The role of midbrain dopamine neurons in reward prediction and reward seeking

为了在生存和繁殖的斗争中取得成功，动物必须做出明智的选择，决定追求哪些目标，以及为实现这些目标需要付出多大的代价和承担多大的风险。大脑是如何做出这样的决定并相应地调整行为的？神经生物学家、计算机科学家和心理学家合作开发了一个有影响力的理论来回答这些问题。该理论认为，大脑中的多巴胺细胞调整了对奖励预测的准确性，并为寻求奖励的行为设定了价值。这些多巴胺神经元的活动被认为反映了预期结果和已经发生的结果之间的差异。这种多巴胺信号提供反馈，以改善对未来结果的预测，并选择实现这些结果所需的行动。一系列新的实验将在研究多巴胺细胞视觉激活的大鼠身上测试预测误差理论。当老鼠的预测和寻求奖励的行为被测量时，多巴胺的释放将被微型化学传感器监测。在遇到有价值的奖励（如高营养的食物）后，觅食者立即寻找另一个是有意义的。奖励越有价值，觅食者就应该越努力地这样做。这种适应性机会主义行为已经在实验鼠的脑部电刺激奖励中得到证实。多巴胺神经元与寻求奖励密切相关，然而，在暴露于强电奖励后，寻求奖励的增强并没有因为阻断大脑中多巴胺作用的药物而减少。我们将通过用多巴胺神经元的直接、特异性、光学激活取代电刺激产生的间接、非特异性激活来解决这一矛盾。研究结果将帮助我们理解多巴胺神经元在动机中的作用。***动物对潜在利益、损害、成本和风险的评估必须取决于其当前的生理状态。由于体内储存的能量耗尽，寻找食物变得势在必行，动物愿意采取昂贵而冒险的行动来实现这一目标。长期以来，我们一直在研究脑电刺激下大鼠寻求奖励对能量平衡的依赖性。最近，我们应用了一种新的方法来区分能量消耗对奖励的敏感性（这会使食物看起来更有价值）和动物对获得奖励所涉及的成本的评估（这会使食物看起来更便宜）的影响。我现在建议用多巴胺神经元的光刺激来代替我们之前使用的电刺激，电刺激的特异性较低，并且间接激活多巴胺神经元。这项工作将帮助我们更好地理解多巴胺神经元是否以及如何将奖励追求与内部生理环境状态联系起来。

To succeed in their struggle for survival and reproductive success, animals must make wise choices about which goals to pursue and how much to pay and risk to attain them. How does the brain make such decisions and adjust behaviour accordingly? Neurobiologists, computer scientists, and psychologists have collaborated in developing an influential theory to answer these questions. The theory holds that dopamine cells in the brain adjust the accuracy of predictions about rewards and set the values assigned to reward-seeking actions. The activity of these dopamine neurons is posited to reflect the difference between the consequences that are expected and those that come to pass. This dopamine signal provides feedback to improve predictions of future outcomes and to choose the actions required to achieve them. One line of novel experiments will test the prediction-error theory in rats working for optical activation of dopamine cells. The release of dopamine will be monitored by miniature chemical sensors as the rats' predictions and reward-seeking actions are measured.*** After encountering a valuable reward, such as a highly nutritious food item, it makes sense for a forager to immediately seek another. The more valuable the reward, the more vigorously the forager should do this. Such adaptively opportunistic behaviour has been documented in rats working for rewarding electrical brain stimulation. Dopamine neurons have been implicated strongly in reward seeking, yet the potentiation of reward seeking following exposure to a strong electrical reward was not reduced by a drug that blocks dopamine action in the brain. We will address this paradox by substituting direct, specific, optical activation of dopamine neurons for the indirect, non-specific activation produced by electrical stimulation. The results will help us understand the role of dopamine neurons in motivation.*** An animal's assessment of potential benefits, detriments, costs, and risks must depend on its current physiological state. As internal energy stores empty, finding food becomes imperative, and the animal is willing to pursue expensive, risky courses of action to achieve this goal. We have long studied the dependence of reward seeking on energy balance in rats working for rewarding electrical brain stimulation. Recently, we applied a new method that distinguishes the effects of energy depletion on sensitivity to reward (which would make a food item seem more valuable) and on the animal's assessment of the costs involved in procuring the reward (which would make a food item seem cheaper). I now propose to substitute optical stimulation of dopamine neurons for the electrical stimulation we have used previously, which is less specific and activates dopamine neurons indirectly. This work will help us better understand whether and how dopamine neurons link reward pursuit to the state of the internal physiological environment.