Context dependent modulations of dopamine signaling

项目摘要 多巴胺被认为是从胃口和厌恶事件中学习的关键调节器。一直以来 提出了多巴胺神经元信号值预测误差(VPE，通常称为奖赏预测 误差)，即实际结果和预测结果之间的差值。尽管不断积累的证据 支持这种奖励的想法，多巴胺神经元如何整合关于厌恶事件的信息仍然存在 极具争议性。一些研究表明，厌恶刺激会抑制多巴胺神经元，而另一些研究则表明 已经表明，厌恶事件至少激活了一些多巴胺神经元。其他人则认为 多巴胺神经元在很大程度上忽略了厌恶事件。为了解决上述争议，本项目旨在 为了研究腹侧被盖区(VTA)中的多巴胺神经元如何传递关于厌恶的信息 事件。我们的主要假设是，多巴胺神经元改变了它们对奖赏和厌恶的反应方式 刺激取决于奖励环境。更具体地说，我们假设在低回报环境下，多巴胺 神经元通过将奖赏和厌恶的值结合起来，忠实地发出价值预测错误的信号。在高 在奖赏背景下，我们假设多巴胺神经元获得对厌恶的短潜伏期兴奋性反应 刺激并降低它们对厌恶刺激的抑制反应，从而降低它们发出信号的能力 价值预测错误。目标1将检验VTA中的多巴胺神经元代表 在低回报的情况下，沿着一维价值轴的回报和厌恶的组合价值。目标2将 检验VTA多巴胺神经元在低奖赏而不是高奖赏时信号值预测错误的假设 上下文。目标3将测试这样一个假设，即对厌恶刺激的预期会减少厌恶刺激- 在低奖赏环境中，以减法方式诱导抑制。 中脑多巴胺系统的功能障碍与多种病理情况有关，包括 抑郁、快感缺乏、冷漠、精神分裂症、成瘾、饮食失调和帕金森氏症。在……里面 特别是，对显著事件的异常多巴胺反应与成瘾、精神分裂症有关 和其他精神障碍。这项研究将使我们能够更好地了解多巴胺神经元 被厌恶的事件激活，并将作为了解健康中的多巴胺信号的基础 和疾病。

Project Summary Dopamine is thought to be a key regulator of learning from appetitive as well as aversive events. It has been proposed that dopamine neurons signal value prediction error (VPE, often referred to as reward prediction error), or the difference between the values of actual and predicted outcomes. Although accumulating evidence supports this idea for reward, how dopamine neurons integrate information about aversive events remains highly controversial. Some studies have shown that aversive stimuli inhibit dopamine neurons, while others have suggested that aversive events activate at least some dopamine neurons. Others have argued that dopamine neurons largely ignore aversive events. In order to resolve the above controversy, this project aims to examine how dopamine neurons in the ventral tegmental area (VTA) convey information about aversive events . Our main hypothesis is that dopamine neurons alter the way they respond to rewarding and aversive stimuli depending on reward contexts. More specifically, we hypothesize that in low reward contexts, dopamine neurons faithfully signal value prediction errors by combining the value of both reward and aversion. In high reward contexts, we hypothesize that dopamine neurons acquire short-latency excitatory response to aversive stimuli and decrease their inhibitory responses to aversive stimuli, thereby diminishing their ability to signal value prediction errors. Aim 1 will test the specific hypothesis that dopamine neurons in VTA represent a combined value for reward and aversion along a one-dimensional value axis in a low reward context. Aim 2 will test the hypothesis that VTA dopamine neurons signal value prediction error in low but not high reward contexts. Aim 3 will test the hypothesis that expectation of an aversive stimulus reduces aversive stimulus- induced inhibition in a subtractive fashion in low reward contexts. Malfunction of the midbrain dopamine system is associated with a variety of pathological conditions including depression, anhedonia, apathy, schizophrenia, addiction, eating disorders and Parkinson's disease. In particular, aberrant dopamine responses to salient events have been implicated in addiction, schizophrenia and other mental disorders. This study will allow us to better understand situations in which dopamine neurons are activated by aversive events, and will serve as a foundation to understand dopamine signaling in health and disease.