Synaptic α5 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 alpha 1 and alpha 2/3 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 alpha 1-preferring agonist zolpidem, suggesting mediation via larger proportion of alpha 1 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 IAalpha5 (MSD, Essex, UK) suggesting mediation predominantly via alpha 2/3 GABA(A) receptors. In contrast, the IPSPs elicited by bitufted, dendrite-preferring interneurones were reduced by IAalpha5 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 alpha 1 and alpha 2/3 GABA(A) receptors and dendrite-preferring bitufted interneurones activating alpha 5 GABA(A) receptors.