Activity-Dependent Tagging of Cerebellar Neurons for Studying Signal Processing and Learning

用于研究信号处理和学习的小脑神经元活动依赖性标记

• 批准号: 10319181
• 负责人: Jennifer L Raymond
• 金额: $ 19.22万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10319181
• 关键词: Architecture; Area; Behavior; Behavior Control; Behavioral; Brain; Calcium; Calcium Signaling; Cells; Cerebellar Cortex; Cerebellar Diseases; Cerebellum; Code; Computer Analysis; Corpus striatum structure; Cytosol; Disease; Electrophysiology (science); Eye Movements; Fiber; Genes; Goals; Golgi Apparatus; Histology; Hour; Image; Individual; Intervention; Laboratories; Learning; Learning Skill; Light; Lighting; Methods; Modernization; Modification; Molecular; Motor; Motor Pathways; Myoepithelial cell; Neurons; Neurosciences; Opsin; Outcome; Pathway interactions; Performance; Photometry; Play; Property; Prosencephalon; Purkinje Cells; Research; Resistance; Role; Sensory; Signal Pathway; Signal Transduction; Specificity; System; Techniques; Vision; Visual; Work; base; cognitive function; combinatorial; comparative efficacy; computer studies; efficacy evaluation; granule cell; improved; in vivo; inhibitory neuron; insight; interest; motor learning; motor skill learning; neural circuit; novel strategies; oculomotor; oculomotor behavior; optogenetics; population based; ratiometric; recruit; relating to nervous system; response; signal processing; stellate cell; temporal measurement; tool; vestibulo-ocular reflex; visual motor; visual-vestibular

PROJECT SUMMARY The goal of the proposed research is to implement state-of-the-art techniques for recording and manipulating neurons based on their activity in the cerebellum, to dissect the computations performed by the cerebellum to control eye movements. Vision is an active sense, and the accurate control of eye movements plays an essential role in vision. The cerebellum plays a key role in the control of eye movements, and in the refinement of eye movement accuracy and precision through oculomotor learning. It is known that the part of the cerebellum controlling eye movements receives visual and vestibular sensory information as well as copies of the eye movement commands, and presumably uses these sensory and motor signals to guide oculomotor performance and its modification by learning. However, a number of technical challenges have limited our ability to study how different sensory and motor signals are integrated in the cerebellum, and how the different signaling pathways are each modified during learning to improve oculomotor performance. Two newly developed tools, CaMPARI and Cal-Light, hold great promise to overcome some of the technical challenges that have limited studies of cerebellar computation. These tools offer advanced precision in the ability to record and manipulate neurons based on their activity during specific task conditions. We will (1) evaluate the efficacy of CAMPARI and Cal-light for selectively targeting (“tagging”), subpopulations of cerebellar neurons in a task- and activity-dependent manner, and (2) use these tools to dissect the computations implemented by the cerebellum during oculomotor performance and oculomotor skill learning. The technical outcome of the proposed work will be a new set of experimental approaches for studying the cerebellum, as well as new experimental strategies for studying computation and learning in other neural circuits. The scientific outcome will be new insights about the computations performed by the cerebellum on its sensory (visual and vestibular) and motor (efference copy) inputs. Advances in understanding how the cerebellum supports accurate eye movements will provide conceptual underpinning for developing more rational interventions for oculomotor disorders, and, more generally for the wide array of disorders associated with cerebellar dysfunction.

项目概要 拟议研究的目标是实施最先进的记录和操作技术 基于小脑中神经元的活动，剖析小脑执行的计算 视觉是一种主动的感觉，对眼球运动的精确控制至关重要。 小脑在控制眼球运动和眼睛的精细化方面起着关键作用。 众所周知，通过动眼神经学习来提高运动的准确性和精确性。 控制眼球运动接收视觉和前庭感觉信息以及眼睛的副本 运动命令，并可能使用这些感觉和运动信号来指导动眼神经性能 以及通过学习对其进行修改。然而，许多技术挑战限制了我们研究如何进行的能力。 不同的感觉和运动信号在小脑中整合，以及不同的信号通路如何整合 两个新开发的工具 CaMPARI 在学习过程中进行了修改，以提高动眼能力。 和 Cal-Light，有望克服一些研究有限的技术挑战 这些工具在记录和操纵神经元的能力方面提供了先进的精度。 根据他们在特定任务条件下的活动，我们将 (1) 评估 Campari 和 Cal-light 的功效。 用于选择性地靶向（“标记”）任务和活动依赖性的小脑神经元亚群 方式，以及（2）使用这些工具来剖析小脑在动眼神经期间实现的计算 拟议工作的技术成果将是一套新的表现和动眼技能学习。 研究小脑的实验方法以及新的实验策略 其他神经回路的计算和学习的科学成果将是关于神经回路的新见解。 小脑对其感觉（视觉和前庭）和运动（参考副本）进行的计算 了解小脑如何支持准确的眼球运动的进展将提供输入。 为动眼神经疾病制定更合理的干预措施的概念基础，以及更多 通常用于与小脑功能障碍相关的多种疾病。