Synaptic alpha 5 subunit-containing GABAA receptors mediate IPSPs elicited by dendrite-preferring cells in rat neocortex.

Previous studies indicated that one class of dendrite-preferring hippocampal interneurones inhibits pyramidal cells via alpha 5 gamma-aminobutyric acid (GABA(A)) receptors whereas parvalbumin- and CCK-containing basket cells act via alpha1 and alpha2/3 GABA(A) receptors, respectively. This study asked whether there is selective insertion of different alpha subunit-containing GABA(A) receptors at neocortical inhibitory synapses innervated by specific classes of interneurones. The benzodiazepine site pharmacology of inhibitory postsynaptic potentials (IPSPs) elicited in neocortical pyramidal cells by 3 classes of interneurones was explored with dual whole-cell recordings in neocortical slices from juvenile rats (P18-23). Fast IPSPs activated by multipolar interneurones with narrow spikes and nonadapting firing patterns were powerfully enhanced by the alpha1-preferring agonist zolpidem, suggesting mediation via larger proportion of alpha1 GABA(A) receptors than those activated by multipolar, adapting interneurones, which were less strongly enhanced by zolpidem, but equally insensitive to the alpha 5-selective inverse agonist IA alpha 5 (MSD, Essex, UK) suggesting mediation predominantly via alpha2/3 GABA(A) receptors. In contrast, the IPSPs elicited by bitufted, dendrite-preferring interneurones were reduced by IA alpha 5 and by zinc and insensitive to zolpidem despite enhancement by the broad-spectrum agonist, diazepam. Thus insertion of GABA(A) receptors at synapses on neocortical pyramids is input-specific, with proximal inhibition employing alpha1 and alpha2/3 GABA(A) receptors and dendrite-preferring bitufted interneurones activating alpha 5 GABA(A) receptors.