| First Author | Freudenberg F | Year | 2013 |
| Journal | Neurobiol Dis | Volume | 52 |
| Pages | 160-7 | PubMed ID | 23262314 |
| Mgi Jnum | J:197650 | Mgi Id | MGI:5494221 |
| Doi | 10.1016/j.nbd.2012.12.003 | Citation | Freudenberg F, et al. (2013) GluA1 and its PDZ-interaction: a role in experience-dependent behavioral plasticity in the forced swim test. Neurobiol Dis 52:160-7 |
| abstractText | 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. |
