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| Subject Categories: Neuroscience |
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| The EMBO Journal
(2007) 26, 3888–3899, doi:10.1038/sj.emboj.7601819 Published online 9 August 2007 |
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| Impaired GABAergic transmission and altered hippocampal synaptic plasticity in collybistin-deficient mice |
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| Theofilos Papadopoulos1, Martin Korte2, Volker Eulenburg1, Hisahiko Kubota1, 3, Marina Retiounskaia1, Robert J Harvey4, Kirsten Harvey4, Gregory A O'Sullivan1, Bodo Laube1, Swen Hülsmann5, Jörg R P Geiger3 and Heinrich Betz1 |
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1 Department of Neurochemistry, Max-Planck-Institute for Brain Research, Frankfurt, Germany 2 Zoological Institute, Technical University Braunschweig, Braunschweig, Germany 3 Independent Hertie Research Group, Max-Planck-Institute for Brain Research, Frankfurt, Germany 4 Department of Pharmacology, The School of Pharmacy, London, UK 5 Department of Neuro- and Sensory Physiology, University of Göttingen, Göttingen, Germany To whom correspondence should be addressed Heinrich Betz, Department of Neurochemistry, Max-Planck-Institute for Brain Research, Deutschordenstrassee 46, 60528 Frankfurt am Main, Germany. Tel.: +49 69 96769 220; Fax: +49 69 96769 441; E-mail: neurochemie@mpih-frankfurt.mpg.de Received 23 March 2007; Accepted 19 July 2007; Published online 9 August 2007. |
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| Abstract |
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| 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 GABAA 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 GABAA receptors, but not required for glycine receptor postsynaptic localization. |
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| Keywords: GABAA receptor, gephyrin, glycine receptor, GEF, long-term potentiation, spatial memory |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSGephyrin, a major player in GABAergic postsynaptic membrane assembly? Nature Neuroscience News and Views (01 Nov 1998) Building inhibitory synapses: exchange factors getting into the act? Nature Neuroscience News and Views (01 Jan 2000) RESEARCHThe EMBO Journal Article Developmental switch from GABA to glycine release in single central synaptic terminals Nature Neuroscience Article (01 Jan 2004) |
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