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  GluA1 and its PDZ-interaction: A role in experience-dependent behavioral plasticity in the forced swim test

Freudenberg, F., Marx, V., Mack, V., Layer, L., Klugmann, M., Seeburg, P. H., et al. (2013). GluA1 and its PDZ-interaction: A role in experience-dependent behavioral plasticity in the forced swim test. Neurobiology of Disease, 52, 160-167. doi:10.1016/j.nbd.2012.12.003.

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Genre: Journal Article
Alternative Title : GluA1 and its PDZ−interaction: A role in experience−dependent behavioral plasticity in the forced swim test

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NeurobiolDis_52_2013_160.pdf (Any fulltext), 704KB
 
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 Creators:
Freudenberg, Florian1, Author           
Marx, Verena1, Author           
Mack, Volker1, Author           
Layer, Liliana1, Author           
Klugmann, Matthias, Author
Seeburg, Peter H.1, Author           
Sprengel, Rolf1, Author           
Celikel, Tansu2, Author           
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1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              
2Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497701              

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Free keywords: Mouse; Gria1; GluR1; GluR−A; PDZ; AMPA receptors; Porsolt swim test; Behavioral despair; Depression
 Abstract: 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

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Language(s): eng - English
 Dates: 2012-07-212012-12-082012-12-202013-04-01
 Publication Status: Issued
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 Rev. Type: Peer
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Title: Neurobiology of Disease
  Other : Neurobiol. Dis.
Source Genre: Journal
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Publ. Info: Oxford : Academic Press
Pages: - Volume / Issue: 52 Sequence Number: - Start / End Page: 160 - 167 Identifier: ISSN: 0969-9961
CoNE: https://pure.mpg.de/cone/journals/resource/954922649144