Back to Search
Start Over
GluA1 and its PDZ-interaction: A role in experience-dependent behavioral plasticity in the forced swim test
- Source :
-
Neurobiology of Disease . Apr2013, Vol. 52, p160-167. 8p. - Publication Year :
- 2013
-
Abstract
- 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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 09699961
- Volume :
- 52
- Database :
- Academic Search Index
- Journal :
- Neurobiology of Disease
- Publication Type :
- Academic Journal
- Accession number :
- 85426261
- Full Text :
- https://doi.org/10.1016/j.nbd.2012.12.003