ipRGC participation and modulation of retinal wave activity

描述(由申请人提供)： 视网膜波包括在未成熟的视网膜上传播的自发激活区。这些波被认为参与了视网膜定位图的形成和双眼输入到上丘和外侧膝状核的分离。视网膜波发生在视杆细胞和视锥细胞感光细胞成熟之前，而此时视网膜被认为对光不敏感。然而，最近的发现证明这一假设是无效的。有一类新的光感受器，固有的光敏视网膜神经节细胞(IpRGC)，在这个阶段是完全功能的。对于ipRGC、光暴露和视网膜波之间可能的相互作用，我们几乎一无所知。这项提议不仅探讨了这些光感受器如何受到视网膜波的影响，而且还探讨了它们如何反过来影响波。在成人视网膜，ipRGC不仅接受兴奋性和抑制性突触输入，而且被认为将信号反馈到视网膜内部。这增加了视网膜波和ipRGC之间双向相互作用的可能性，尽管ipRGC在这个发育阶段的视网膜内突触连接尚未确定。初步数据表明，ipRGCs放电不仅与视网膜波有关，而且这类神经节细胞的光激活也改变了视网膜波的活动。因此，本提案的具体目的是：1.表征视网膜波活动中ipRGCs的兴奋，并确定其激活机制；2.检验光诱导的ipRGCs激活改变视网膜波活动的假说，并评估相关机制。这些研究将为视网膜波活动的机制提供新的线索，并将扩展我们对ipRGCs的理解，ipRGCs在昼夜节律光携带和瞳孔光反射中发挥着指导作用。 公共卫生相关性： 这项研究将考察一类特殊的视网膜细胞在调节正常视觉系统发育中的作用。此外，它将为这些细胞在发育早期如何发挥作用提供新的线索。这些细胞在成人身体对日光的反应中发挥着核心作用，因此，这些研究与公共健康问题有关，如时差、季节性情感障碍、盲人昼夜节律紊乱，以及倒班工作的负面后果，包括表现受损、受伤风险增加，甚至癌症发病率上升。

DESCRIPTION (provided by applicant): Retinal waves comprise zones of spontaneous activation that propagate across the immature retina. These waves are thought to participate in the development of retinotopic maps and the segregation of binocular inputs to the superior colliculus and lateral geniculate nucleus. Retinal waves occur before rod and cone photoreceptors are mature, at a time when the retina has been considered insensitive to light. However, recent findings invalidate this assumption. There is a novel class of photoreceptor, the intrinsically photosensitive retinal ganglion cell (ipRGC), that is fully functional at this stage. Virtually nothing is known about possible interactions between ipRGCs, light exposure, and retinal waves. This proposal explores not only how these photoreceptors are affected by retinal waves, but also how they, in turn, may affect the waves. In the adult retina, ipRGCs not only receive excitatory and inhibitory synaptic input, but also are thought to feed signals back into the inner retina. This raises the possibility of bidirectional interactions between retinal waves and ipRGCs, although the intraretinal synaptic connectivity of ipRGCs at this developmental stage has not been determined. Preliminary data indicate that not only do ipRGCs discharge in association with retinal waves, but also that photic activation of this class of ganglion cells alters retinal wave activity. Therefore, the specific aims of this proposal are: 1. Characterize excitation of ipRGCs during retinal wave activity and identify the mechanism of activation; 2. Test the hypothesis that light-induced activation of ipRGCs alters retinal wave activity and assess the mechanism responsible. These studies will shed new light on the mechanism of retinal wave activity and will extend our understanding of ipRGCs, which play an instructive role in circadian rhythm photoentrainment and the pupillary light reflex. PUBLIC HEALTH RELEVANCE: This study will examine the role of a specialized class of retinal cells in the regulation of normal visual system development. Further, it will shed new light on how these cells function early in development. These cells play a central role in the adult body's response to daylight and therefore, these studies are relevant to such public health issues as jet lag, seasonal affective disorder, circadian disruption in the blind, and the negative consequences of shift work including impaired performance, increased risk of injury and even elevated cancer rates.