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

基本信息

批准号：
10574483
负责人：
Franklin Caval-Holme
金额：
$ 6.95万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
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/10574483
关键词：
Address Afferent Neurons Area Axon Behavior Biophysical Process Brain Cells Circadian Rhythms Closure by clamp Compensation Complement Cone Data Dendrites Distal Electrophysiology (science)Exhibits Eye Fire - disasters Goals Human Image Investigation Knowledge Label Lasers Length Light Lighting Macaca Mammals Measures Mediating Methods Miosis disorder Moods Mus Neurons Optic Disk Output Patch-Clamp Techniques Pattern Perception Perforation 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 Rod Shapes Signal Transduction Site Sleep Slice Stimulus Subconscious Supporting Cell Surface Testing Therapeutic Variant Vision Visual Visual Pathways biophysical analysis circadian pacemaker circadian regulation constriction desensitization experimental study ganglion cell insight light effects light intensity melanopsin neuronal cell body optical disc patch clamp preservation receptor response spatial integration transmission process two-photon voltage clamp

项目摘要

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.

项目概要/摘要当面对视觉场景时，大脑会对图像细节和场景的整体强度进行编码，测量辐照度对于昼夜节律调节、瞳孔收缩和图像至关重要。视觉等重要功能之一是辐照度编码的典型特征是图像模糊。有利于光的广泛空间整合的细节。视网膜中传输辐照度信息的细胞。我的目标是了解本质上感光的视网膜神经节细胞（ipRGC）是如何影响大脑的。 ipRGC 中的光转导机制支持这种空间整合。 ipRGC 中的敏感蛋白，分布在树突、胞体和轴突中，IpRGC 发送辐照度。使用轴突内的尖峰和光转导向大脑传递的信息可能会影响尖峰输出。初步实验表明，ipRGC 轴突在小鼠中确实具有光敏性。免疫染色标记轴突，包括在小鼠 ipRGC 的电生理记录中。轴突的照明会引起尖峰反应，并且细胞对大刺激更加敏感除了体细胞和树突之外，还照亮了它们的轴突，我在轴突中的光转导方面遇到了困难。能够在意想不到的大区域内进行光的空间整合该实验室已经建立了协议。 ipRGC 体细胞和轴突的电生理记录，以及视觉诱发 Ca2+ 成像我建议对轴突的机制进行研究。光敏性（目标 1）和轴突对细胞群水平上的空间整合的贡献（目标 2). 为了补充我对小鼠的研究，我还将测量一个物种中 ipRGC 的特性。它有更大的眼睛，因此轴突更长，我提出的实验将让我们了解它是如何实现的。信号转导在感觉神经元的不同细胞区室中运行，以支持空间一体化。