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Impaired GABAergic transmission and altered hippocampal synaptic plasticity in collybistin-deficient mice.

Papadopoulos, Theofilos and Korte, Martin and Eulenburg, Volker and Kubota, Hisahiko and Retiounskaia, Marina and Harvey, Robert J. and Harvey, Kirsten and O'Sullivan, Gregory A. and Laube, Bodo and Hülsmann, Swen and Geiger, Jörg R. P. and Betz, Heinrich (2007):
Impaired GABAergic transmission and altered hippocampal synaptic plasticity in collybistin-deficient mice.
26, In: The EMBO journal, (17), pp. 3888-99, ISSN 0261-4189, [Article]

Abstract

Collybistin (Cb) is a brain-specific guanine nucleotide exchange factor that has been implicated in plasma membrane targeting of the postsynaptic scaffolding protein gephyrin found at glycinergic and GABAergic synapses. Here we show that Cb-deficient mice display a region-specific loss of postsynaptic gephyrin and GABA(A) receptor clusters in the hippocampus and the basolateral amygdala. Cb deficiency is accompanied by significant changes in hippocampal synaptic plasticity, due to reduced dendritic GABAergic inhibition. Long-term potentiation is enhanced, and long-term depression reduced, in Cb-deficient hippocampal slices. Consistent with the anatomical and electrophysiological findings, the animals show increased levels of anxiety and impaired spatial learning. Together, our data indicate that Cb is essential for gephyrin-dependent clustering of a specific set of GABA(A) receptors, but not required for glycine receptor postsynaptic localization.

Item Type: Article
Erschienen: 2007
Creators: Papadopoulos, Theofilos and Korte, Martin and Eulenburg, Volker and Kubota, Hisahiko and Retiounskaia, Marina and Harvey, Robert J. and Harvey, Kirsten and O'Sullivan, Gregory A. and Laube, Bodo and Hülsmann, Swen and Geiger, Jörg R. P. and Betz, Heinrich
Title: Impaired GABAergic transmission and altered hippocampal synaptic plasticity in collybistin-deficient mice.
Language: English
Abstract:

Collybistin (Cb) is a brain-specific guanine nucleotide exchange factor that has been implicated in plasma membrane targeting of the postsynaptic scaffolding protein gephyrin found at glycinergic and GABAergic synapses. Here we show that Cb-deficient mice display a region-specific loss of postsynaptic gephyrin and GABA(A) receptor clusters in the hippocampus and the basolateral amygdala. Cb deficiency is accompanied by significant changes in hippocampal synaptic plasticity, due to reduced dendritic GABAergic inhibition. Long-term potentiation is enhanced, and long-term depression reduced, in Cb-deficient hippocampal slices. Consistent with the anatomical and electrophysiological findings, the animals show increased levels of anxiety and impaired spatial learning. Together, our data indicate that Cb is essential for gephyrin-dependent clustering of a specific set of GABA(A) receptors, but not required for glycine receptor postsynaptic localization.

Journal or Publication Title: The EMBO journal
Volume: 26
Number: 17
Divisions: 10 Department of Biology
10 Department of Biology > Neurophysiology and Neurosensory Systems
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Date Deposited: 11 Apr 2011 09:24
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