Risk of punishment influences discrete and coordinated encoding of reward-guided actions by prefrontal cortex and VTA neurons.
Risk of punishment influences discrete and coordinated encoding of reward-guided actions by prefrontal cortex and VTA neurons.
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DOI：
10.7554/elife.30056
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发表时间：
2017-10-23
期刊：
影响因子：
7.7
通讯作者：
Moghaddam B
中科院分区：
文献类型：
--
作者：
Park J;Moghaddam B
受奖励驱动的行为往往伴随着受惩罚的风险。在寻求奖励的行为过程中，对于惩罚风险的神经表征人们知之甚少。我们通过设计一项任务在大鼠身上模拟这种情况，在该任务中，行为总是能得到奖励，但有一定概率会受到惩罚。在任务执行过程中，同时从腹侧被盖区（VTA）和内侧前额叶皮层（mPFC）记录到了锋电位活动和局部场电位，这两个相互连接的区域与寻求奖励和厌恶行为有关。在单细胞水平上，我们发现假定的多巴胺能和非多巴胺能的VTA神经元以及mPFC神经元群对行为和惩罚之间的关系进行编码。在网络水平上，我们发现相干的θ振荡在自下而上的方向上使VTA和mPFC同步，在无惩罚行为期间有效地对两个区域的神经元锋电位活动进行相位调制。这种同步性随着惩罚概率的增加而降低，这表明在寻求奖励的行为过程中，惩罚的风险会减弱两个区域之间由VTA驱动的神经同步性。
在决定做什么时，我们通常会尝试预测我们行为可能产生的结果。这有助于我们选择会带来积极结果（即奖励）的行为，并避免那些会带来消极结果（即惩罚）的行为。但在实际情况中，有可能带来奖励的行为往往涉及不同程度的风险。例如，当动物觅食时，它们有遇到捕食者的风险。在我们复杂的社会环境中，申请工作或邀请某人约会意味着有被拒绝的风险。能够权衡积极和消极结果的可能性对有效决策至关重要。
帕克（Park）和莫哈达姆（Moghaddam）现在已经研究了大脑的奖励系统是如何考虑可能的消极结果的。大鼠学会了在测试箱内的灯亮起时将鼻子伸进一个窗口，以获得一份糖作为奖励。大鼠完成了三组试验。在第一组试验中，它们只得到奖励。但在第二组和第三组试验中的一些试验里，它们在获得奖励的同时还会受到轻微的电击。
在整个任务过程中，帕克和莫哈达姆监测了大脑中编码奖励的两个区域的活动，即腹侧被盖区（简称VTA）和内侧前额叶皮层。VTA位于大脑深处，会产生大脑的奖励化学物质——多巴胺。前额叶皮层位于大脑前部，有助于支持认知。在只有奖励的试验组中，VTA中的神经元与前额叶皮层中的神经元同步放电。在有电击风险的第二组和第三组试验中，这种同步性降低了。这表明当可能出现不愉快的结果时，前额叶皮层会对决策进行更强的控制。
一贯高估事情出错的风险会导致焦虑。低估风险会导致冲动和决策失误。帕克和莫哈达姆的实验提供了一种在动物身上研究这些过程背后机制的方法。研究结果还表明，在临床试验中，使用头皮电极追踪患者前额叶皮层的活动可能对焦虑或冲动控制障碍的研究有帮助。
Actions motivated by rewards are often associated with risk of punishment. Little is known about the neural representation of punishment risk during reward-seeking behavior. We modeled this circumstance in rats by designing a task where actions were consistently rewarded but probabilistically punished. Spike activity and local field potentials were recorded during task performance simultaneously from VTA and mPFC, two reciprocally connected regions implicated in reward-seeking and aversive behaviors. At the single unit level, we found that ensembles of putative dopamine and non-dopamine VTA neurons and mPFC neurons encode the relationship between action and punishment. At the network level, we found that coherent theta oscillations synchronize VTA and mPFC in a bottom-up direction, effectively phase-modulating the neuronal spike activity in the two regions during punishment-free actions. This synchrony declined as a function of punishment probability, suggesting that during reward-seeking actions, risk of punishment diminishes VTA-driven neural synchrony between the two regions. When deciding what to do, we usually try to predict the likely outcomes of our actions. This helps us choose behaviors that will lead to positive outcomes, or rewards, and avoid those that will lead to negative outcomes, or punishments. But in practice, actions that offer the possibility of reward often involve varying degrees of risk. When animals forage for food, for example, they risk encountering a predator. In our complex social world, applying for a job or asking someone out on a date means risking rejection. Being able to weigh up the likelihood of positive and negative outcomes is vital for effective decision-making. Park and Moghaddam have now studied how the brain’s reward system takes account of possible negative outcomes. Rats learned to poke their noses into a window inside a testing box whenever a light came on, to earn a sugar reward. The rats completed three blocks of trials. During the first block, they received only rewards. But for a few trials during the second and third blocks, they also received a mild electric shock as well as their reward. Throughout the task, Park and Moghaddam monitored the activity of two regions of the brain that encode rewards, the ventral tegmental area (or VTA for short) and the medial prefrontal cortex. The VTA sits deep within the brain and produces the brain’s reward chemical, dopamine. The prefrontal cortex is at the front of the brain and helps support cognition. In the reward-only block of trials, neurons in the VTA synchronized their firing with neurons in the prefrontal cortex. In blocks two and three, where there was a risk of shock, this synchrony decreased. This suggests that the prefrontal cortex takes greater control of decision-making when an unpleasant outcome is possible. Consistently overestimating the risk of things going wrong will lead to anxiety. Underestimating the risks will lead to impulsivity and poor decision-making. Park and Moghaddam’s experiment offers a way to study the mechanisms underlying these processes in animals. The results also suggest that using scalp electrodes to track prefrontal cortex activity in patients could be helpful in clinical trials for anxiety or impulse-control disorders.