Retinal Neurons Afferent to the Circadian System

传入昼夜节律系统的视网膜神经元

• 批准号: 6539179
• 负责人: GARY Edward PICKARD
• 金额: $ 32.63万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6539179
• 关键词: afferent nerve; circadian rhythms; electrodes; electron microscopy; fluorescence microscopy; genetically modified animals; green fluorescent proteins; hamsters; immunocytochemistry; in situ hybridization; laboratory mouse; lateral geniculate body; light adaptations; medial geniculate body; neurochemistry; photobiology; retinal bipolar neuron; retinal ganglion; suprachiasmatic nucleus; transfection /expression vector; visual pathways; visual photoreceptor; visual stimulus; voltage /patch clamp

DESCRIPTION (provided by applicant): Mammalian retinas are characterized by the great morphological diversity of retinal ganglion cells that send axons to a variety of central nuclei. Classification of these cells has revealed that different functional classes have distinct dendritic morphologies, cover the retina in independent mosaics, and vary in their subcortical targets. The suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL), important components of the mammalian circadian system, are targets of retinal ganglion cells. Although it is known that retinal afferents to the SCN and IGL serve to entrain the circadian system to the solar day, virtually nothing is known about the morphology of ganglion cells that project to the SCN and IGL nor about the intra-retinal entrainment circuit, critical to the functioning of our circadian system. To understand completely how light regulates our biological clock, we must understand which neurons convert light into an electrical signal and how this information is conveyed centrally to our circadian system. We hypothesize that more than a single morphological type of ganglion cell is afferent to the circadian system. Using a novel transsynaptic viral tracer developed in our laboratories, PRV-152, expressing enhanced green fluorescent protein, the hypothesis that retinal input to the SCN and IGL arises from a morphologically and neurochemically diverse population of retinal ganglion cells will be tested. Retinal ganglion cells will be examined using fluorescence light microscopy and fluorescence deconvolution and electron microscopy of identified SCN-projecting cells. In vitro whole-cell patch-clamp recording of SCN-projecting ganglion cells will be conducted to determine the responses of these cells to light stimulation. These data will provide valuable new information regarding the intraretinal entrainment circuit. Disturbances in the entrainment of our biological clock are responsible for abnormal phasing of sleep rhythms and may underlie serious affective disorders. Understanding the retinal neurons and circuits afferent to the SCN and IGL will aid in our ability to understand and treat these disturbances of phase.

描述（由申请人提供）：哺乳动物视网膜的特点是 将轴突发送到视网膜的视网膜神经节细胞具有巨大的形态多样性 各种中心核。这些细胞的分类表明 不同的功能类别具有不同的树突形态，涵盖 视网膜处于独立的马赛克状态，并且其皮层下目标各不相同。这 视交叉上核 (SCN) 和膝间小叶 (IGL)，重要 哺乳动物昼夜节律系统的组成部分，是视网膜神经节的目标 细胞。尽管众所周知，视网膜传入 SCN 和 IGL 的作用是 将昼夜节律系统引入太阳日，对此几乎一无所知 投射到 SCN 和 IGL 的神经节细胞的形态，也不涉及 视网膜内夹带回路，对我们的昼夜节律功能至关重要 系统。为了完全了解光如何调节我们的生物钟，我们 必须了解哪些神经元将光转化为电信号以及如何 这些信息集中传送到我们的昼夜节律系统。我们假设 不止一种形态类型的神经节细胞传入 昼夜节律系统。 使用我们实验室开发的新型突触病毒示踪剂， PRV-152，表达增强型绿色荧光蛋白，假设 视网膜对 SCN 和 IGL 的输入源自形态学和 将测试神经化学多样性的视网膜神经节细胞群。 将使用荧光显微镜检查视网膜神经节细胞并 已识别的 SCN 投影的荧光解卷积和电子显微镜 细胞。 SCN投射神经节的体外全细胞膜片钳记录 将进行细胞测定，以确定这些细胞对光的反应 刺激。这些数据将提供有关 视网膜内夹带电路。 我们生物钟的紊乱是导致 睡眠节律的异常阶段可能是严重情感障碍的基础。 了解传入 SCN 和 IGL 的视网膜神经元和回路将 帮助我们理解和治疗这些相位紊乱的能力。