Bidirectional Interactions of Cortex and Basal Ganglia During Action Selection

动作选择过程中皮层和基底神经节的双向相互作用

• 批准号: 10265465
• 负责人: Allison Elizabeth Girasole
• 金额: $ 7.14万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2023-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10265465
• 关键词: Address; Anatomy; Animals; Anterior; Basal Ganglia; Behavior; Brain; Calcium; Cells; Collaborations; Communities; Corpus striatum structure; Data; Decision Making; Disease; Electrophysiology (science); Environment; Feedback; Fellowship; Foundations; Functional disorder; Future; Goals; Head; Huntington Disease; Image; Knowledge; Laboratories; Lateral; Modification; Monitor; Motor; Motor Cortex; Motor output; Movement; Mus; Neurobiology; Neurons; Outcome; Output; Parkinson Disease; Pathway interactions; Pattern; Physiology; Process; Publishing; Ramp; Recording of previous events; Recurrence; Research; Resource Development; Rewards; Rodent; Selectins; Signal Transduction; Site; Structure; Technology; Testing; Training; Update; Work; awake; base; career development; computational neuroscience; density; experience; experimental study; extracellular; improved; innovation; insight; medical schools; novel; optogenetics; outcome prediction; programs; relating to nervous system; skill acquisition; tool; two photon microscopy; two-photon

Project Summary/Abstract Selecting future actions based on previous experiences is key to an animal's survival. This process, known as action selection, depends on the proper function of cortical and subcortical basal ganglia circuits. Despite the importance of these regions for using previous experiences to inform upcoming motor choices, we do not understand the precise mechanisms by which these regions work together and the activity patterns they use to select actions. The significance of these regions in action selection is clear in disorders that arise from cortical and basal ganglia dysfunction. One hypothesis is that the cortex develops motor plans that the basal ganglia then executes and evalulates based on outcome. Based on anatomy, we know that cortex and basal ganglia form a recurrent loop in the brain, however we do not understand how the two work together to promote and select actions. This gap in knowledge is due in part to our lack of technology to assess and perturb cortex and basal ganglia simultaneously. In this proposal, I will overcome these limitations by examining the recurrent interactions between the cortex and basal ganglia during ongoing action selectin. I will focus on the mouse anterior lateral motor cortex (ALM) and the striatum, the primary input nucleus of the basal ganglia. My overarching hypothesis that striatal activity is modified based on action outcome and its recurrent feedback to ALM is necessary to update subsequent motor planning required for action selection. To test my hypothesis, I plan to implement 2-photon calcium imaging in ALM, large-scale electrophysiology in striatum, site-specific striatal perturbations, and a two-choice motor task which uses past information to produce future actions. In this proposal, I will determine 1) how striatal activity influences motor planning in ALM during action selection, and 2) if striatal activity is necessary for proper action updating in ALM during action selection. Together, these aims will tell us how cortical and striatal circuits dynamically interact to produce ongoing behavior. My research goals are to investigate the fundamental mechanisms by which striatum and cortex contribute to action selection. My academic goals are to build a strong foundation in computational neuroscience and continue to improve the career development skills I will need for my transition to independence at the end of this fellowship. The lab of my sponsor, Dr. Bernardo Sabatini, and the Harvard Medical School community will provide an excellent training environment for this fellowship. Dr. Sabatini is a leading expert in basal ganglia physiology, 2-photon imaging, and the analysis of neural data. The Sabatini lab and the Department of Neurobiology at Harvard Medical School will provide excellent career development resources for training in neurobiology with a strong focus on collaboration and scientific innovation.

项目概要/摘要 根据以前的经验选择未来的行动是动物生存的关键。这个过程，称为 动作选择取决于皮质和皮质下基底神经节回路的适当功能。尽管 这些区域对于利用以前的经验来指导即将进行的电机选择的重要性，我们不 了解这些区域协同工作的精确机制以及它们用来实现目标的活动模式 选择操作。在皮质引起的疾病中，这些区域在动作选择中的重要性是显而易见的。 和基底神经节功能障碍。一种假设是皮层制定了基底神经节的运动计划 然后根据结果执行和评估。根据解剖学，我们知道皮质和基底神经节 在大脑中形成一个循环回路，但是我们不明白两者如何共同作用来促进和 选择操作。这种知识差距的部分原因是我们缺乏评估和扰乱大脑皮层和大脑皮层的技术。 基底节同时。在本提案中，我将通过检查经常性的问题来克服这些限制 在持续的动作选择过程中皮层和基底神经节之间的相互作用。我将专注于鼠标 前外侧运动皮层（ALM）和纹状体，基底神经节的主要输入核。我的 总体假设是纹状体活动根据行动结果及其反复反馈进行修改 ALM 对于更新动作选择所需的后续电机规划是必要的。为了检验我的假设，我 计划在ALM、纹状体大规模电生理学、位点特异性中实施2光子钙成像 纹状体扰动，以及利用过去的信息产生未来行动的二选一运动任务。在这个 建议，我将确定 1）纹状体活动在动作选择期间如何影响 ALM 中的运动规划，以及 2) 在动作选择期间，纹状体活动是否对于 ALM 中正确的动作更新是必要的。这些目标共同实现 将告诉我们皮质和纹状体电路如何动态相互作用以产生持续的行为。我的研究目标 旨在研究纹状体和皮层促进动作选择的基本机制。我的 学术目标是为计算神经科学奠定坚实的基础，并继续改进 在本次奖学金结束后，我将需要职业发展技能来过渡到独立。的实验室 我的赞助商 Bernardo Sabatini 博士和哈佛医学院社区将提供出色的培训 本次联谊的环境。 Sabatini 博士是基底神经节生理学、2 光子成像、 以及神经数据的分析。哈佛医学院萨巴蒂尼实验室和神经生物学系 将为神经生物学培训提供优秀的职业发展资源，重点关注 协作和科学创新。