Activation of the Rostral Intralaminar Thalamus Drives Reinforcement through Striatal Dopamine Release.

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. Graphical Abstract Highlights • The rostral intralaminar nuclei of the thalamus (rILN) project to the dorsal striatum • Glutamatergic rILN projections induce local dopamine release in the dorsal striatum • rILN activity suppression correlates with reduced nigrostriatal activity and movement • rILN terminal activation supports behavioral reinforcement Cover et al. identify a glutamatergic thalamostriatal pathway that locally elicits striatal dopamine release to drive reward-related behavior in mice. [ABSTRACT FROM AUTHOR]