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Fast and slow inhibition in the visual thalamus is influenced by allocating GABAA receptors with different gamma subunits

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Title: Fast and slow inhibition in the visual thalamus is influenced by allocating GABAA receptors with different gamma subunits
Authors: Brickley, SG
Ye, Z
Yu, X
Houston, C
Aboukhalil, Z
Franks, N
Wisden, W
Item Type: Journal Article
Abstract: Cell-type specific differences in the kinetics of inhibitory postsynaptic conductance changes (IPSCs) are believed to impact upon network dynamics throughout the brain. Much attention has focused on how GABAA receptor (GABAAR) α and β subunit diversity will influence IPSC kinetics, but less is known about the influence of the γ subunit. We have examined whether GABAAR γ subunit heterogeneity influences IPSC properties in the thalamus. The γ2 subunit gene was deleted from GABAARs selectively in the dorsal lateral geniculate nucleus (dLGN). The removal of the γ2 subunit from the dLGN reduced the overall spontaneous IPSC (sIPSC) frequency across all relay cells and produced an absence of IPSCs in a subset of relay neurons. The remaining slower IPSCs were both insensitive to diazepam and zinc indicating the absence of the γ2 subunit. Because these slower IPSCs were potentiated by methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), we propose these IPSCs involve γ1 subunit-containing GABAAR activation. Therefore, γ subunit heterogeneity appears to influence the kinetics of GABAAR-mediated synaptic transmission in the visual thalamus in a cell-selective manner. We suggest that activation of γ1 subunit-containing GABAARs give rise to slower IPSCs in general, while faster IPSCs tend to be mediated by γ2 subunit-containing GABAARs.
Issue Date: 4-Apr-2017
Date of Acceptance: 20-Mar-2017
URI: http://hdl.handle.net/10044/1/45749
DOI: https://dx.doi.org/10.3389/fncel.2017.00095
ISSN: 1662-5102
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Cellular Neuroscience
Volume: 11
Copyright Statement: © 2017 Ye, Yu, Houston, Aboukhalil, Franks, Wisden and Brickley. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms (https://creativecommons.org/licenses/by/4.0/)
Sponsor/Funder: Medical Research Council (MRC)
Wellcome Trust
Biotechnology and Biological Sciences Research Council (BBSRC)
Wellcome Trust
Wellcome Trust
Wellcome Trust
Netherlands Organisation for Scientific Research
Funder's Grant Number: G0901892
Keywords: GABA
Publication Status: Published
Article Number: 95
Appears in Collections:Faculty of Natural Sciences