THE CHOLINERGIC TAN SYSTEM IN DISTINCT REGIONS OF THE PRIMATE DORSAL STRIATUM MAKES DIFFERENT CONTRIBUTIONS TO FLEXIBLE SWITCHING BETWEEN TWO STIMULUS–RESPONSE RULES

Local cholinergic transmission of the striatum is of increasing interest due to research showing its involvement in adaptive behavior and neuropsychiatric disorders. While this system is related to context recognition which is important for reinforcement learning and flexibility in action selection, it remains unclear whether this role can vary across different striatal regions. We addressed this question by recording tonically active neurons (TANs), putative cholinergic interneurons, from distinct regions of the dorsal striatum, in one macaque monkey trained to switch between two different stimulus-response rules linking a colored trigger stimulus with a motor response to the left, center, or right. Switching from one rule to another resulted in slower performance, reflecting higher demands for adapting behavior, and we examined the TAN activity around each switch in the motor (n=73) and associative (n=59) parts of the striatum. The responsiveness of TANs to the trigger stimulus was evaluated based on the two consecutive phasic response components typically seen in these neurons: a pause followed by a rebound in firing. By investigating response dynamics associated with the switch, we found that the pause showed little modulation related to rule switching in both striatal regions, whereas the magnitude of the rebound was strengthened specifically in the motor part. These data suggest that distinct components of the TAN response contribute to adjusting behavior during rule switching, with region-specific differences in response properties. Our experiments currently in progress investigate whether chemogenetic inactivation of the cholinergic TAN system may disrupt the adaptive shift in behavior.