The role of corticostriatal circuits in visually-guided behavior

皮质纹状体回路在视觉引导行为中的作用

• 批准号: 10320876
• 负责人: Andrew Moberly
• 金额: $ 6.98万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10320876
• 关键词: Address; Animals; Anterior; Architecture; Area; Auditory; Auditory area; Basal Ganglia; Basic Science; Behavior; Behavioral; Calcium; Cells; Cognition; Cognitive; Corpus striatum structure; Detection; Dorsal; Fiber; Functional disorder; Generations; Goals; Huntington Disease; Image; Individual; Link; Literature; Maps; Methodology; Methods; Modality; Modeling; Monitor; Movement; Mus; Neocortex; Neurons; Output; Parkinson Disease; Pathway interactions; Pattern; Population; Process; Role; Route; Scientist; Sensory; Stimulus; Task Performances; Testing; Training; Visual; Work; anatomical tracing; area striata; awake; base; extrastriate visual cortex; imaging system; improved; in vivo; in vivo calcium imaging; innovation; insight; motor behavior; nervous system disorder; neural circuit; novel; novel strategies; optogenetics; preservation; relating to nervous system; response; retinotopic; skills; tool; training opportunity; two-photon; visual information

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.

项目摘要 包括主要视觉区域在内的新皮层将大规模的项目发送到纹状体 被认为会影响基底神经节的活动，并最终导向目标指导的行为。尽管有链接 在基底神经节功能障碍和神经系统疾病之间，例如亨廷顿和帕金森氏病， 皮质纹状体电路的组织和功能尚不清楚。例如，在多大程度上做 新皮层转移到纹状体中的感觉图？在发送的皮质区域之间的活动如何发送 在行为过程中将输入转化为纹状体子区域？解决这些问题需要 追踪神经元电路和监测多个空间尺度的神经元活动的创新方法 在行为动物中。在这里，我利用了我们的实验室开发的几种新颖方法 在感觉引导的行为中研究视觉皮质纹状体功能。在AIM 1中，我将绘制精细尺度 将视觉输入组织到背侧纹状体。然后，我将监视皮质纹状体的活性 体内神经元以确定它们代表哪些视觉信息以及如何与大规模坐标 皮质网络，利用双重2光子和宽场介质钙成像。在AIM 2中，我会 在视觉检测中研究皮质纹状体细胞及其相关的大规模网络的活性 任务，将这些研究与光遗传操作相结合，以随便测试这些电路在 感觉引导的行为。我的结果将产生对皮质纹状体组织的基本见解 界。此外，这些研究将为我提供出色的培训机会，以扩大我的 概念和方法论技巧，支持我成为独立科学家的长期目标。