ePoster

Indirect-projecting striatal neurons constrain timed action via ‘ramping’ activity.

Robert Bruce,Rachael Volkman,Nandakumar Narayanan
COSYNE 2022(2022)
Lisbon, Portugal

Conference

COSYNE 2022

Lisbon, Portugal

Resources

Authors & Affiliations

Robert Bruce,Rachael Volkman,Nandakumar Narayanan

Abstract

Time represents a fundamental dimension around which all behaviors must be organized. Previous work has shown that dorsal striatal medium spiny neurons (MSNs) encode prospective time via ‘ramping’, progressive linear increases or decreases in firing rate preceding a time at which an animal must act (Emmons et al., 2017; Matell et al., 2003). Furthermore, disruptions to dopamine signaling attenuate this pattern of activity and can bidirectionally modulate performance of timed behaviors (Parker et al., 2015; Soares et al., 2016). Dopamine binds to both D1- and D2-MSNs which play orthogonal roles in movement and reinforcement learning (Kravitz & Kreitzer, 2012). However, the respective roles of D1- and D2-MSNs in timing remain poorly understood. Here, we trained transgenic D1- and D2-cre mice to perform an operant interval timing task which required mice to ‘switch’ response ports after 6 seconds had passed without receiving a reward. In our first experiment, we utilized cell-type specific optogenetics to selectively inhibit either D1- or D2-MSNs and found that D2-MSN inhibition resulted in impaired temporal accuracy. To better understand the in-vivo dynamics underlying this effect, we then recorded from optically tagged D1- and D2-MSNs and observed ‘ramping’ activity amongst a greater proportion of D2-MSNs than D1-MSNs. Finally, we pharmacologically blockaded dopamine binding to either D1- or D2-dopamine receptors with either systemic SCH23390 or sulpiride. Interestingly, we found that D2 receptor blockade, but not D1 receptor blockade, attenuated time-related activity across striatal ensembles although both drugs attenuated movement-associated activity. These results suggest that time-related ramping amongst D2-MSNs may constrain behavior during a timed interval, a process which can be captured by drift-diffusion models. These data are of particular interest for understanding the circuit mechanisms of impaired temporal control of action in disease states involving striatal dysfunction, such as Parkinson’s disease and Huntington’s disease.

Unique ID: cosyne-22/indirectprojecting-striatal-neurons-69297365