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

• Published in: The EMBO journal Vol. 26; no. 17; pp. 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: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 05-09-2007; Blackwell Publishing Ltd; Nature Publishing Group
• 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
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/sj.emboj.7601819

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.