Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making.
Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making.
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DOI：
10.1038/nature17400
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发表时间：
2016-03-31
期刊：
影响因子：
64.8
通讯作者：
Deisseroth K
中科院分区：
文献类型：
--
作者：
Zalocusky KA;Ramakrishnan C;Lerner TN;Davidson TJ;Knutson B;Deisseroth K
几乎在所有测试的物种中都观察到了对风险规避的明显偏见。然而，少数人似乎更喜欢风险（反复选择不确定的大回报，而不是确定但较小的回报），甚至厌恶风险的人有时也会选择风险更高的替代品。目前还不清楚神经活动是如何成为决策过程中如此重要的变化的基础的--无论是作为个体之间的稳定特征，还是在个体内部的变异水平。在这里，我们描述了一个模型的风险偏好的大鼠，其中稳定的个体差异，试验的试验选择，并响应药理剂所有平行的人类行为。通过将新的遗传靶向策略与该模型中行为过程中神经活动的光学记录相结合，我们从遗传和解剖学定义的神经元群体中识别出相关的时间特异性信号。这种活动发生在多巴胺受体2型（D2 R）的表达细胞中的神经核（NAc），信号从最近的过去在适当的时间影响随后的决定不利的结果，也预测了随后的选择。在揭示了这种自然发生的风险选择神经相关性之后，我们在决策过程中用光遗传学控制模拟了时间特异性信号，并证明了其在驱动风险偏好方面的因果效应。具体来说，风险偏好的大鼠可以立即转换为风险厌恶的大鼠与精确定时的阶段性刺激NAc D2 R细胞。这些研究结果表明，风险偏好的个体差异，以及实时风险决策，可以在很大程度上解释的编码在D2 R表达NAc细胞的决策过程中先前不利的结果。
A marked bias towards risk aversion has been observed in nearly every species tested. A minority of individuals, however, instead seem to prefer risk (repeatedly choosing uncertain large rewards over certain but smaller rewards), and even risk-averse individuals sometimes opt for riskier alternatives. It is not known how neural activity underlies such important shifts in decision-making—either as a stable trait across individuals or at the level of variability within individuals. Here we describe a model of risk-preference in rats, in which stable individual differences, trial-by-trial choices, and responses to pharmacological agents all parallel human behaviour. By combining new genetic targeting strategies with optical recording of neural activity during behaviour in this model, we identify relevant temporally specific signals from a genetically and anatomically defined population of neurons. This activity occurred within dopamine receptor type-2 (D2R)-expressing cells in the nucleus accumbens (NAc), signalled unfavourable outcomes from the recent past at a time appropriate for influencing subsequent decisions, and also predicted subsequent choices made. Having uncovered this naturally occurring neural correlate of risk selection, we then mimicked the temporally specific signal with optogenetic control during decision-making and demonstrated its causal effect in driving risk-preference. Specifically, risk-preferring rats could be instantaneously converted to risk-averse rats with precisely timed phasic stimulation of NAc D2R cells. These findings suggest that individual differences in risk preference, as well as real-time risky decision-making, can be in large part explained by the encoding in D2R-expressing NAc cells of prior unfavourable outcomes during decision-making.
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