Synaptic α5 Subunit–Containing GABAA Receptors Mediate IPSPs Elicited by Dendrite-Preferring Cells in Rat Neocortex

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Previous studies indicated that one class of dendrite-preferring hippocampal interneurones inhibits pyramidal cells via α5 γ-aminobutyric acid (GABAA) receptors whereas parvalbumin- and CCK-containing basket cells act via α1 and α2/3 GABAA receptors, respectively. This study asked whether there is selective insertion of different α subunit–containing GABAA 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 α1-preferring agonist zolpidem, suggesting mediation via larger proportion of α1 GABAA receptors than those activated by multipolar, adapting interneurones, which were less strongly enhanced by zolpidem, but equally insensitive to the α5-selective inverse agonist IAalpha5 (MSD, Essex, UK) suggesting mediation predominantly via α2/3 GABAA 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 GABAA receptors at synapses on neocortical pyramids is input-specific, with proximal inhibition employing α1 and α2/3 GABAA receptors and dendrite-preferring bitufted interneurones activating α5 GABAA receptors.

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