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 多巴胺在学习和动力中起着重要作用。人们认为多巴胺神经元（DAN） 信号奖励预测错误（RPE），但最近的一些发现挑战了这个想法。一个， 一些研究发现，腹侧纹状体中的多巴胺浓度逐渐升高 在目标导向导航期间几秒钟，有人提出这些慢速多巴胺 波动可能编码值而不是RPE。因为rpes（按时间差错误定义 强化学习理论）大约是价值的时间导数，这些建议是 与RPE假设不兼容。如项目1中所述，一个理论预测，渐变多巴胺可以 在某些条件下由RPE解释。该项目（项目3）将把这个想法投入实验测试中。一个 将使用头固定小鼠中的虚拟现实开发一组实验测试（AIM 1）。具体来说，RPE 和价值帐户将通过将动物传送到与其他不同的新位置来解离 价值，或通过改变场景运动的速度。 AIM 2将测试明确提示的假设 这表明奖励的距离足以在非杀人性情况下诱导多巴胺坡道。 此外，通过操纵刺激参数，AIM 2还旨在确定在什么任务条件下 多巴胺坡道与否。 AIM 3将通过实验操纵DAN活动，并缓慢地检查 在调节纹状体中棘投射神经元活性的调节中，多巴胺信号波动 目标定向导航中的行为。