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

• DOI: 10.1038/sj.emboj.7601819
• Publication Date: 2007-08-09T12:48:06Z
• Authors: Theofilos Papadop...; Martin Korte; Volker Eulenburg; Hisahiko Kubota; Marina Retiounskaia; Robert J Harvey; Kirsten Harvey; Gregory A O'Sullivan; Bodo Laube; Swen Hülsmann; Jörg R P Geiger; Heinrich Betz
• Keywords: 571; Patch-Clamp Techniques; FoR 11 (Medical and Health Sciences); Long-Term Potentiation; Presynaptic Terminals; Motor Activity; Hippocampus; Synaptic Transmission; Mice; 03 medical and health sciences; Receptors, Glycine; Animals; Guanine Nucleotide Exchange Factors; GEF; Maze Learning; FoR 06 (Biological Sciences); long-term potentiation; Mice, Knockout; ddc:610; 0303 health sciences; Neuronal Plasticity; Long-Term Synaptic Depression; Membrane Proteins; GABAA Receptor; spatial memory; Amygdala; Receptors, GABA-A; gephyrin; FoR 08 (Information and Computing Sciences); Synapses; glycine receptor; Carrier Proteins; Rho Guanine Nucleotide Exchange Factors

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.