Neural circuit regulation of ramping activity in dopamine neurons

项目摘要 当啮齿动物向空间上遥远的奖励导航时，纹状体多巴胺逐渐升高，这是一个令人惊讶的结果。 最近的发现是没有预期的时间差异学习模型的多巴胺功能。斜变 腹侧纹状体的多巴胺释放反映了目标的价值和接近程度， 奖励和拉伸或压缩在不同的环境，以跨越之间的距离开始和目标 地点腹侧被盖区（VTA）多巴胺神经元的活动也随着动物的接近而增加 目标，但多巴胺神经元中斜坡活动的强度和持久性取决于使用 目标接近度的内部模型和任务经验的量。多巴胺神经元的斜坡活动 当天真的老鼠在空间环境中跑向新发现的奖励时， 如果关于奖励接近度的感觉信息被 available.然而，当需要实现目标的进度的内部表示时， 多巴胺神经元的活动无限期地持续。这些发现提出了一个假设， 在腹侧被盖区多巴胺神经元依赖于大脑区域的使用，这些区域代表了大脑的内部模型。 环境和当前的目标进展。我们建议通过解决以下问题来测试这一总体假设： 具体目标如下：1）验证腹侧海马神经活动有助于 中脑多巴胺神经元的活性增加。2)比较腹侧被盖区多巴胺 神经元与腹侧纹状体中多巴胺释放斜坡的进化。3)表征神经活动 在VTA GABA神经元在空间和非空间导航的奖励。了解神经 多巴胺神经元中斜坡活动的基础机制将与多巴胺神经元的神经基础相关。 认知控制、目标导向行为、毅力和空间学习。我们的发现将提供宝贵的 与这些能力功能障碍相关的精神障碍相关的信息，包括注意力缺陷 多动症、强迫症、抑郁症和成瘾。

Project Summary Ventral striatal dopamine progressively rises as rodents navigate toward spatially distant rewards, a surprising recent finding that was not anticipated by temporal difference learning models of dopamine function. Ramping dopamine release in the ventral striatum reflects the value and proximity of goals, scaling by the value of the reward and stretching or compressing in different environments to span the distance between start and goal locations. Activity in ventral tegmental area (VTA) dopamine neurons also ramps up as animals approach goals, but the strength and persistence of ramping activity in dopamine neurons depends on both the use of an internal model of goal proximity and on the amount of task experience. Ramping activity in dopamine neurons appears immediately when naïve mice run toward newly-discovered rewards in spatial environments, and ramps gradually fade away over several days of training if sensory information about reward proximity is available. When an internal representation of progress toward the goal is required, however, robust ramping activity in dopamine neurons persists indefinitely. These findings suggest the hypothesis that ramping activity in VTA dopamine neurons depends on the use of brain regions that represent an internal model of the environment and current progress toward goals. We propose to test this overarching hypothesis by addressing the following specific aims: 1) Test the hypothesis that neural activity in the ventral hippocampus contributes to ramping activity in midbrain dopamine neurons. 2) Compare the evolution of ramping activity in VTA dopamine neurons with the evolution of ramping dopamine release in the ventral striatum. 3) Characterize neural activity in VTA GABA neurons during spatial and non-spatial navigation to rewards. Understanding the neural mechanisms that underlie ramping activity in dopamine neurons will have relevance for the neural basis of cognitive control, goal-directed behavior, perseverance, and spatial learning. Our findings will provide valuable information relevant for mental disorders associated with dysfunction in these abilities including attention deficit hyperactivity disorder, obsessive compulsive disorder, depression, and addiction.