The role of corticostriatal circuits in visually-guided behavior

项目摘要 新皮层，包括初级视觉区，向纹状体发送大量的投射， 被认为影响基底神经节的活动，并最终影响目标导向的行为。尽管联系 基底神经节功能障碍和神经系统疾病如亨廷顿氏病和帕金森氏病之间的联系， 皮质纹状体回路的组织和功能还不清楚。例如，在多大程度上 新皮层的感觉地图转移到纹状体大脑皮层区域之间的活动 在行为过程中协调纹状体亚区的输入？解决这些问题需要 在多个空间尺度上追踪神经回路和监测神经元活动的创新方法 动物的行为。在这里，我利用我们实验室开发的几种新方法， 研究感觉引导行为中视觉皮质纹状体功能。在目标1中，我将绘制 背内侧纹状体视觉输入的组织。然后我会监测皮质纹状体的活动 神经元在体内，以确定他们代表什么视觉信息，以及他们如何协调与大规模的 皮质网络，利用双2光子和宽场介观钙成像。在目标2中，我将 在视觉检测中研究皮质纹状体细胞及其相关大规模网络的活动 任务，将这些研究与光遗传学操作相结合，因果地测试这些电路在 感官引导的行为我的研究结果将产生对皮质纹状体组织的基本见解。 电路.此外，这些研究将为我提供一个出色的培训机会，以扩大我的 概念和方法技能，支持我成为独立科学家的长期目标。

PROJECT SUMMARY The neocortex, including primary visual areas, sends massive projections to the striatum where they are thought to influence activity in the basal ganglia and, ultimately, goal-directed behavior. Despite the link between basal ganglia dysfunction and neurological disorders such as Huntington’s and Parkinson’s disease, the organization and function of corticostriatal circuits is not well understood. For example, to what extent do sensory maps in the neocortex transfer to the striatum? How is activity between cortical areas that send converging inputs to striatal subregions coordinated during behavior? Addressing these questions requires innovative approaches to tracing neural circuits and monitoring neuronal activity across multiple spatial scales in behaving animals. Here, I take advantage of several novel methodologies developed by our labs to investigate visual corticostriatal function in sensory-guided behavior. In Aim 1, I will map the fine-scale organization of visual inputs to the dorsomedial striatum. I will then monitor the activity of corticostriatal neurons in vivo to determine what visual information they represent and how they coordinate with large-scale cortical networks, making use of dual 2-photon and wide-field mesoscopic calcium imaging. In Aim 2, I will investigate the activity of corticostriatal cells and their associated large-scale networks in a visual detection task, combining these studies with optogenetic manipulations to causally test the role of these circuits in sensory-guided behavior. My results will generate fundamental insights into the organization of corticostriatal circuits. Moreover, these studies will provide me with an outstanding training opportunity to broaden my conceptual and methodological skills, supporting my long-term goal to become an independent scientist.