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通过自然奖赏对多巴胺神经元的瞬时激活进行光遗传学模拟足以进行操作性强化。

Optogenetic mimicry of the transient activation of dopamine neurons by natural reward is sufficient for operant reinforcement.

机构信息

Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.

出版信息

PLoS One. 2012;7(4):e33612. doi: 10.1371/journal.pone.0033612. Epub 2012 Apr 10.

Abstract

Activation of dopamine receptors in forebrain regions, for minutes or longer, is known to be sufficient for positive reinforcement of stimuli and actions. However, the firing rate of dopamine neurons is increased for only about 200 milliseconds following natural reward events that are better than expected, a response which has been described as a "reward prediction error" (RPE). Although RPE drives reinforcement learning (RL) in computational models, it has not been possible to directly test whether the transient dopamine signal actually drives RL. Here we have performed optical stimulation of genetically targeted ventral tegmental area (VTA) dopamine neurons expressing Channelrhodopsin-2 (ChR2) in mice. We mimicked the transient activation of dopamine neurons that occurs in response to natural reward by applying a light pulse of 200 ms in VTA. When a single light pulse followed each self-initiated nose poke, it was sufficient in itself to cause operant reinforcement. Furthermore, when optical stimulation was delivered in separate sessions according to a predetermined pattern, it increased locomotion and contralateral rotations, behaviors that are known to result from activation of dopamine neurons. All three of the optically induced operant and locomotor behaviors were tightly correlated with the number of VTA dopamine neurons that expressed ChR2, providing additional evidence that the behavioral responses were caused by activation of dopamine neurons. These results provide strong evidence that the transient activation of dopamine neurons provides a functional reward signal that drives learning, in support of RL theories of dopamine function.

摘要

已知在前脑区域激活多巴胺受体数分钟或更长时间足以增强对刺激和动作的正强化。然而,在自然奖励事件之后,多巴胺神经元的放电率仅增加约 200 毫秒,这种反应被描述为“奖励预测误差”(RPE)。尽管 RPE 在计算模型中驱动强化学习(RL),但尚未能够直接测试瞬时多巴胺信号实际上是否驱动 RL。在这里,我们在表达 Channelrhodopsin-2(ChR2)的基因靶向腹侧被盖区(VTA)多巴胺神经元的小鼠中进行了光刺激。我们通过在 VTA 中施加 200ms 的光脉冲来模拟自然奖励所引起的多巴胺神经元的瞬时激活。当单个光脉冲在每个自我启动的鼻触之后立即出现时,它本身足以引起操作性强化。此外,当根据预定模式在单独的会话中进行光学刺激时,它会增加运动和对侧旋转,这两种行为已知是由多巴胺神经元的激活引起的。三种光诱导的操作性和运动行为都与表达 ChR2 的 VTA 多巴胺神经元的数量密切相关,这提供了额外的证据表明行为反应是由多巴胺神经元的激活引起的。这些结果提供了有力的证据,表明多巴胺神经元的瞬时激活提供了一种功能性的奖励信号,驱动学习,支持多巴胺功能的 RL 理论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fab8/3323614/94893de6e915/pone.0033612.g001.jpg

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