Bidirectional Interactions of Cortex and Basal Ganglia During Action Selection

项目摘要/摘要 根据以前的经验选择未来的行动是动物生存的关键。这一过程称为 动作的选择，取决于皮质和皮质下基底节回路的正常功能。尽管 这些地区对于利用以前的经验为即将到来的汽车选择提供信息的重要性，我们没有 了解这些区域协同工作的确切机制以及它们使用的活动模式 选择操作。这些区域在动作选择中的意义在皮质引起的障碍中是显而易见的 和基底节功能障碍。一种假设是大脑皮层发展运动计划，而基底节 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节 在大脑中形成一个循环的环路，然而我们不知道这两者是如何共同促进和 选择操作。这种知识上的差距部分是由于我们缺乏评估和扰乱大脑皮层和 同时还有基底节。在这项建议中，我将通过研究经常性的 在正在进行的作用中，大脑皮质和基底神经节之间的相互作用。我将重点放在鼠标上 前外侧运动皮质(ALM)和纹状体是基底节的主要输入核。我的 最重要的假设是，纹状体的活动是基于动作结果及其对 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中实施双光子钙成像，在纹状体中进行大规模电生理，特定部位 纹状体干扰，以及一个利用过去信息产生未来动作的双选项运动任务。在这 提案中，我将确定1)在动作选择过程中，纹状体活动如何影响ALM中的运动规划，以及 2)如果纹状体活动是正确动作所必需的，则在动作选择期间更新ALM中的纹状体活动。总而言之，这些目标 将告诉我们大脑皮层和纹状体回路如何动态地相互作用来产生持续的行为。我的研究目标 目的是研究纹状体和皮质参与动作选择的基本机制。我的 学术目标是在计算神经科学方面建立坚实的基础，并继续改进 在此奖学金结束时，我将需要职业发展技能来过渡到独立。的实验室 我的赞助人贝尔纳多·萨巴蒂尼博士和哈佛医学院社区将提供出色的培训 为这次联谊创造了良好的环境。萨巴蒂尼博士是基底节生理学、双光子成像、 以及对神经数据的分析。萨巴蒂尼实验室和哈佛医学院神经生物学系 将为神经生物学培训提供优秀的职业发展资源，重点放在 合作与科技创新。

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.