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

描述（由申请人提供）：模式化自发活动的显示是未成熟神经系统的一种新兴特性，被认为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）制备物在相邻的视网膜神经节细胞（RGC）之间表现出传播电活动，称为“视网膜波”。由于RGC将视觉信息传递到中枢神经系统中的高级结构，因此视网膜波被认为在上级丘（SC）、外侧膝状体核（LGN）和视觉皮层（VCtx）中的地形神经图的活动依赖性细化中起关键作用。然而，视网膜波在神经回路发育中的作用仍然存在很大的争议，部分原因是它们的存在从未在体内得到证实。以前的工作使用细胞外微电极记录技术在体内表现出有限的和局部相关的尖峰对胚胎大鼠RGC之间，但没有评估波活动已在体内进行，可能是因为与记录从一个大的队列的RGC在新生动物的方法学挑战。在这个提议中，我们使用一种非常新颖的成像方法来检查和表征整个视觉神经轴的自发活动，包括RGCs，SC和VCtx，在新生小鼠体内。我们试图建立自发活动的行波是否发生在清醒的，行为的新生小鼠，并检查出生后的前两周内整个发育中的视觉系统的波的时空特性。我们的初步数据表明，自发性视网膜波存在至少一个星期的发展在体内，并表现出类似的配置文件的时空特性，如先前所述的体外。此外，视网膜波在中脑和视觉皮层中产生匹配的活动模式。鉴于视网膜波在小鼠睁眼前的时期内的显着保真度，我们在这里报告在体内，连同先前的工作表明猕猴视网膜内的自发波在出生前就存在于体外，在人类胎儿发育期间，视觉系统在相当长的妊娠期内经历视网膜波的模式激活，这可能对形成功能成熟至关重要。在感官体验开始之前的神经回路。总之，这些实验的目的是研究在哺乳动物视觉系统的神经回路的发展中，在体内的模式化自发活动的性质和作用。

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.