| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 6022374 | Neurobiology of Disease | 2013 | 8 Pages |
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.
► Experience-dependent expression of behavioral despair is GluA1-dependent. ► Hippocampus-specific removal of GluA1 impairs expression of behavioral despair. ► GluA1 PDZ-interaction is required for the expression of behavioral despair.
