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Published on: September 10, 2018
Activation, but not inhibition, of the indirect pathway disrupts choice rejection in a freely moving, multiple-choice
Kristen Delevich1, Benjamin Hoshal2, Lexi Z Zhou2
1Department 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.
Abstract:
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.
Insights
In freely moving animals, activating indirect pathway spiny projection neurons (iSPNs) impaired the rejection of nonrewarded choices. This suggests iSPNs' role in stopping does not directly translate to choice rejection in naturalistic settings.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
Background:
- The dorsomedial striatum (DMS) is crucial for action selection.
- The specific roles of direct (dSPN) and indirect (iSPN) pathway spiny projection neurons in choice rejection remain unclear, especially in freely moving animals.
Purpose of the Study:
- To investigate the contribution of dSPNs and iSPNs to learned choice rejection using pathway-specific chemogenetics.
- To test the hypothesis that iSPNs mediate the suppression of nonrewarded choices.
Main Methods:
- Chemogenetic manipulation of iSPNs and dSPNs in mice during a serial choice foraging task.
- Behavioral analysis of choice rejection in response to pathway-specific neuronal activation or inhibition.
Main Results:
- Activation of iSPNs significantly disrupted the rejection of nonrewarded choices.
- Inhibition of iSPNs did not affect choice rejection.
- These findings challenge simple "select/suppress" models of action selection.
Conclusions:
- The role of iSPNs in stopping and freezing behaviors does not directly predict their function in choice rejection in an ethological context.
- Understanding iSPN function in choice rejection may inform interventions for conditions like addiction.
