Central mechanisms for integrating distinct retinal inputs during the optokinetic reflex in mice

小鼠视动反射过程中整合不同视网膜输入的中心机制

• 批准号: 10315952
• 负责人: Scott C Harris
• 金额: $ 3.96万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10315952
• 关键词: Algorithms; Amblyopia; Anatomy; Animals; Architecture; Automobile Driving; Axon; Behavior; Behavioral; California; Cell Nucleus; Cells; Classification; Complement; Cues; Data; Development; Diagnosis; Dorsal; Elements; Environment; Eye; Eye Movements; Goals; Head; Image; In Vitro; Interneurons; Knowledge; Label; Lateral; Life; Measures; Medial; Mentorship; Modeling; Motion; Motor; Movement; Mus; Nature; Neural Pathways; Neuraxis; Neurons; Ocular Motility Disorders; Organism; Output; Pathologic Nystagmus; Pathway interactions; Pattern; Physiology; Population; Positioning Attribute; Process; Property; Reflex action; Research Training; Resources; Retina; Retinal Ganglion Cells; Role; San Francisco; Sensory; Signal Transduction; Source; Speed; Stimulus; Strabismus; Stream; Techniques; Testing; Training; Transgenic Organisms; Translating; Universities; Vision; Visual Pathways; Whole-Cell Recordings; Work; awake; career development; cell type; extracellular; in vivo; innovation; insight; novel strategies; relating to nervous system; response; signal processing; visual information

PROJECT SUMMARY The optokinetic reflex (OKR) is an innate, visually-driven behavior that is critical to normal vision. During OKR, compensatory eye movements stabilize vision in response to slow, global image motion that often results from changes in head position. While OKR is robust across diverse species, its underlying mechanisms are unknown. This project aims to understand how distinct retinal output streams that collectively encode OKR-inducing stimuli are centrally integrated to drive eye movements. To achieve this goal, a combination of physiology and behavioral techniques will be used to measure functional readouts from three stages along the OKR pathway of the mouse in response to a common stimulus set: 1) The population activity of retinal ganglion cells that are responsible for detecting and encoding OKR-inducing stimuli, 2) Downstream neurons in the medial terminal nucleus – a primary central hub for OKR processing, and 3) The eye movements of awake animals as they perform OKR. This novel approach to describing signal transformation along the entirety of a visual pathway will provide a mapping of retinal activity onto behavior and offer insight into how and where information from distinct retinal output streams is centrally integrated. Broadly, such findings are important for revealing general strategies by which elements of the central nervous system integrate competing inputs from distinct sources. Further, revealing fundamental features of eye movement pathways will make progress towards understanding the mechanisms behind a variety of common eye movement disorders including nystagmus, strabismus, and amblyopia. This work will be complemented by a rigorous training plan that involves tailored mentorship, coursework, presentation opportunities, and career development. Along with the institutional, intellectual, and training resources available in the highly collaborative scientific environment at the University of California, San Francisco, these research and training plans will jointly facilitate the applicant’s development into an independent sensory neuroscientist.

项目摘要 视动反射（OKR）是一种先天的、视觉驱动的行为，对正常视力至关重要。在OKR期间， 补偿性眼球运动是对缓慢的、全局的图像运动的响应， 头部位置的变化。虽然OKR在不同的物种中是强大的，但其潜在机制尚不清楚。 该项目旨在了解共同编码OKR诱导刺激的不同视网膜输出流的方式 集中在一起驱动眼球运动为了实现这一目标，生理学和 行为技术将用于测量OKR途径上沿着三个阶段的功能读数 小鼠对共同刺激集的反应：1）视网膜神经节细胞的群体活性， 负责检测和编码OKR诱导的刺激，2）内侧终末的下游神经元 核-OKR处理的主要中枢，和3）清醒动物的眼球运动，因为他们 执行OKR。这种描述沿着整个视觉通路的信号变换的新方法将 提供了视网膜活动对行为的映射，并提供了对不同信息如何以及在哪里的洞察力。 视网膜输出流被集中整合。从广义上讲，这些发现对于揭示一般性战略非常重要 中枢神经系统的各个部分通过这种机制整合来自不同来源的竞争性输入。此外，本发明还 揭示眼动通路的基本特征将有助于理解 各种常见的眼球运动障碍背后的机制，包括眼球震颤，斜视， 弱视这项工作将辅之以一项严格的培训计划，其中包括有针对性的指导， 课程、演讲机会和职业发展。沿着的是制度、知识和 在旧金山的加州大学， 弗朗西斯科，这些研究和培训计划将共同促进申请人的发展成为一个独立的 感觉神经学家