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

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