title: Opposing roles for serotonin in cholinergic neurons of the ventral and dorsal striatum.
abstract: 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.
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065; Department of Neurosurgery, Weill Cornell Medical Center, New York, NY 10065; miv2010@nyp.org ysagi@rockefeller.edu greengard@rockefeller.edu.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Virk
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065; miv2010@nyp.org ysagi@rockefeller.edu greengard@rockefeller.edu.
authors.forename: Yotam
authors.initials: Y
authors.lastname: Sagi
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065;
authors.forename: Lucian
authors.initials: L
authors.lastname: Medrihan
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065;
authors.forename: Jenny
authors.initials: J
authors.lastname: Leung
authors.affiliation: Laboratory of Molecular Neurosurgery, Weill Medical College of Cornell University, New York, NY 10065.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kaplitt
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065; miv2010@nyp.org ysagi@rockefeller.edu greengard@rockefeller.edu.
authors.forename: Paul
authors.initials: P
authors.lastname: Greengard
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D059329:Cholinergic Neurons / Q000378:metabolism*; D017353:Gene Deletion; D007395:Interneurons / Q000166:cytology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017072:Neostriatum / Q000166:cytology*; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*
chemical_list: D011985:Receptors, Serotonin; D012701:Serotonin; D000109:Acetylcholine
keywords: 5-HT1A; 5-HT1B; TRAP; cholinergic interneurons; ventral striatum