Dopaminergic modulation of nucleus accumbens during prospective and retrospective neuroeconomic decision making

前瞻性和回顾性神经经济决策过程中伏隔核的多巴胺能调节

• 批准号: 10620634
• 负责人: Adrine Kocharian
• 金额: $ 5.27万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-31 至 2026-05-14
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10620634
• 关键词: Adult; Animals; Area; Behavior; Behavioral; Biosensor; Budgets; Cells; Clinical; Collaborations; Color; Complex; Computer Analysis; Computing Methodologies; Cost Analysis; Data; Decision Making; Development; Dissociation; Dopamine; Dopamine D1 Receptor; Dopamine D2 Receptor; Economics; Evaluation; Event; Fiber; Functional disorder; Future; Goals; Human; Investments; Knowledge; Learning; Light; Literature; Measures; Mental Depression; Mental disorders; Mentors; Methods; Mind; Monitor; Motivation; Mus; Neurobiology; Neurons; Neurosciences; Neurotransmitters; Nucleus Accumbens; Obsessive-Compulsive Disorder; Opsin; Outcome; Pathology; Performance; Photometry; Physicians; Play; Population; Process; Psyche structure; Psychiatry; Research; Resolution; Restaurants; Rewards; Rodent; Role; Schizophrenia; Scientist; Signal Transduction; Sorting; System; Techniques; Time; Training; Ventral Tegmental Area; Virus; Work; behavior measurement; calcium indicator; career; collaborative environment; cost; experience; experimental study; in vivo; in vivo monitoring; information processing; innovation; neural; neural correlate; neurochemistry; neuroeconomics; neuromechanism; neuronal excitability; neuropsychiatric disorder; neuropsychiatry; neurotransmitter release; nonhuman primate; optogenetics; postsynaptic; prospective; signal processing; skills; spatiotemporal; symptomatology; tool; translational potential

PROJECT SUMMARY In 2017, it was estimated that nearly 20% of the adult population in the U.S. live with a mental illness, yet much remains unknown about the pathophysiology of psychiatric disease and the specific behavioral symptomatology. Aberrations in decision making and information processing have been implicated in neuropsychiatric diseases like schizophrenia, obsessive-compulsive disorders, and depression. Importantly, dysregulations in nucleus accumbens core (NAc core) dopamine signaling onto medium spiny neurons (MSNs) constitute a key neural mechanism underlying these aberrant processes. Currently, NAc core research disproportionately focuses on the motivation and reward-learning aspects of decision making. There is, however, strong evidence that decision making involves more complex information-processing: making a decision requires evaluation of actual outcomes but also requires prospection and retrospection on imagined alternate outcomes. Therefore, it is important to investigate the role of dopamine release and MSN activity in information processing when agents prospectively imagine potential outcomes before making a decision through deliberation and when agents retrospectively imagine what could have been in the “path untraveled” (counterfactual reasoning) or imagine poor time investments (sunk cost processing) after making a decision through reevaluation. Our understanding of how NAc core dopamine encodes these imagined outcomes during prospective deliberation and retrospective reevaluation is lacking greatly because there have not been behavioral tools with the complexity to probe the mechanisms contributing to this type of information-processing in rodents. Innovative work in the Redish lab has led to the development of a rodent behavioral task, called Restaurant Row, whose intricacy allows for in-depth behavioral analysis of neuroeconomic behaviors. This proposal aims to elucidate how NAc core dopamine dynamics reflect deliberation, counterfactual reasoning and sunk cost evaluation by 1) simultaneous monitoring of in vivo dopamine release and MSN activity using fiber photometry 2) manipulating endogenous dopamine signaling at specific points in decision making. Restaurant Row has tremendous translational potential and has been adapted for non-human primates and humans. Thus, the work proposed here will contribute to a larger translational collaboration in the future to investigate these questions across species through collaboration with my clinical mentors in the Department of Psychiatry. My advisors Dr. David Redish and Dr. Patrick Rothwell are equipped to mentor me both technically and professionally and together we have curated a training plan that perfectly aligns with my career goals. By incorporating pioneering techniques into a translational project in such an interdisciplinary environment will provide the training I need to develop become a successful physician-scientist contributing to the field of computational psychiatry.

项目摘要 在2017年，据估计，美国近20％的成年人口患有精神疾病，但很多 关于精神疾病的病理生理和特定行为症状学仍然未知。 在神经精神疾病中隐含了决策和信息处理的畸变 像精神分裂症，强迫症和抑郁症一样。重要的是， 伏隔核（NAC核）多巴胺信号传导到中刺神经元（MSN）的失调 构成这些异常过程的基础的关键神经机制。目前，NAC核心研究 不成比例地关注决策的动机和奖励学习方面。但是，有 决策涉及更复杂的信息处理的有力证据：做出决策需要 评估实际结果，但还需要对想象中的替代结果进行研究和回顾。 因此，重要的是研究多巴胺释放和MSN活性在信息处理中的作用 当代理商前瞻性地想象在通过审议和何时做出决定之前的潜在结果 回顾性的特工想象“路径不前进”（反事实推理）或 通过重新评估做出决定后，想象力不足的时间投资（沉没成本处理）。我们的 了解NAC核心多巴胺如何编码前瞻性审议期间这些想象的结果 而且缺乏回顾性重新评估，因为没有行为工具 复杂性以探测导致啮齿动物中这种信息处理的机制。创新的 在Redish Lab的工作导致了啮齿动物行为任务的发展，称为Restaurant Row，谁 复杂性允许对神经经济行为进行深入的行为分析。该建议旨在阐明 NAC核心多巴胺动态如何反映审议，反事实推理和沉没成本评估1） 同时监测体内多巴胺释放和MSN活性，使用光纤光度法2）操纵 在决策时特定点处的内源性多巴胺信号传导。餐厅行有很大的 翻译潜力，已适用于非人类隐私和人类。那是提出的工作 这将在未来进行更大的翻译合作，以调查这些问题 通过与我在精神病学系的临床导师合作的种类。我的顾问大卫博士 Redish和Patrick Rothwell博士有能力在技术上，专业和我们一起指导我 已经策划了一项完美与我的职业目标保持一致的培训计划。通过合并开拓技术 在这样的跨学科环境中进入转化项目将为我提供所需的培训 成为成功的身体科学家，为计算精神病学领域做出贡献。