Activation of the Rostral Intralaminar Thalamus Drives Reinforcement through Striatal Dopamine Release
Kara K. Cover,
Utsav Gyawali,
Willa G. Kerkhoff,
Mary H. Patton,
Chaoqi Mu,
Michael G. White,
Ashley E. Marquardt,
Bradley M. Roberts,
Joseph F. Cheer,
Brian N. Mathur
Affiliations
Kara K. Cover
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Utsav Gyawali
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Willa G. Kerkhoff
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Mary H. Patton
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Chaoqi Mu
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Michael G. White
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Ashley E. Marquardt
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Bradley M. Roberts
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Joseph F. Cheer
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Brian N. Mathur
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Corresponding author
Summary: Glutamatergic 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. : Cover et al. identify a glutamatergic thalamostriatal pathway that locally elicits striatal dopamine release to drive reward-related behavior in mice. Keywords: goal-directed behavior, caudate, putamen, associative thalamus, movement, Parkinson’s disease, addiction
