Subcellular Origins of Extensive Spatial Integration by Ganglion Cell Photoreceptors

项目摘要/摘要 当面对视觉场景时，大脑同时编码图像细节和场景的整体强度， 以辐照度测量。对辐照度进行编码对于昼夜节律、瞳孔收缩和图像至关重要 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 细节有利于光的广泛空间整合。视网膜中传递辐射信息的细胞 对大脑来说是天生的光敏性视网膜神经节细胞(IpRGC)。我的目标是了解 IpRGCs中的光传导机制支持这种空间整合。黑色素，光- 在ipRGCs中，敏感蛋白分布于树突、胞体和轴突。IpRGC发送辐照度 通过轴突内的尖峰和光传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轴突确实是光敏的。在小鼠中，黑素 免疫染色标记轴突，包括视盘。在小鼠ipRGC的电生理记录中， 照亮轴突会引起尖峰反应，细胞对大的刺激更敏感 除了胞体和树突外，还能照亮它们的轴突。我假设轴突中的光传导 在意想不到的大范围内实现光的空间集成。实验室已经制定了用于 IpRGC胞体和轴突的电生理记录及视觉诱发的钙离子成像 IpRGC轴突终末的种群动态。我建议对轴突的机制进行研究。 光敏性(目标1)和轴突对细胞群体水平的空间整合的贡献(目标1) 2)。为了补充我在小鼠身上的研究，我还将测量一个物种中ipRGC的特性 它们有更大的眼睛，因此轴突也更长。我提议的实验将提供一个了解如何 信号转导在感觉神经元的不同细胞隔间运行，以支持空间 整合。

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.