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          Institute: MPI für medizinische Forschung     Collection: Jahbruch 2014_archival     Display Documents



ID: 681476.0, MPI für medizinische Forschung / Jahbruch 2014_archival
GluA1 and its PDZ−interaction: a role in experience−dependent behavioral plasticity in the forced swim test
Translation of Title:GluA1 and its PDZ−interaction: a role in experience−dependent behavioral plasticity in the forced swim test
Authors:Freudenberg, Florian; Marx, Verena; Mack, Volker; Layer, Liliana; Klugmann, Matthias; Seeburg, Peter H.; Sprengel, Rolf; Celikel, Tansu
Language:English
Date of Publication (YYYY-MM-DD):2013-04-01
Title of Journal:Neurobiology of Disease
Journal Abbrev.:Neurobiology of Disease
Volume:52
Start Page:160
End Page:167
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Glutamate receptor dependent synaptic plasticity plays an important role in the pathophysiology of depression. Hippocampal samples from clinically depressed patients display reduced mRNA levels for GluA1, a major subunit of AMPA receptors. Moreover, activation and synaptic incorporation of GluA1−containing AMPA receptors are required for the antidepressant−like effects of NMDA receptor antagonists. These findings argue that GluA1−dependent synaptic plasticity might be critically involved in the expression of depression. Using an animal model of depression, we demonstrate that global or hippocampus−selective deletion of GluA1 impairs expression of experience−dependent behavioral despair. This impairment is mediated by the interaction of GluA1 with PDZ−binding domain proteins, as deletion of the C−terminal leucine alone is sufficient to replicate the behavioral phenotype. Our results provide evidence for a significant role of hippocampal GluA1−containing AMPA receptors and their PDZ−interaction in experience−dependent expression of behavioral despair and link mechanisms of hippocampal synaptic plasticity with behavioral expression of depression
Free Keywords:Mouse;
Gria1;
GluR1;
GluR−A;
PDZ;
AMPA receptors;
Porsolt swim test;
Behavioral despair;
Depression
External Publication Status:published
Document Type:Article
Communicated by:wkaiser
Affiliations:MPI für medizinische Forschung/Abteilung Zellphysiologie
MPI für medizinische Forschung/Abteilung Molekulare Neurobiologie
MPI für medizinische Forschung/Abteilung Zellphysiologie/Olfaction Web
MPI für medizinische Forschung/Abteilung Molekulare Neurobiologie/Gruppe Rolf Sprengel
Identifiers:LOCALID:7885
URI:http%3A%2F%2Fpdn.sciencedirect.com%2Fscience%3F_ob...
URI:http%3A%2F%2Fdx.doi.org%2F10.1016%2Fj.nbd.2012.12....
URI:http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F23262...
DOI:10.1016%2Fj.nbd.2012.12.003
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