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Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making

机译：伏隔核D2R细胞发出先兆信号并控制危险的决策

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摘要

A marked bias towards risk aversion has been observed in nearly every species tested(1-4). 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(2,5). 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 largely explained by the encoding in D2R-expressing NAc cells of prior unfavourable outcomes during decision-making.
机译：在几乎所有测试的物种中都观察到明显的风险规避倾向（1-4）。然而，少数人似乎更喜欢风险（反复选择不确定的较大奖励，而不是某些但较小的奖励），甚至是厌恶风险的人有时也会选择风险更大的选择（2,5）。尚不知道神经活动如何成为决策中如此重要转变的基础-无论是个体之间的稳定特征还是个体内部的可变性。在这里，我们描述了大鼠的风险偏好模型，其中稳定的个体差异，逐次试验选择以及对药理学反应均与人类行为平行。通过将新的遗传靶向策略与该模型中行为期间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了相关的时间特异性信号。这项活动发生在伏伏核（NAc）中表达多巴胺2型受体（D2R）的细胞内，表明最近的过去在有利于影响后续决策的时间产生了不利的结果，并预测了后续的选择。在发现了风险选择的这种自然发生的神经关联之后，我们在决策过程中通过光遗传学控制模仿了时间特异性信号，并证明了其在推动风险偏好方面的因果关系。具体而言，可以通过精确定时的阶段性NAc D2R细胞刺激，将风险偏好的大鼠瞬间转化为风险厌恶的大鼠。这些发现表明，在风险偏好和实时风险决策中的个体差异可以通过在表达D2R的NAc细胞中在决策过程中先前不利结果的编码来很大程度上解释。

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  • 来源
    《Nature》 |2016年第7596期|642-646|共5页
  • 作者

    Zalocusky Kelly A.; Ramakrishnan Charu; Lerner Talia N.; Davidson Thomas J.; Knutson Brian; Deisseroth Karl;

  • 作者单位

    Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA|Stanford Univ, Neurosci Program, Stanford, CA 94305 USA|Stanford Univ, CNC Program, Stanford, CA 94305 USA;

    Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA|Stanford Univ, CNC Program, Stanford, CA 94305 USA;

    Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA|Stanford Univ, CNC Program, Stanford, CA 94305 USA;

    Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA|Stanford Univ, CNC Program, Stanford, CA 94305 USA;

    Stanford Univ, Dept Psychol, Stanford, CA 94305 USA;

    Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA|Stanford Univ, CNC Program, Stanford, CA 94305 USA|Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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