Publication Type Academic Article
Authors Virk M, Sagi Y, Medrihan L, Leung J, Kaplitt M, Greengard P
Journal Proc Natl Acad Sci U S A
Volume 113
Issue 3
Pagination 734-9
Date Published 01/05/2016
ISSN 1091-6490
Keywords Cholinergic Neurons, Neostriatum, 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.
DOI 10.1073/pnas.1524183113
PubMed ID 26733685
PubMed Central ID PMC4725497
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