Virk Michael S, Sagi Yotam, Medrihan Lucian, Leung Jenny, Kaplitt Michael G, Greengard Paul
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065; Department of Neurosurgery, Weill Cornell Medical Center, New York, NY 10065;
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065;
Proc Natl Acad Sci U S A. 2016 Jan 19;113(3):734-9. doi: 10.1073/pnas.1524183113. Epub 2016 Jan 5.
Little is known about the molecular similarities and differences between neurons in the ventral (vSt) and dorsal striatum (dSt) and their physiological implications. In the vSt, serotonin [5-Hydroxytryptamine (5-HT)] modulates mood control and pleasure response, whereas in the dSt, 5-HT regulates motor behavior. Here we show that, in mice, 5-HT depolarizes cholinergic interneurons (ChIs) of the dSt whereas hyperpolarizing ChIs from the vSt by acting on different 5-HT receptor isoforms. In the vSt, 5-HT1A (a postsynaptic receptor) and 5-HT1B (a presynaptic receptor) are highly expressed, and synergistically inhibit the excitability of ChIs. The inhibitory modulation by 5-HT1B, but not that by 5-HT1A, is mediated by p11, a protein associated with major depressive disorder. Specific deletion of 5-HT1B from cholinergic neurons results in impaired inhibition of ACh release in the vSt and in anhedonic-like behavior.
关于腹侧纹状体（vSt）和背侧纹状体（dSt）中神经元之间的分子异同及其生理意义，我们所知甚少。在腹侧纹状体中，血清素[5-羟色胺（5-HT）]调节情绪控制和愉悦反应，而在背侧纹状体中，5-HT调节运动行为。在此我们表明，在小鼠中，5-HT使背侧纹状体的胆碱能中间神经元（ChIs）去极化，而通过作用于不同的5-HT受体亚型使腹侧纹状体的ChIs超极化。在腹侧纹状体中，5-HT1A（一种突触后受体）和5-HT1B（一种突触前受体）高度表达，并协同抑制ChIs的兴奋性。5-HT1B的抑制性调节（而非5-HT1A的）由与重度抑郁症相关的蛋白质p11介导。从胆碱能神经元中特异性删除5-HT1B会导致腹侧纹状体中乙酰胆碱释放的抑制受损以及出现类似快感缺失的行为。
