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 |