Cell
Volume 149, Issue 5, 25 May 2012, Pages 1152-1163
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Article
Identification of the Cortical Neurons that Mediate Antidepressant Responses

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Summary

Our understanding of current treatments for depression, and the development of more specific therapies, is limited by the complexity of the circuits controlling mood and the distributed actions of antidepressants. Although the therapeutic efficacy of serotonin-specific reuptake inhibitors (SSRIs) is correlated with increases in cortical activity, the cell types crucial for their action remain unknown. Here we employ bacTRAP translational profiling to show that layer 5 corticostriatal pyramidal cells expressing p11 (S100a10) are strongly and specifically responsive to chronic antidepressant treatment. This response requires p11 and includes the specific induction of Htr4 expression. Cortex-specific deletion of p11 abolishes behavioral responses to SSRIs, but does not lead to increased depression-like behaviors. Our data identify corticostriatal projection neurons as critical for the response to antidepressants, and suggest that the regulation of serotonergic tone in this single cell type plays a pivotal role in antidepressant therapy.

Highlights

► S100a10 bacTRAP mice target a novel population of corticostriatal neurons ► S100a10 corticostriatal neurons respond specifically to chronic SSRI treatment ► Deletion of p11 abolishes the molecular responses to SSRI treatment in these cells ► Cortex-specific ablation of p11 abolishes behavioral responses to SSRI treatment

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