Brain, Behavior and Biological Rhythms

描述（由申请人提供）：哺乳动物视网膜中的特化光感受器投射到视交叉上核（SCN）的昼夜节律钟。这些光感受器含有黑视蛋白。关于含有黑视素的视网膜神经节细胞投射到SCN的独特性产生了问题。来自视网膜神经节细胞的轴突侧支支配SCN和至少一个其他视觉核。分叉神经节细胞含有黑视素的程度将被解决。这些结果对调节昼夜节律系统的时间整合和光敏感能力的解剖学基质的功能研究具有影响。功能实验旨在评估视觉通路中各个部分在评估昼夜节律系统对光反应中所起的作用。药物和损伤实验将以顺序的方式确定瞳孔、视网膜、SCN或IGL是否有助于仓鼠昼夜节律系统的能力，以有效地评估刺激亮度或提供随时间的刺激整合，并在SCN神经元的核中产生节律相移或FOS蛋白的诱导。例如，动物将接受单侧视网膜封堵器并进行测试以确定向昼夜节律钟提供信息的光感受器的50%的功能丧失是否会改变相移或FOS对光响应的幅度。其他实验将确定SCN或IGL是否对这些响应有贡献。研究后一个核的部分逻辑依赖于IGL控制大约50%的昼夜节律周期对恒定光照的反应。因此，可能是IGL介导了光的紧张效应（光子在时间上的总和？），而SCN介导光对昼夜节律系统的相位效应。对视网膜的研究针对含有黑视素的视网膜神经节细胞的功能。这些问题将使用双道追踪和靶向免疫毒素方法进行研究。该项目的总体目标是进一步阐明视觉系统对光的昼夜节律反应的调节的贡献，特别强调相位控制。

DESCRIPTION (provided by applicant): Specialized photoreceptors in the mammalian retina project to the circadian clock of the suprachiasmatic nucleus (SCN). These photoreceptors contain melanopsin. Questions arise regarding the uniqueness of the melanopsin-containing retinal ganglion cell projections to the SCN. Axon collaterals from retinal ganglion cells innervate both the SCN and at least one other visual nucleus. The extent to which the bifurcating ganglion cells contain melanopsin will be addressed. These results have ramifications for the functional studies of the anatomical substrate mediating the temporal integration and photic sensitivity capacity of the circadian rhythm system. Functional experiments are designed to evaluate the role played by various parts in the visual pathway in assessing circadian rhythm system response to light. Drug and lesion experiments will, in sequential fashion, determine whether the pupil, retina, SCN or IGL contribute to the capacity of the hamster circadian rhythm system to effectively assess stimulus brightness or provide stimulus integration over time and generate a rhythm phase shift or induction of FOS protein in nuclei of SCN neurons. For example, animals will receive a unilateral retinal occluder and tested to determine whether functional loss of 50% of the photoreceptors providing information to the circadian clock will modify the magnitude of the phase shift or FOS response to light. Other experiments will determine whether there is a contribution to these responses being made by the SCN or IGL. Part of the logic for studying the latter nucleus rests on the fact that the IGL controls approximately 50% of the circadian period response to constant light. Thus, it may be that the IGL mediates the tonic effects of light (summation of photons across time?), whereas the SCN mediates the phasic effects of light, on the circadian rhythm system. Studies of the retina are directed at the function of the melanopsin-containing retinal ganglion cells. These issues will be studied using dual tract tracing and targeted immunotoxin methods. The overall goal of the project is to further elucidate the contribution of the visual system to the regulation of circadian rhythm response to light with particular emphasis on phase control.