Multiphasic temporal dynamics in responses of midbrain dopamine neurons to appetitive and aversive stimuli.
Multiphasic temporal dynamics in responses of midbrain dopamine neurons to appetitive and aversive stimuli.
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DOI：
10.1523/jneurosci.3883-12.2013
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发表时间：
2013-03-13
期刊：
影响因子：
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通讯作者：
Yun SR
中科院分区：
文献类型：
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作者：
Fiorillo CD;Song MR;Yun SR
多巴胺神经元的瞬时反应被描述为奖励预测误差（RPE），分别由比预期更好或更差的事件激活或抑制。然而，至少有少数神经元被厌恶或高强度刺激激活，对RPE在描述多巴胺信号方面的普遍性提出了质疑。为了克服以往研究的局限性，我们研究了神经元对更广泛的各种高强度和厌恶刺激的反应，我们通过选择任务，猕猴牺牲果汁，以避免厌恶刺激量化和控制厌恶。而大多数以前的工作描绘的RPE作为一个单一的脉冲或“阶段”，在这里，我们展示了其多相的时间动态。在40-700 ms的时间内，厌恶性或高强度刺激诱发了一个激活-抑制-激活的三相序列，在短潜伏期（40-120 ms）的初始激活反映了感觉强度，在150~250 ms之间，动机价值的影响开始占主导地位，在食欲刺激的情况下激活，在厌恶性和中性刺激的情况下抑制。先前未报告的晚期激活似乎是强烈抑制后的适度"反弹"。类似地，奖励的强烈激活往往伴随着抑制。我们认为，这些“反弹”可能是由于过度补偿的稳态机制在某些细胞。我们的研究结果与现实的RPE一致，RPE通过兴奋和抑制的动态平衡随时间推移而演变
The transient response of dopamine neurons has been described as reward prediction error (RPE), with activation or suppression by events that are better or worse than expected, respectively. However, at least a minority of neurons are activated by aversive or high-intensity stimuli, casting doubt on the generality of RPE in describing the dopamine signal. To overcome limitations of previous studies, we studied neuronal responses to a wider variety of high-intensity and aversive stimuli, and we quantified and controlled aversiveness through a choice task in which macaques sacrificed juice to avoid aversive stimuli. Whereas most previous work has portrayed the RPE as a single impulse or “phase,” here we demonstrate its multiphasic temporal dynamics. Aversive or high-intensity stimuli evoked a triphasic sequence of activation-suppression-activation extending over a period of 40–700 ms. The initial activation at short latencies (40–120 ms) reflected sensory intensity.The influence of motivational value became dominant between 150 and 250 ms, with activation in the case of appetitive stimuli, and suppression in the case of aversive and neutral stimuli. The previously unreported late activation appeared to be a modest “rebound” after strong suppression. Similarly, strong activation by reward was often followed by suppression. We suggest that these “rebounds” may result from overcompensation by homeostatic mechanisms in some cells. Our results are consistent with a realistic RPE, which evolves over time through a dynamic balance of excitation and inhibition