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: 6405254
• 负责人: GARY Edward PICKARD
• 金额: $ 34万
• 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/6405254
• 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征在于： 视网膜神经节细胞的巨大形态多样性， 各种中央核。这些细胞的分类揭示了， 不同的功能类别具有不同的树枝状形态，涵盖了 视网膜在独立的马赛克，并在其皮层下的目标不同。的 视交叉上核（SCN）和膝状体间叶（IGL），重要的 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 细胞尽管已知SCN和IGL的视网膜传入用于 将昼夜节律系统带入太阳日， 投射到SCN和IGL的神经节细胞的形态也没有关于 视网膜内夹带回路，对我们的昼夜节律功能至关重要， 系统为了完全理解光是如何调节我们的生物钟的，我们 我们必须了解哪些神经元将光转化为电信号，以及如何将光转化为电信号。 这些信息被集中传送到我们的昼夜节律系统。我们假设 不止一种形态学类型的神经节细胞是传入的， 昼夜节律系统 使用我们实验室开发的一种新型跨突触病毒示踪剂， PRV-152，表达增强型绿色荧光蛋白， 到SCN和IGL的视网膜输入来自于形态学上和 将测试视网膜神经节细胞的神经化学多样性群体。 将使用荧光显微镜检查视网膜神经节细胞， 荧光去卷积和电子显微镜鉴定SCN-投影 细胞离体SCN投射神经节的全细胞膜片钳记录 细胞将被进行，以确定这些细胞对光的反应 刺激.这些数据将提供有关 视网膜内夹带回路 我们生物钟的紊乱是导致 睡眠节律的不正常阶段，可能是严重的情感障碍的基础。 了解视网膜神经元和电路传入SCN和IGL将 帮助我们理解和处理这些相位干扰。