Dopamine signaling and function during spatial navigation

项目摘要 多巴胺在学习和动机中起着重要作用。人们一直认为，多巴胺神经元(DAN) 信号奖励预测误差(RPE)，但最近的一些发现对这一想法提出了挑战。首先， 一些研究发现，腹侧纹状体中的多巴胺浓度随着 在目标导向导航过程中的几秒钟内，有人提出这些慢时间刻度的多巴胺 波动可能会编码价值，而不是RPE。因为RPE(由以下时间差误差定义 强化学习理论)近似是值的时间导数，这些建议是 与RPE假说不符。正如在项目1中讨论的那样，一种理论预测，增加多巴胺可以 在特定条件下由RPE解释。这个项目(项目3)将把这个想法付诸于实验测试。一个 将在头部固定的小鼠身上开发一套使用虚拟现实的实验测试(目标1)。具体地说，RPE 价值账户将通过将动物传送到与不同的 值，或通过更改场景移动的速度。目标2将检验这样的假设：一个明确的提示 这表明，在非导航环境中，奖励的接近足以诱导多巴胺的上升。 此外，通过操纵刺激参数，目标2还旨在确定在什么任务条件下 不管多巴胺有没有上升。目标3将在实验中操纵DAN的活动，并检查缓慢- 纹状体和纹状体棘突投射神经元活动调节中的多巴胺信号波动 目标导向导航中的行为。

Project abstract Dopamine plays important roles in learning and motivation. It has been thought that dopamine neurons (DANs) signal reward prediction errors (RPEs) but this idea has been challenged by some recent findings. For one, some studies found that dopamine concentration in the ventral striatum slowly ramps up on the timescale of several seconds during goal-directed navigation, and it was proposed that these slow-timescale dopamine fluctuations may encode Value instead of RPEs. Because RPEs (as defined by temporal difference error in reinforcement learning theories) are approximately the temporal derivative of Value, these proposals are incompatible with the RPE hypothesis. As discussed in Project 1, a theory predicts that ramping dopamine can be explained by RPEs in certain conditions. This project (Project 3) will put this idea into experimental tests. A set of experimental tests will be developed using virtual reality in head-fixed mice (Aim 1). Specifically, RPE and Value accounts will be dissociated by teleporting the animal to a new location associated with a different Value, or by changing the speed of the scene movement. Aim 2 will test the hypothesize that an explicit cue that indicates the proximity of reward is sufficient to induce a dopamine ramp in non-navigational contexts. Furthermore, by manipulating stimulus parameters, Aim 2 also aims at determining under what task conditions dopamine ramps or not. Aim 3 will experimentally manipulate DAN activity, and examine the function of slowly- fluctuating dopamine signals in the regulation of the activity of spiny projection neurons in the striatum and behaviors in goal-directed navigation.