Impaired GABAergic transmission and altered hippocampal synaptic plasticity in collybistin‐deficient mice
Identifieur interne : 000591 ( Main/Exploration ); précédent : 000590; suivant : 000592Impaired GABAergic transmission and altered hippocampal synaptic plasticity in collybistin‐deficient mice
Auteurs : Theofilos Papadopoulos [Allemagne] ; Martin Korte [Allemagne] ; Volker Eulenburg [Allemagne] ; Hisahiko Kubota [Allemagne] ; Marina Retiounskaia [Allemagne] ; Robert J. Harvey [Royaume-Uni] ; Kirsten Harvey [Royaume-Uni] ; Gregory A. O'Sullivan [Allemagne] ; Bodo Laube [Allemagne] ; Swen Hülsmann [Allemagne] ; Jörg R P. Geiger [Allemagne] ; Heinrich Betz [Allemagne]Source :
- The EMBO Journal [ 0261-4189 ] ; 2007-09-05.
Abstract
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.
Url:
DOI: 10.1038/sj.emboj.7601819
Affiliations:
- Allemagne, Royaume-Uni
- Angleterre, Basse-Saxe, District de Darmstadt, Grand Londres, Hesse (Land)
- Francfort-sur-le-Main, Göttingen, Londres
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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.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Basse-Saxe</li><li>District de Darmstadt</li><li>Grand Londres</li><li>Hesse (Land)</li></region><settlement><li>Francfort-sur-le-Main</li><li>Göttingen</li><li>Londres</li></settlement></list><tree><country name="Allemagne"><region name="Hesse (Land)"><name sortKey="Papadopoulos, Theofilos" sort="Papadopoulos, Theofilos" uniqKey="Papadopoulos T" first="Theofilos" last="Papadopoulos">Theofilos Papadopoulos</name></region><name sortKey="Betz, Heinrich" sort="Betz, Heinrich" uniqKey="Betz H" first="Heinrich" last="Betz">Heinrich Betz</name><name sortKey="Eulenburg, Volker" sort="Eulenburg, Volker" uniqKey="Eulenburg V" first="Volker" last="Eulenburg">Volker Eulenburg</name><name sortKey="Geiger, Jorg R P" sort="Geiger, Jorg R P" uniqKey="Geiger J" first="Jörg R P" last="Geiger">Jörg R P. Geiger</name><name sortKey="Hulsmann, Swen" sort="Hulsmann, Swen" uniqKey="Hulsmann S" first="Swen" last="Hülsmann">Swen Hülsmann</name><name sortKey="Korte, Martin" sort="Korte, Martin" uniqKey="Korte M" first="Martin" last="Korte">Martin Korte</name><name sortKey="Kubota, Hisahiko" sort="Kubota, Hisahiko" uniqKey="Kubota H" first="Hisahiko" last="Kubota">Hisahiko Kubota</name><name sortKey="Kubota, Hisahiko" sort="Kubota, Hisahiko" uniqKey="Kubota H" first="Hisahiko" last="Kubota">Hisahiko Kubota</name><name sortKey="Laube, Bodo" sort="Laube, Bodo" uniqKey="Laube B" first="Bodo" last="Laube">Bodo Laube</name><name sortKey="O Sullivan, Gregory A" sort="O Sullivan, Gregory A" uniqKey="O Sullivan G" first="Gregory A" last="O'Sullivan">Gregory A. O'Sullivan</name><name sortKey="Retiounskaia, Marina" sort="Retiounskaia, Marina" uniqKey="Retiounskaia M" first="Marina" last="Retiounskaia">Marina Retiounskaia</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Harvey, Robert J" sort="Harvey, Robert J" uniqKey="Harvey R" first="Robert J" last="Harvey">Robert J. Harvey</name></region><name sortKey="Harvey, Kirsten" sort="Harvey, Kirsten" uniqKey="Harvey K" first="Kirsten" last="Harvey">Kirsten Harvey</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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