Activation of the Rostral Intralaminar Thalamus Drives Reinforcement through Striatal Dopamine Release
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AbstractGlutamatergic projections of the thalamic rostral intralaminar nuclei of the thalamus (rILN) innervate the dorsal striatum (DS) and are implicated in dopamine (DA)-dependent incubation of drug seeking. However, the mechanism by which rILN signaling modulates reward seeking and striatal DA release is unknown. We find that activation of rILN inputs to the DS drives cholinergic interneuron burst-firing behavior and DA D2 receptor-dependent post-burst pauses in cholinergic interneuron firing. In vivo, optogenetic activation of this pathway drives reinforcement in a DA D1 receptor-dependent manner, and chemogenetic suppression of the rILN reduces dopaminergic nigrostriatal terminal activity as measured by fiber photometry. Altogether, these data provide evidence that the rILN activates striatal cholinergic interneurons to enhance the pursuit of reward through local striatal DA release and introduce an additional level of complexity in our understanding of striatal DA signaling. © 2019 The Authors
SponsorsThis work was supported by the University of Maryland Claude D. Pepper Older Americans Independence Center; National Institute on Alcohol Abuse and Alcoholism grants K22AA021414 , R01AA024845 (to B.N.M.), and F31AA024683 (to M.H.P.); Whitehall Foundation grant 2014-12-68 (B.N.M.); National Institute on Drug Abuse grants R01DA022340 , R01DA042595 (to J.F.C.), and F31DA047014 (to K.K.C.); and National Institute of Neurological Disorders and Stroke grant T32NS063391 (to K.K.C.).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85060750364&doi=10.1016%2fj.celrep.2019.01.044&partnerID=40&md5=be3bdbb7bd31c2f06fa8b23f45f45b4f; http://hdl.handle.net/10713/8654
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