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方面发挥着重要作用。人们认为多巴胺神经元（DAN） 信号奖励预测错误（RPE），但这一想法受到了最近一些发现的挑战。其一， 一些研究发现，腹侧纹状体中的多巴胺浓度在时间尺度上缓慢上升 目标导向导航过程中的几秒钟，有人提出这些慢时标多巴胺 波动可能会编码价值而不是 RPE。因为 RPE（由时间差误差定义） 强化学习理论）大约是价值的时间导数，这些建议是 与 RPE 假说不相容。正如项目 1 中所讨论的，理论预测多巴胺的增加可以 在某些条件下可以用 RPE 来解释。这个项目（项目3）将把这个想法付诸实验测试。一个 将使用虚拟现实技术在头部固定的小鼠中开发一组实验测试（目标 1）。具体来说，RPE 和价值帐户将通过将动物传送到与不同的关联的新位置来解除关联 值，或者通过改变场景移动的速度。目标 2 将测试以下假设：明确的提示 这表明奖励的接近足以在非导航环境中诱导多巴胺升高。 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 多巴胺是否增加。目标 3 将通过实验操纵 DAN 活性，并检查缓慢- 波动的多巴胺信号调节纹状体中多刺投射神经元的活动 目标导向导航中的行为。