Laboratory of Molecular Biology, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Ave., New York, NY 10065, USA.
Cell. 2012 May 25;149(5):1152-63. doi: 10.1016/j.cell.2012.03.038.
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.
我们对当前抑郁症治疗方法的理解，以及更具针对性疗法的发展，受到控制情绪的回路复杂性和抗抑郁药物分布作用的限制。尽管特定的血清素再摄取抑制剂（SSRIs）的治疗效果与皮质活动的增加相关，但对于其作用至关重要的细胞类型仍不清楚。在这里，我们采用 bacTRAP 翻译谱分析表明，表达 p11（S100a10）的第 5 层皮质纹状体锥体神经元对慢性抗抑郁治疗有强烈而特异的反应。这种反应需要 p11，并且包括 Htr4 表达的特异性诱导。皮质特异性缺失 p11 会消除 SSRIs 的行为反应，但不会导致抑郁样行为增加。我们的数据表明，皮质纹状体投射神经元对抗抑郁药的反应至关重要，并表明该单一细胞类型中 5-羟色胺能张力的调节在抗抑郁治疗中起着关键作用。
