Site Interactions in Neocortical Neurons

“…DISCUSSION GABA A R activation-dependent plasticity of GABAergic synapses has been described both in neonatal and adult brain and has been suggested to play a role in the development and function of neuronal networks (29 -31). Evidence that GABA A R activation alters GABA A R subunit gene expression also comes from studies of neurons in culture (20,21) and cultures treated with the GABA A R positive endogenous modulator allopregnanolone at different stages of development (32).…”

Neurosteroid regulation of central nervous system development

“…GABA A receptor stimulation also regulates expression of GABA A receptor subunits (Poulter et al, 1997). Expression of GABA A subunits in cultured cortical neurons paralleled their expression in vivo.…”