ipRGC participation and modulation of retinal wave activity

ipRGC 参与和调节视网膜波活动

• 批准号: 8216456
• 负责人: Jordan Michael Renna
• 金额: $ 5.3万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-03 至 2013-08-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8216456
• 关键词: Adult; Affect; Back; Cell physiology; Cells; Circadian Rhythms; Data; Development; Injury; Jet Lag Syndrome; Lateral Geniculate Body; Light; Malignant Neoplasms; Maps; Mediating; Nicotinic Receptors; Performance; Photoreceptors; Play; Population; Public Health; Pupil light reflex; Regulation; Retina; Retinal; Retinal Cone; Retinal Ganglion Cells; Risk; Role; Seasonal Affective Disorder; Signal Transduction; Staging; Synapses; Testing; Time; blind; electrical property; feeding; ganglion cell; melanopsin; novel; photoactivation; presynaptic; public health relevance; response; retinal rods; retinotopic; segregation; shift work; superior colliculus Corpora quadrigemina; vision development

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.

描述（由申请人提供）： 视网膜波包括自发激活的区域，这些区域在未成熟的视网膜上传播。这些波被认为参与了视网膜图的发展以及双眼输入到上丘和侧元核的隔离。在视网膜被认为对光不敏感的时候，视网膜波在杆和锥形感光体成熟之前发生。但是，最近的发现使这一假设无效。在现阶段，有一类新型的光感受器，即本质上光敏的视网膜神经节细胞（IPRGC）。实际上，关于IPRGC，光曝光和视网膜波之间可能的相互作用，几乎一无所知。该建议不仅探讨了这些感光体如何受到视网膜波的影响，而且还探讨了它们如何影响波。在成年视网膜中，IPRGC不仅接收兴奋性和抑制性突触输入，而且被认为可以将信号送回内部视网膜。尽管尚未确定IPRGC的视网膜内突触连通性，但尚未确定视网膜波和IPRGC之间双向相互作用的可能性。初步数据表明，IPRGC不仅与视网膜波相关，而且该类别的神经节细胞的光激活会改变视网膜波活性。因此，该提案的具体目的是：1。表征视网膜波活性期间IPRGC的激发并确定激活的机理； 2。检验以下假设：光诱导的IPRGC激活改变了视网膜波活性并评估负责的机制。这些研究将为视网膜波活性的机理提供新的启示，并将扩展我们对IPRGC的理解，IPRGC在昼夜节律光膜片和瞳孔光反射中起着启发性作用。 公共卫生相关性： 这项研究将研究专门的视网膜细胞在调节正常视觉系统发展中的作用。此外，它将为这些细胞在发育早期的发挥作用提供新的启示。这些细胞在成年人身体对日光的反应中起着核心作用，因此，这些研究与诸如喷气滞后，季节性情感障碍，盲目的昼夜节律破坏以及班次工作的负面后果（包括绩效受损，受伤的风险增加，甚至升高癌症率）涉及公共卫生问题。