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: 10460157
• 负责人: Naoshige Uchida
• 金额: $ 43.78万
• 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/10460157
• 关键词: Affect; Anatomy; Animals; Area; Auditory; Behavior; Behavioral; Corpus striatum structure; Cues; Data; Dopamine; Dorsal; Exhibits; Formulation; Future; Goals; Head; Lead; 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; base; computer framework; dopaminergic neuron; expectation; experience; experimental study; optogenetics; pars compacta; rate of change; 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