Abstract：
Transient nigrostriatal dopaminergic signalling is well known for its role in reinforcement learning and increasingly so for its role in the initiation of voluntary movement. However, how transient bursts of dopamine modulate voluntary movement remains unclear, likely due to the heterogeneity of the nigrostriatal system, the focus of optogenetic studies on locomotion at sub-sec time intervals, and the overlapping roles of phasic dopamine in behaviour and novelty signalling. In this study we investigated how phasic activity in the lateral substantia nigra pars compacta (lateral SNc) over time affects voluntary behaviours during exploration. Using a transgenic mouse model of both sexes expressing channelrhodopsin (ChR2) in dopamine transporter-expressing cells, we stimulated the lateral SNc while mice explored an open field over two consecutive days. We found that phasic activation of the lateral SNc induced an increase in exploratory behaviours including horizontal movement activity, locomotion initiation, and rearing specifically on the first open field exposure, but not on the second day. In addition, stimulated animals did not habituate to the same extent as their ChR2-negative counterparts, as indicated by a lack of decrease in baseline activity. These findings suggest that rather than prompting voluntary movement in general, phasic nigrostriatal dopamine prompts context-appropriate behaviours. In addition, dopamine signalling that modulates movement acts over longer timescales than the transient signal, affecting behaviour even after the signal has ended.
摘要：
瞬时黑质纹状体多巴胺能信号在强化学习中的作用以及在自主运动开始中的作用越来越众所周知。然而,多巴胺的瞬时爆发如何调节自主运动仍不清楚，可能是由于黑质纹状体系统的异质性，以亚秒时间间隔运动的光遗传学研究的重点，以及阶段性多巴胺在行为和新奇信号中的重叠作用。在这项研究中，我们调查了随着时间的推移，黑质旁侧（横向SNc）的阶段性活动如何影响探索过程中的自愿行为。使用在多巴胺转运蛋白表达细胞中表达通道视紫红质（ChR2）的两性的转基因小鼠模型，当小鼠连续两天探索开放区域时，我们刺激了侧向SNc。我们发现，横向SNc的阶段性激活诱导了包括水平运动活动在内的探索行为的增加，运动启动，特别是在第一次公开曝光时，但不是在第二天。此外,受刺激的动物没有像它们的ChR2阴性对应物那样习惯，如基线活动缺乏减少所示。这些发现表明，总体上不是促使自愿运动，阶段性黑质纹状体多巴胺会提示上下文适当的行为。此外,调节运动的多巴胺信号在比瞬态信号更长的时间尺度上起作用，即使在信号结束后也会影响行为。
