1. GluA1 and its PDZ-interaction: a role in experience-dependent behavioral plasticity in the forced swim test.
- Author
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Freudenberg F, Marx V, Mack V, Layer LE, Klugmann M, Seeburg PH, Sprengel R, and Celikel T
- Subjects
- Animals, Helplessness, Learned, Mice, Mice, Inbred C57BL, Promoter Regions, Genetic, Receptors, AMPA metabolism, Swimming, Behavior, Animal physiology, Hippocampus metabolism, Learning physiology, Neuronal Plasticity physiology, Neurons physiology, PDZ Domains physiology, Receptors, AMPA genetics
- 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 © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2013
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