Dopamine signaling and function during spatial navigation

空间导航过程中的多巴胺信号传导和功能

• 批准号: 10687833
• 负责人: Naoshige Uchida
• 金额: $ 43.8万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10687833
• 关键词: Affect; Anatomy; Animals; Area; Auditory; Behavior; Behavioral; Corpus striatum structure; Cues; Data; Dissociation; Dopamine; Dorsal; Exhibits; Formulation; Future; Goals; Head; Learning; Location; Locomotion; Machine Learning; Measures; Mediating; Modeling; Motivation; Motor; Motor Activity; Movement; Mus; Neurons; Play; Psychological reinforcement; Ramp; Regulation; Rewards; Role; Sensory; Signal Transduction; Speed; Stimulus; Substantia nigra structure; Sum; System; Testing; Time; Uncertainty; Update; Ventral Striatum; Ventral Tegmental Area; Visual; Work; computer framework; dopaminergic neuron; expectation; experience; experimental study; neurotransmission; optogenetics; pars compacta; rate of change; restraint; theories; virtual; virtual reality; virtual reality system; visual stimulus; way finding

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.

项目摘要 多巴胺在学习和动机中起着重要作用。多巴胺神经元（DAN） 信号奖励预测错误（RPE），但这一想法受到了一些最近的发现的挑战。首先， 一些研究发现，腹侧纹状体中的多巴胺浓度在一段时间内缓慢上升， 在目标导向的导航过程中几秒钟，有人提出，这些慢时间尺度的多巴胺 波动可以编码值而不是RPE。因为RPE（如由时间差误差定义的， 强化学习理论）近似于值的时间导数，这些建议是 与RPE假说不一致。正如项目1中所讨论的，一种理论预测，多巴胺的增加可以 在某些情况下可以用RPE来解释。这个项目（项目3）将把这个想法付诸实验测试。一 将在头部固定的小鼠中使用虚拟现实开发一组实验测试（目标1）。具体来说，RPE 和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将测试一个假设，即一个明确的线索 这表明奖励的接近足以在非导航环境中诱导多巴胺斜坡。 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， 多巴胺是否上升目的3将实验性地操纵DAN活性，并检查缓慢- 波动的多巴胺信号在纹状体多刺投射神经元活动的调节中， 目标导向导航中的行为。