Neural circuit regulation of ramping activity in dopamine neurons

项目摘要 当啮齿动物导航到空间遥远的奖赏时，腹侧纹状体多巴胺逐渐上升，这令人惊讶 多巴胺功能的时间差分学习模型没有预料到的最新发现。坡道 腹侧纹状体的多巴胺释放反映了目标的价值和接近程度，根据目标的价值来衡量 在不同的环境中进行奖励和拉伸或压缩，以跨越起点和目标之间的距离 地点。当动物靠近时，腹侧被盖区(VTA)的多巴胺神经元的活动也会增强 目标，但多巴胺神经元起伏活动的强度和持久性取决于 目标接近的内部模型和任务经验的数量。多巴胺神经元的升压活动 当幼稚的老鼠在空间环境中跑向新发现的奖励时，立即出现 如果关于奖励接近的感觉信息在几天的训练中逐渐消失，斜坡就会逐渐消失 可用。然而，当需要实现目标的进度的内部表示时，稳健的坡度 多巴胺神经元的活动会无限期地持续下去。这些发现表明，坡度活动的假说 在VTA中，多巴胺神经元依赖于代表大脑内部模型的大脑区域的使用 环境和当前实现目标的进展情况。我们建议通过解决以下问题来检验这一总体假设 具体目标如下：1)检验腹侧海马区神经活动有助于 中脑多巴胺神经元的斜坡活动。2)比较VTA多巴胺的斜坡活性的演变 腹侧纹状体多巴胺释放随时间变化的神经元。3)表征神经活动 在VTA中，GABA神经元在空间和非空间导航过程中获得奖赏。了解神经 多巴胺神经元斜坡活动的基础机制将与以下神经基础相关 认知控制、目标导向行为、毅力和空间学习。我们的发现将提供有价值的 与这些能力障碍相关的精神障碍的相关信息，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.