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Opposing roles for serotonin in cholinergic neurons of the ventral and dorsal striatum.

TitleOpposing roles for serotonin in cholinergic neurons of the ventral and dorsal striatum.
Publication TypeJournal Article
Year of Publication2016
AuthorsVirk MS, Sagi Y, Medrihan L, Leung J, Kaplitt MG, Greengard P
JournalProc Natl Acad Sci U S A
Volume113
Issue3
Pagination734-9
Date Published2016 Jan 19
ISSN1091-6490
KeywordsAcetylcholine, Animals, Behavior, Animal, Cholinergic Neurons, Gene Deletion, Interneurons, Mice, Inbred C57BL, Mice, Knockout, Neostriatum, Receptors, Serotonin, Serotonin
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.

DOI10.1073/pnas.1524183113
Alternate JournalProc Natl Acad Sci U S A
PubMed ID26733685
PubMed Central IDPMC4725497
Grant ListP01 DA010044 / DA / NIDA NIH HHS / United States
DA010044 / DA / NIDA NIH HHS / United States