Optogenetic mimicry of the transient activation of dopamine neurons by natural reward is sufficient for operant reinforcement.
Optogenetic mimicry of the transient activation of dopamine neurons by natural reward is sufficient for operant reinforcement.
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DOI：
10.1371/journal.pone.0033612
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fiorillo CD
中科院分区：
文献类型：
--
作者：
Kim KM;Baratta MV;Yang A;Lee D;Boyden ES;Fiorillo CD
多巴胺受体在前脑区域的激活，几分钟或更长时间，被认为是足够的积极强化刺激和行动。然而，多巴胺神经元的放电率在自然奖励事件发生后仅增加约200毫秒，这种反应被描述为“奖励预测误差”（RPE）。尽管在计算模型中RPE驱动强化学习（RL），但目前还无法直接测试瞬时多巴胺信号是否真的驱动RL。在这里，我们对小鼠的基因靶向腹侧被盖区（VTA）多巴胺神经元进行了光刺激，该神经元表达通道视紫红质-2 （ChR2）。我们通过在VTA中施加200毫秒的光脉冲来模拟多巴胺神经元在自然奖励反应中发生的短暂激活。当一个单一的光脉冲跟随每一个自我启动的鼻子戳，它本身就足以引起操作性强化。此外，当光刺激按照预定的模式在不同的会话中传递时，它会增加运动和对侧旋转，这些行为已知是由多巴胺神经元激活引起的。所有三种光诱导的操作和运动行为都与表达ChR2的VTA多巴胺神经元数量密切相关，这进一步证明了行为反应是由多巴胺神经元激活引起的。这些结果提供了强有力的证据，证明多巴胺神经元的短暂激活提供了驱动学习的功能性奖励信号，支持多巴胺功能的RL理论。
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.
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影响因子：
3.4
作者：
Easterling, KW;Plovnick, RM;Holtzman, SG
通讯作者：
Holtzman, SG
影响因子：
2.9
作者：
NAKAHARA, D;FUCHIKAMI, K;NAGATSU, T
通讯作者：
NAGATSU, T
影响因子：
25
作者：
Boyden, ES;Zhang, F;Deisseroth, K
通讯作者：
Deisseroth, K
DOI：
10.1523/jneurosci.2246-11.2011
发表时间：
2011-07-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Adamantidis AR;Tsai HC;Boutrel B;Zhang F;Stuber GD;Budygin EA;Touriño C;Bonci A;Deisseroth K;de Lecea L
通讯作者：
de Lecea L
影响因子：
56.9
作者：
Fiorillo, CD;Tobler, PN;Schultz, W
通讯作者：
Schultz, W