In Vivo Properties of Spontaneous Waves in the Retina and Developing Visual Syste

视网膜自发波的体内特性和发育中的视觉系统

基本信息

批准号：
9011532
负责人：
Michael C. Crair
金额：
$ 41.63万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-02-01 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9011532
关键词：
Age related macular degeneration Amblyopia Axon Behavior Biological Assay Biological Models Birth Brain Complex Data Development Disease Embryo Exhibits Eye Fetal Development Genetic Models Genetic Techniques Glaucoma Health Higher Order Chromatin Structure Human Image In Vitro Knock-out Knockout Mice Lateral Geniculate Body Macaca Mammals Maps Mediating Microelectrodes Midbrain structure Modeling Molecular Molecular Genetics Motor Cortex Mus Nature Neonatal Nervous system structure Neuraxis Neurons Newborn Animals Pattern Play Preparation Property Rattus Reporter Reporting Resolution Retina Retinal Retinal Ganglion Cells Role Sensory Shapes Somatosensory Cortex Staging Strabismus Synapses Techniques Testing Transgenic Organisms Trauma Travel Vision Visual Visual Cortex Visual system structure Work awake base cohort cortex mapping design experience extracellular extrastriate visual cortex in vivo interest mutant neural circuit novel preference relating to nervous system research study response retinotopic self organization spatiotemporal superior colliculus Corpora quadrigemina two-photon visual information visual map

项目摘要

DESCRIPTION (provided by applicant): The display of patterned spontaneous activity is an emergent property of the immature nervous system that is thought to mediate synaptic competition and instruct self- organization in many developing neural circuits. In the visual system, isolated (in vitro) preparations of developing retina exhibit propagating electrical activiy amongst neighboring retinal ganglion cells (RGCs), termed 'retinal waves'. Since RGCs relay visual information to higher order structures in the central nervous system, retinal waves are thought to play a key role in activity-dependent refinement of topographic neural maps in the superior colliculus (SC), lateral geniculate nucleus (LGN), and visual cortex (VCtx). However, the role of retinal waves in neural circuit development remains remarkably controversial, in part because their existence has never been demonstrated in vivo. Previous work using extracellular microelectrode recording techniques in vivo demonstrated limited and local correlated spiking between pairs of embryonic rat RGCs, but no assessment of wave activity has been undertaken in vivo, likely because of the methodological challenges associated with recording from a large cohort of RGCs in neonatal animals. In this proposal, we use a highly novel imaging approach to examine and characterize spontaneous activity throughout the visual neuraxis, including RGCs, the SC and VCtx, in neonatal mice in vivo. We seek to establish whether traveling waves of spontaneous activity occur in awake, behaving neonatal mice, and examine the spatiotemporal properties of waves throughout the developing visual system during the first two weeks after birth. Our preliminary data indicates that spontaneous retinal waves are present for at least a week of development in vivo and exhibit a similar profile of spatiotemporal properties as those described previously in vitro. Moreover, retinal waves generate matched activity patterns in the midbrain and visual cortex. Given the remarkable fidelity of retinal waves during the period prior to eye opening in mice we report here in vivo, together with previous work demonstrating that spontaneous waves within macaque retina are present in vitro before birth, it seems likely that the visual system experiences patterned activation by retinal waves for a substantial gestational period during human fetal development that may be crucial for shaping the functional maturation of neural circuits before the onset of sensory experience. In all, these experiments are designed to investigate the properties and role of patterned spontaneous activity in vivo in the development of neural circuits in the mammalian visual system.

描述（由申请人提供）：展示图案的自发活动是未成熟神经系统的新兴属性，被认为可以介导突触竞争并指导许多正在发展的神经回路中的自我组织。在视觉系统中，在邻近的视网膜神经节细胞（RGC）之间表现出视网膜发育的分离（体外）制剂，称为“视网膜波”。由于中枢神经系统中的RGC传递了视觉信息到高阶结构，因此认为视网膜波在上丘丘（SC）（SC），外侧遗传核（LGN）和Visual Cortex（VCTX）中的地形神经图（SC）中的地形神经图中起关键作用。然而，视网膜波在神经回路发育中的作用仍然引起极大的争议，部分原因是它们的存在在体内从未被证明。先前在体内使用细胞外微电极记录技术的工作表明，在成对的胚胎大鼠RGC对之间的局部相关峰值有限，但在体内没有对波活性进行评估，这很可能是因为与新生儿动物中RGC的大量RGC相关的方法学挑战。在此提案中，我们使用一种高度新颖的成像方法来检查和表征整个视觉神经性的自发活动，包括RGC，SC和VCTX在NeonaTal小鼠的体内。我们寻求确定自发活动的行进波是否发生在清醒中，表现为新生儿小鼠，并在出生后的前两周内检查整个发育中的视觉系统的波浪的时空特性。我们的初步数据表明，在体内至少有一个星期的发育中存在自发的视网膜波，并且具有与先前在体外描述的时空特性相似的时空特性。此外，视网膜波在中脑和视觉皮层中产生匹配的活动模式。鉴于在小鼠睁眼之前的一段时间内，您在体内报告了视网膜波的明显保真度经验。总的来说，这些实验旨在研究体内图案化自发活动在哺乳动物视觉系统中神经回路发展中的特性和作用。