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

• 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
• 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

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）：模式化自发活动的展示是不成熟神经系统的一种新兴特性，被认为可以介导突触竞争并指导许多发育中的神经回路的自组织。在视觉系统中，发育中的视网膜的分离（体外）制剂表现出在邻近视网膜神经节细胞（RGC）之间传播电活动，称为“视网膜波”。由于 RGC 将视觉信息传递给中枢神经系统的高级结构，因此视网膜波被认为在上丘 (SC)、外侧膝状核 (LGN) 和视觉神经拓扑图的活动依赖性细化中发挥着关键作用。皮质（VCtx）。然而，视网膜波在神经回路发育中的作用仍然存在很大争议，部分原因是它们的存在从未在体内得到证实。先前在体内使用细胞外微电极记录技术的工作证明了成对胚胎大鼠 RGC 之间的有限且局部相关的尖峰，但尚未对体内波活动进行评估，这可能是因为与从大量 RGC 中进行记录相关的方法学挑战。新生动物。在本提案中，我们使用一种高度新颖的成像方法来检查和表征新生小鼠体内整个视觉神经轴的自发活动，包括 RGC、SC 和 VCtx。我们试图确定自发活动的行波是否发生在清醒、行为正常的新生小鼠中，并检查出生后前两周整个发育中的视觉系统中波的时空特性。我们的初步数据表明，自发视网膜波在体内发育至少一周，并且表现出与先前在体外描述的相似的时空特性。此外，视网膜波在中脑和视觉皮层中产生匹配的活动模式。鉴于我们在体内报道的小鼠在睁眼之前的时期视网膜电波的显着保真度，以及之前的工作证明猕猴视网膜内的自发电波在出生前就存在于体外，视觉系统似乎经历了模式化激活在人类胎儿发育过程中的相当长的妊娠期内，视网膜电波的影响可能对于在感觉体验开始之前形成神经回路的功能成熟至关重要。总之，这些实验旨在研究体内模式化自发活动在哺乳动物视觉系统神经回路发育中的特性和作用。