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: 6609641
• 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/6609641
• 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是 视网膜神经节细胞的巨大形态学多样性将轴突发送到一个 中央核的种类。这些细胞的分类表明 不同的功能类具有不同的树突形态，覆盖 视网膜在独立的马赛克中，并在皮层下靶标不同。这 近手术核（SCN）和互卵形小叶（IGL），重要 哺乳动物昼夜节律的组成部分是视网膜神经节的靶标 细胞。尽管众所周知，SCN和IGL的视网膜传入用于 将昼夜节系统纳入太阳日，几乎一无所知 向SCN和IGL投射的神经节细胞的形态 视网膜内夹带电路，对于昼夜节律的功能至关重要 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换为电信号，以及 这些信息集中在我们的昼夜节律系统中。我们假设 多种形态类型的神经节细胞与 昼夜节律系统。 使用在我们的实验室中开发的新型透射性病毒示踪剂， PRV-152，表达增强的绿色荧光蛋白，这一假设是 对SCN和IgL的视网膜输入来自形态学和 将测试神经化学上不同的视网膜神经节细胞种群。 视网膜神经节细胞将使用荧光光学显微镜检查和 已鉴定的SCN射击的荧光反卷积和电子显微镜 细胞。 SCN预测神经节的体外全细胞贴片钳记录 将进行细胞以确定这些细胞对光的响应 刺激。这些数据将提供有关该数据的宝贵新信息 视网膜内夹带电路。 我们生物钟的夹带的干扰是负责的 睡眠节奏的异常阶段和可能是严重情感障碍的基础。 了解SCN和IGL传播的视网膜神经元和电路将会 帮助我们理解和治疗这些相障碍的能力。