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Cerebral Cortex Advance Access originally published online on October 19, 2007
Cerebral Cortex 2008 18(6):1260-1271; doi:10.1093/cercor/bhm160
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© 2007 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Synaptic {alpha}5 Subunit–Containing GABAA Receptors Mediate IPSPs Elicited by Dendrite-Preferring Cells in Rat Neocortex

Afia B. Ali and Alex M. Thomson

Department of Pharmacology, School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK

Address correspondence to email: afia.ali{at}pharmacy.ac.uk.

Previous studies indicated that one class of dendrite-preferring hippocampal interneurones inhibits pyramidal cells via {alpha}5 {gamma}-aminobutyric acid (GABAA) receptors whereas parvalbumin- and CCK-containing basket cells act via {alpha}1 and {alpha}2/3 GABAA receptors, respectively. This study asked whether there is selective insertion of different {alpha} 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 {alpha}1-preferring agonist zolpidem, suggesting mediation via larger proportion of {alpha}1 GABAA 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 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 {alpha}1 and {alpha}2/3 GABAA receptors and dendrite-preferring bitufted interneurones activating {alpha}5 GABAA receptors.

Key Words: benzodiazepine site • GABAA • interneuron • IPSPs • neocortex • synaptic


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