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

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 postsynapt...

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Published in:The EMBO journal 2007-09, Vol.26 (17), p.3888-3899
Main Authors: Papadopoulos, Theofilos, Korte, Martin, Eulenburg, Volker, Kubota, Hisahiko, Retiounskaia, Marina, Harvey, Robert J, Harvey, Kirsten, O'Sullivan, Gregory A, Laube, Bodo, Hülsmann, Swen, Geiger, Jörg R P, Betz, Heinrich
Format: Article
Language:English
Subjects:
Amygdala - physiology
Animals
Carrier Proteins - physiology
Cellular biology
GABAA receptor
GEF
gephyrin
glycine receptor
Guanine Nucleotide Exchange Factors - genetics
Guanine Nucleotide Exchange Factors - physiology
Hippocampus - physiology
Long-Term Potentiation
Long-Term Synaptic Depression
Maze Learning
Membrane Proteins - physiology
Mental depression
Mice
Mice, Knockout
Molecular biology
Motor Activity
Neuronal Plasticity
Neurotransmitters
Patch-Clamp Techniques
Plasticity
Presynaptic Terminals - physiology
Receptors, GABA-A - physiology
Receptors, Glycine - metabolism
Rho Guanine Nucleotide Exchange Factors
spatial memory
Synapses - physiology
Synaptic Transmission
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Summary: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.
ISSN:0261-4189
1460-2075
DOI:10.1038/sj.emboj.7601819