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

描述(申请人提供)：显示有模式的自发活动是未成熟神经系统的一种新特性，被认为在许多发育中的神经回路中调节突触竞争并指导自组织。在视觉系统中，发育中的视网膜的分离(体外)准备显示出在邻近的视网膜神经节细胞(RGC)之间传播电活动，被称为“视网膜波”。由于RGCs将视觉信息传递给中枢神经系统的高级结构，视网膜波被认为在上丘(SC)、外侧膝状体(LGN)和视皮层(VCtx)的活动依赖神经地形图的精细化中发挥关键作用。然而，视网膜波在神经回路发育中的作用仍然存在显著的争议，部分原因是它们的存在从未在体内得到证明。先前在活体中使用细胞外微电极记录技术的工作显示了胚胎大鼠视网膜神经节细胞对之间有限的和局部相关的尖峰，但还没有在体内进行波活动的评估，可能是因为从新生动物的大量视网膜节细胞记录相关的方法学挑战。在这项建议中，我们使用一种非常新颖的成像方法来检查和表征整个视神经轴的自发活动，包括视网膜神经节细胞、SC和VCtx，在体内。我们试图确定在清醒的、行为正常的新生小鼠中是否存在自发活动的行波，并检查出生后头两周整个发育中的视觉系统中的行波的时空特性。我们的初步数据表明，自发性视网膜波在体内发育至少一周，并显示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质产生匹配的活动模式。鉴于我们在活体中报告的小鼠睁眼前一段时间视网膜波的惊人保真度，加上之前的工作表明，猕猴视网膜内的自发波在出生前就存在于体外，似乎很可能在人类胚胎发育期间的相当长的妊娠期内，视觉系统经历了视网膜波的模式激活，这可能对于在感觉体验开始之前塑造神经回路的功能成熟至关重要。总而言之，这些实验旨在研究在哺乳动物视觉系统的神经回路发育中，活体内有模式的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.