Retinal Neurons Afferent to the Circadian System

描述(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形态多样性很大，这些细胞将轴突发送到 中央核种类繁多。对这些细胞的分类表明 不同的功能类具有不同的树枝状形态，包括 视网膜中的独立马赛克，并在其皮质下的目标不同。这个 视交叉上核(SCN)和膝间叶(IGL)，重要 哺乳动物昼夜节律系统的组成部分，是视网膜神经节的靶标 细胞。尽管已知SCN和IGL的视网膜传入起着 将昼夜节律系统引入太阳日，人们对此几乎一无所知 投射到SCN和IGL的神经节细胞的形态 视网膜内夹带回路，对我们昼夜节律的功能至关重要 系统。为了完全了解光是如何调节我们的生物钟的，我们 必须了解哪些神经元将光转换为电信号以及如何 这些信息被集中传递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，假设 视网膜对SCN和IGL的输入来自于形态和 将测试具有神经化学多样性的视网膜神经节细胞群。 视网膜神经节细胞将用荧光显微镜和 识别的SCN投射的荧光去卷积和电子显微镜 细胞。体外全细胞膜片钳记录SCN投射神经节 将进行细胞培养，以确定这些细胞对光的反应 刺激。这些数据将提供有关 视网膜内缠绕回路。 我们生物钟携带过程中的干扰是 睡眠节律不正常，可能导致严重的情感障碍。 了解SCN和IGL的视网膜神经元和传入回路将 帮助我们理解和处理这些相位的干扰。

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.