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

T Papadopoulos; M Korte; V Eulenburg; H Kubota; M Retiounskaia; Robert J Harvey; K Harvey; G A O'Sullivan; B Laube; S Hülsmann; J R P Geiger; H Betz

doi:10.1038/sj.emboj.7601819

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

Journal article

Peer reviewed

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

T Papadopoulos, M Korte, V Eulenburg, H Kubota, M Retiounskaia, Robert J Harvey, K Harvey, G A O'Sullivan, B Laube, S Hülsmann, …

EMBO Journal, Vol.26(17), pp.3888-3899

2007

DOI: https://doi.org/10.1038/sj.emboj.7601819

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Abstract

GABAA Receptor

gephyrin

glycine receptor

GEF

long-term potentiation

spatial memory

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. © 2007 European Molecular Biology Organization | All Rights Reserved.

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Title: Impaired GABAergic transmission and altered hippocampal synaptic plasticity in collybistin-deficient mice
Authors: T Papadopoulos (Author) - Max-Planck-Institute for Brain Research, Germany
M Korte (Author) - Technical University Braunschweig, Germany
V Eulenburg (Author) - Max-Planck-Institute for Brain Research, Germany
H Kubota (Author) - Max-Planck-Institute for Brain Research, Germany
M Retiounskaia (Author) - Max-Planck-Institute for Brain Research, Germany
Robert J Harvey (Author) - School of Pharmacy, United Kingdom
K Harvey (Author) - School of Pharmacy, United Kingdom
G A O'Sullivan (Author) - Max-Planck-Institute for Brain Research, Germany
B Laube (Author) - Max-Planck-Institute for Brain Research, Germany
S Hülsmann (Author) - University of Göttingen, Germany
J R P Geiger (Author) - Max-Planck-Institute for Brain Research, Germany
H Betz (Author) - Max-Planck-Institute for Brain Research, Germany
Publication details: EMBO Journal, Vol.26(17), pp.3888-3899
Publisher: Wiley-Blackwell Publishing Ltd.
Date published: 2007
DOI: 10.1038/sj.emboj.7601819
ISSN: 0261-4189
Organisation Unit: School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99450568602621
Output Type: Journal article

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Web Of Science research areas: Biochemistry & Molecular Biology; Cell Biology

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