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.
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell Rep. 2022 Jul 26;40(4):111129. doi: 10.1016/j.celrep.2022.111129.
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.
背内侧纹状体（DMS）在动作选择中起着关键作用，但对于直接和间接通路棘突投射神经元（分别为 dSPNs 和 iSPNs）如何有助于在自由活动的动物中拒绝选择，人们知之甚少。在这里，我们在一个序列选择觅食任务中使用特定通路的化学遗传学操作来测试 dSPNs 和 iSPNs 在学习性选择拒绝中的作用。我们发现，iSPNs 的化学遗传激活而非抑制会破坏对无回报选择的拒绝，这与简单的“选择/抑制”启发式的预测相反。我们的发现表明，iSPNs 在停止和冻结方面的作用并不能简单地扩展到自由活动的行为学背景下的选择拒绝。这些数据可能为成功设计干预成瘾或其他希望增强选择拒绝的疾病的干预措施提供关键见解。
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