冒险行为可受控制？

冒险行为可受控制？...







冒险行为可受控制？

       都说“一入股市深似海，从此工资是路人”，可见股市有风险，投资需谨慎，然而总有一些人一次又一次勇敢地踏进去。大部分人还是宁愿安安分分的上班有份稳定的薪水，但也不乏有人偏好追求更大的获利机会，从下海经商，创业，到投资股票，买彩票等，尽管这些都存在着全盘皆输的风险。在这个问题上，来自光遗传学之父Karl Deisseroth实验室的 Zalocusky 等人最新的研究发现驾驭一群特定神经元的活动能够使追求风险的动物转变为做风险中性的决策。

说到风险（risk），一般的定义是在人类生活和社会经济活动中发生“不理想事态”的程度以及这种不确定性的大小。所谓风险大，就是指发生不理想事态的可能性或概率高，并带来很大的物质、精神方面的损失。像哥伦布发现新大陆、麦哲伦环球航行等，他们所挑战的航海探险不得不说是冒着很大的风险。在最近一项研究中，斯坦福大学的研究人员对大鼠的冒险偏好行为进行了探索，发现在大鼠中，对冒险偏好和对得失的敏感性的个体差异是由一组特定神经元亚群控制，而刺激这些神经元可以中和冒险行为。

研究人员首先设计了一组实验来检测大鼠在一个决策制定任务中的行为，这个任务有两个选项，每一种都以得到糖果作为奖赏，但又存在糖果大小不同的风险。选择安全选项可以保证每次得到同样大小的糖果奖赏，而选择风险选项则有75%几率得到的是更小块的糖果，只有25%几率会得到更大块的糖果。选到更小块糖果这个结果对于正常期待值来说可算是输了赌注（loss），而获得更大块糖果的结果相对来说则是赢利（win）。

与人类相似，大鼠的决策行为也会受近期的盈损经历所影响。当赢得一次赌博后，几乎所有大鼠在下一次选择中都会再次选择风险赌博选项，而在输了以后会因为“厌恶损失”而倾向于切换到安全选项。然而，有一小群“风险追求者”即使在输了赌博后，后续在继续选择风险赌博与切换到安全赌注之间几乎没有区别。

这背后的神经学机制是什么呢？之前一项人类的研究揭示了个体学会避免损失是由编码多巴胺D2-亚型受体基因的多样性所调节的。另外，人口调查发现病态赌博行为在服用多巴胺D2和D3受体激动剂类药物的帕金森病人中有所增加，比如普拉克索（pramipexole，用于治疗帕金森病）。这些药物会降低人们对“损失”的神经和行为学反应。

研究人员将药物直接传送到大鼠的伏隔核（nucleus accumbens），发现给与大鼠药物普拉克索会导致剂量依赖性的风险追求决策的增加，与人类临床数据相一致。伏隔核位于基底核与边缘系统交界处，是基底前脑的一个较大的核团，在大脑的奖赏, 快乐, 成瘾, 恐惧等活动中起重要作用。Zalocusky等人选择性地靶标伏隔核中表达D2受体的神经元，并利用光遗传学技术对神经元活动进行调控。结果显示，当前一次选择的结果为损失时，下一次大鼠在做选择时伏隔核中D2受体表达细胞的活动普遍要比前一次是收益或者安全选择的结果要更强一些，动物表现为“风险厌恶”。此外，大鼠决定要选择安全选项时D2受体细胞的活动也比选择风险选项时要强些。然而，研究人员发现这些神经信号在大鼠中存在一些个体差异。有些大鼠在输掉前一次的赌博后D2受体细胞的活动没有明显变化，可说是“损失敏感性”（loss sensitivity）相对低一些，并且与行为学相吻合，这些个体继续“追求风险”。这些结果提示个体差异可能归因于伏隔核D2受体细胞的损失敏感性强弱不同，而这种区别可以用来预测动物的冒险偏好。有趣的是，在大鼠做决策期间刺激D2受体表达细胞可以减少冒险型大鼠的赌博行为，而同样的刺激对厌恶损失型大鼠没有影响。这些结果表明伏隔核的D2受体细胞的神经活动会影响动物决策期间的风险偏好。

      在行为金融学中，“厌恶损失”（loss aversion）被用于描述投资者按照自己的心理平衡尺度来做投资决策，绝大多数人对损失和获得的敏感程度是不对称的，即行为经济学“预期理论”提出的损失带来的痛苦远远大于收益给你的满足。当经历了损失时，人们表现为风险厌恶；当经历了收益时，人们则表现为风险追求。Zalocusky和同事的行为学分析数据表明个体在损失敏感性上的差异可能导致冒险偏好的不同，而一些神经元在特定时间点的活动将影响动物的决策行为。这项研究结果为损失厌恶及其对冒险态度的影响提供了潜在生物学解释。

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论文标题：Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making

原文摘要：A marked bias towards risk aversion has been observed in nearly every species tested1, 2, 3, 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 alternatives2, 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.

全文链接：

http://www.nature.com/nature/journal/v531/n7596/full/nature17400.html

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论文标题：Overriding Phasic Dopamine Signals Redirects Action Selection during Risk/Reward Decision Making

原文摘要：Phasic increases and decreases in dopamine (DA) transmission encode reward prediction errors thought to facilitate reward-related learning, yet how these signals guide action selection in more complex situations requiring evaluation of different reward remains unclear. We manipulated phasic DA signals while rats performed a risk/reward decision-making task, using temporally discrete stimulation of either the lateral habenula (LHb) or rostromedial tegmental nucleus (RMTg) to suppress DA bursts (confirmed with neurophysiological studies) or the ventral tegmental area (VTA) to override phasic dips. When rats chose between small/certain and larger/risky rewards, LHb or RMTg stimulation, time-locked to delivery of one of these rewards, redirected bias toward the alternative option, whereas VTA stimulation after nonrewarded choices increased risky choice. LHb stimulation prior to choices shifted bias away from more preferred options. Thus, phasic DA signals provide feedback on whether recent actions were rewarded to update decision policies and direct actions toward more desirable reward.

全文链接：

http://www.sciencedirect.com/science/article/pii/S089662731400734X

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论文标题：Intact-Brain Analyses Reveal Distinct Information Carried by SNc Dopamine Subcircuits

原文摘要：Recent progress in understanding the diversity of midbrain dopamine neurons has highlighted the importance—and the challenges—of defining mammalian neuronal cell types. Although neurons may be best categorized using inclusive criteria spanning biophysical properties, wiring of inputs, wiring of outputs, and activity during behavior, linking all of these measurements to cell types within the intact brains of living mammals has been difficult. Here, using an array of intact-brain circuit interrogation tools, including CLARITY, COLM, optogenetics, viral tracing, and fiber photometry, we explore the diversity of dopamine neurons within the substantia nigra pars compacta (SNc). We identify two parallel nigrostriatal dopamine neuron subpopulations differing in biophysical properties, input wiring, output wiring to dorsomedial striatum (DMS) versus dorsolateral striatum (DLS), and natural activity patterns during free behavior. Our results reveal independently operating nigrostriatal information streams, with implications for understanding the logic of dopaminergic feedback circuits and the diversity of mammalian neuronal cell types.

来源： 脑科学与脑技术

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