Cholinergic interneurons in the nucleus accumbens regulate depression-like behavior
Cholinergic interneurons in the nucleus accumbens regulate depression-like behavior
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DOI：
10.1073/pnas.1209293109
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发表时间：
2012-07-10
影响因子：
11.1
通讯作者：
Greengard, Paul
中科院分区：
文献类型：
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作者：
Warner-Schmidt, Jennifer L.;Schmidt, Eric F.;Greengard, Paul
大量的研究表明，神经核（NAC）是控制奖励反应，动机和情绪的神经回路中的关键部位，但这些过程背后的神经元细胞类型尚不清楚。识别调节抑郁样状态的神经元细胞类型将指导我们理解情绪的生物学基础及其通过重度抑郁症等疾病的调节。利用最近的研究结果表明，theserotonin受体伴侣，p11，是一个重要的抑郁样状态的分子调节器，在这里，我们确定胆碱能中间神经元（CINs）作为p11在NAC的主要作用部位。小鼠在NACCINs中p11水平降低后观察到抑郁样行为。这种表型通过沉默这些细胞中的神经元传递来重现，表明多巴胺胆碱能神经元活性调节抑郁样行为，并表明多巴胺CIN活性对情绪和动机的调节至关重要。
A large number of studies have demonstrated that the nucleus accumbens (NAC) is a critical site in the neuronal circuits controlling reward responses, motivation, and mood, but the neuronal cell type(s) underlying these processes are not yet known. Identification of the neuronal cell types that regulate depression-like states will guide us in understanding the biological basis of mood and its regulation by diseases like major depressive disorder. Taking advantage of recent findings demonstrating that theserotonin receptor chaperone, p11, is an important molecular regulator of depression-like states, here we identify cholinergic interneurons (CINs) as a primary site of action for p11 in the NAC. Depression-like behavior is observed in mice after decrease of p11 levels in NAC CINs. This phenotype is recapitulated by silencing neuronal transmission in these cells, demonstrating that accumbal cholinergic neuronal activity regulates depression-like behaviors and suggesting that accumbal CIN activity is crucial for the regulation of mood and motivation.