Temporally restricted dopaminergic control of reward-conditioned movements
Temporally restricted dopaminergic control of reward-conditioned movements
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DOI：
10.1038/s41593-019-0567-0
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发表时间：
2020-01-13
影响因子：
25
通讯作者：
Masmanidis, Sotiris C.
中科院分区：
文献类型：
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作者：
Lee, Kwang;Claar, Leslie D.;Masmanidis, Sotiris C.
中脑多巴胺 (DA) 神经元编码奖励相关事件和运动相关事件，并与奖励处理和运动障碍有关。因此，理清 DA 神经元在增强运动和产生运动中的贡献具有挑战性，并引发了持久的争议。在这项研究中，我们通过参数化地改变巴甫洛夫调节任务中光遗传学操作的时间并检查对奖励传递前预期舔的影响来分离这些功能。在奖励后阶段抑制腹侧被盖区和黑质致密部 DA 神经元比在任务奖励前阶段抑制具有显着更大的行为效果。此外，DA 神经元对行为的贡献随着奖励后经过的时间线性下降。总之，结果表明 DA 神经元的时间限制作用主要与加强刺激-奖励关联有关，并表明直接产生运动是相对不太重要的功能。 在经历了巴甫洛夫奖赏调节的小鼠中，多巴胺能神经元以时间限制的方式调节条件运动，这与对联想学习而不是在线运动生成的主要贡献一致。
Midbrain dopamine (DA) neurons encode both reward- and movement-related events and are implicated in disorders of reward processing as well as movement. Consequently, disentangling the contribution of DA neurons in reinforcing versus generating movements is challenging and has led to lasting controversy. In this study, we dissociated these functions by parametrically varying the timing of optogenetic manipulations in a Pavlovian conditioning task and examining the influence on anticipatory licking before reward delivery. Inhibiting both ventral tegmental area and substantia nigra pars compacta DA neurons in the post-reward period had a significantly greater behavioral effect than inhibition in the pre-reward period of the task. Furthermore, the contribution of DA neurons to behavior decreased linearly as a function of elapsed time after reward. Together, the results indicate a temporally restricted role of DA neurons primarily related to reinforcing stimulus-reward associations and suggest that directly generating movements is a comparatively less important function.In mice that have undergone Pavlovian reward conditioning, dopaminergic neurons regulate conditioned movements in a temporally restricted manner, consistent with a primary contribution to associative learning rather than online movement generation.