Benjamin Hoshal – Wilbrecht Lab

Activation, but not inhibition, of the indirect pathway disrupts choice rejection in a freely moving, multiple-choice foraging task

The dorsomedial striatum (DMS) plays a key role in action selection, but less is known about how direct and indirect pathway spiny projection neurons (dSPNs and iSPNs, respectively) contribute to choice rejection in freely moving animals. Here, we use pathway-specific chemogenetic manipulation during a serial choice foraging task to test the role of dSPNs and iSPNs in learned choice rejection. We find that chemogenetic activation, but not inhibition, of iSPNs disrupts rejection of nonrewarded choices, contrary to predictions of a simple “select/suppress” heuristic. Our findings suggest that iSPNs’ role in stopping and freezing does not extend in a simple fashion to choice rejection in an ethological, freely moving context. These data may provide insights critical for the successful design of interventions for addiction or other conditions in which it is desirable to strengthen choice rejection.

Kristen Delevich, Benjamin Hoshal, Lexi Z. Zhou, Yuting Zhang, Satya Vedula, Wan Chen Lin, Juliana Chase, Anne G.E. Collins, Linda Wilbrecht, Activation, but not inhibition, of the indirect pathway disrupts choice rejection in a freely moving, multiple-choice foraging task, 40(4) Cell Reports 111129 (July 26, 2022). DOI: https://doi.org/10.1016/j.celrep.2022.111129

Choice suppression is achieved through opponent but not independent function of the striatal indirect pathway in mice

The dorsomedial striatum (DMS) plays a key role in action selection, but little is known about how direct and indirect pathway spiny projection neurons (dSPNs and iSPNs) contribute to choice suppression in freely moving animals. Here, we used pathway-specific chemogenetic manipulation during a serial choice foraging task to test opposing predictions for iSPN function generated by two theories: 1) the ‘select/suppress’ heuristic which suggests iSPN activity is required to suppress alternate choices and 2) the network-inspired Opponent Actor Learning model (OpAL) which proposes that the weighted difference of dSPN and iSPN activity determines choice. We found that chemogenetic activation, but not inhibition, of iSPNs disrupted learned suppression of nonrewarded choices, consistent with the predictions of the OpAL model. Our findings suggest that iSPNs’ role in stopping and freezing does not extend in a simple fashion to choice suppression. These data may provide insights critical for the successful design of interventions for addiction or other conditions in which suppression of behavior is desirable.

Kristen Delevich, Benjamin Hoshal, Anne GE Collins, Linda Wilbrecht, Choice suppression is achieved through opponent but not independent function of the striatal indirect pathway in mice, BioRxiv, https://www.biorxiv.org/content/10.1101/675850v3
doi: https://doi.org/10.1101/675850