Subcellular Origins of Extensive Spatial Integration by Ganglion Cell Photoreceptors

神经节细胞感光器广泛空间整合的亚细胞起源

• 批准号: 10389755
• 负责人: Franklin Caval-Holme
• 金额: $ 6.72万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10389755
• 关键词: Address; Afferent Neurons; Area; Axon; Behavior; Biophysical Process; Brain; Cells; Circadian Rhythms; Closure by clamp; Complement; Data; Dendrites; Distal; Electrophysiology (science); Exhibits; Eye; Fire - disasters; Goals; Human; Image; Investigation; Knowledge; Label; Lasers; Length; Light; Lighting; Macaca; Mammals; Measures; Mediating; Methods; Moods; Mus; Neurons; Optic Disk; Output; Patch-Clamp Techniques; Pattern; Perception; Peripheral; Photons; Photophobia; Photoreceptors; Photosensitivity; Phototransduction; Physiology; Population; Preparation; Preservation Technique; Presynaptic Terminals; Property; Proteins; Protocols documentation; Psychophysics; Publishing; Pupil; Reflex action; Regulation; Retina; Retinal Ganglion Cells; Shapes; Signal Transduction; Site; Sleep; Slice; Stimulus; Subconscious; Supporting Cell; Surface; Testing; Therapeutic; Variant; Vertebrate Photoreceptors; Vision; Visual; Visual Pathways; biophysical analysis; cellular imaging; circadian pacemaker; circadian regulation; constriction; desensitization; experimental study; ganglion cell; insight; light effects; light intensity; melanopsin; neuronal cell body; patch clamp; preservation; receptor; response; spatial integration; two-photon; voltage clamp

PROJECT SUMMARY/ABSTRACT When faced with a visual scene, the brain encodes both image detail and the scene’s overall intensity, measured as irradiance. Encoding irradiance is critical for circadian regulation, pupil constriction, and image vision, among other important functions. A canonical feature of irradiance encoding is the blurring of image detail in favor of extensive spatial integration of light. The cells in the retina that transmit irradiance information to the brain are the intrinsically photosensitive retinal ganglion cells (ipRGCs). My goal is to understand how the mechanisms of phototransduction in the ipRGCs support this spatial integration. Melanopsin, the light- sensitive protein in ipRGCs, is distributed throughout the dendrites, soma, and axon. IpRGCs send irradiance information to the brain using spikes and phototransduction within the axon is likely to shape spike output. Preliminary experiments indicate that ipRGC axons are indeed photosensitive. In mice, melanopsin immunostaining labels axons, including at the optic disk. In electrophysiological recordings of mouse ipRGCs, illumination of the axon evokes spiking responses, and the cells are more sensitive to large stimuli that illuminate their axons in addition to their somas and dendrites. I hypothesize that phototransduction in the axon enables the spatial integration of light over an unexpectedly large area. The lab has established protocols for electrophysiological recordings from the soma and axon of ipRGCs, and for imaging visually-evoked Ca2+ dynamics in the population of ipRGC axon terminals. I propose an investigation into mechanisms of axonal photosensitivity (Aim 1) and the axonal contribution to spatial integration at the level of the cell population (Aim 2). To complement my investigations in the mouse, I will also measure the properties of ipRGCs in a species that has larger eyes and thus longer axons. My proposed experiments will provide an understanding of how signal transduction operates in distinct cellular compartments of a sensory neuron to support spatial integration.

项目总结/摘要 当面对一个视觉场景时，大脑会对图像细节和场景的整体强度进行编码， 以辐照度衡量。编码辐照度对于昼夜节律调节、瞳孔收缩和成像至关重要。 视觉，以及其他重要功能。辐照度编码的一个典型特征是图像的模糊 细节有利于光线的广泛空间整合。视网膜中传递辐射信息的细胞 与大脑相连的是固有光敏视网膜神经节细胞（ipRGC）。我的目标是了解 ipRGC中的光转导机制支持这种空间整合。黑视素，光- ipRGC中的敏感蛋白分布在整个树突、索马和轴突中。IpRGC发送辐照度 使用轴突内的尖峰和光转导将信息传递到大脑可能会形成尖峰输出。 初步实验表明，ipRGC轴突确实是光敏的。在小鼠中， 免疫染色标记轴突，包括在视盘。在小鼠ipRGC的电生理记录中， 轴突的照明引起尖峰反应，并且细胞对大的刺激更敏感， 照亮它们的轴突以及胞体和树突。我假设轴突中的光传导 使得光能够在出乎意料的大面积上空间积分。实验室已经制定了 来自ipRGC的索马和轴突的电生理记录，以及用于成像视觉诱发的Ca 2 + ipRGC轴突终末群体的动态。我建议对轴突的机制进行研究 光敏性（Aim 1）和轴突在细胞群体水平上对空间整合的贡献（Aim 2）。为了补充我在小鼠中的研究，我还将测量一个物种中ipRGC的特性， 有更大的眼睛和更长的轴突。我提出的实验将提供一个理解， 信号转导在感觉神经元的不同细胞区室中起作用，以支持空间信号转导。 一体化