Activation, but not inhibition, of the indirect pathway disrupts choice rejection in a freely moving, multiple-choice foraging task
Kristen Delevich,
Benjamin Hoshal,
Lexi Z. Zhou,
Yuting Zhang,
Satya Vedula,
Wan Chen Lin,
Juliana Chase,
Anne G.E. Collins,
Linda Wilbrecht
Affiliations
Kristen Delevich
Department of Psychology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA
Benjamin Hoshal
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
Lexi Z. Zhou
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
Yuting Zhang
Department of Psychology, University of California, Berkeley, Berkeley, CA 94720, USA
Satya Vedula
Department of Psychology, University of California, Berkeley, Berkeley, CA 94720, USA
Wan Chen Lin
Department of Psychology, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA
Juliana Chase
Department of Psychology, University of California, Berkeley, Berkeley, CA 94720, USA
Anne G.E. Collins
Department of Psychology, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA
Linda Wilbrecht
Department of Psychology, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Corresponding author
Summary: 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.
