Function of neural activity in developing retina

未成熟的视网膜神经元自发地以波的形式产生相关的活动 横扫视网膜神经节细胞层的动作电位。这些视网膜波会出现 在发育期间，视网膜内的功能回路正在出现， 视网膜对大脑的投射正在经历着巨大的精细化。尽管 在阐明调节这些波的电路方面已经取得了重大进展， 可靠地产生视网膜波的机制尚不完全清楚。 在这里，我们将探索产生视网膜波的电路。视网膜波是 在不同的发育阶段由不同的回路调节。在出生后的第一周， 一种由胆碱能中间神经元组成的回路，称为星状爆发无长突细胞(SACs)， 调和波。在出生后第二周，谷氨酸能中间神经元被称为 双极细胞负责调节电波。虽然胆碱能和谷氨酸能波是由 不同的电路，它们有一个共同的特征：去极化在 没有直接的突触连接。利用双光子钙成像技术及其最新进展 测量[？]的光学传感器突触外释放ACh和谷氨酸，我们将测试 假设这些波通过体积传输传播。此外，我们还将研究 视网膜固有感光性神经节细胞对视网膜波的影响。 虽然ipRGC确实调制了WT小鼠的波，但它们更戏剧性地调制了 在缺乏烟碱？2亚单位的基因敲除小鼠中发现的代偿波 乙酰胆碱受体(？2KO)。2KO小鼠表现出显著不同的模式 自发活动超过WT小鼠，因此已被作为主要的模型系统 以了解视网膜波在视觉系统发育中的作用。我们建议使用 WT和？2KO小鼠在ipRGCs中表达GFP的多电极和靶向记录 探索ipRGC调节发育中视网膜放电模式的新假说 通过改变多巴胺水平。 这项工作将涉及负责以下工作的一般组织原则 产生驱动依赖于活动的发育过程的活动模式。它 也应该阐明支配人类正常发展的原则 神经系统，从而使了解神经系统出生缺陷的起源成为可能 并设计使神经系统能够再生起作用的神经的策略 受伤后的巡回赛。

Immature retinal neurons spontaneously generate correlated activity in the form of waves of action potentials that sweep across the retinal ganglion cell layer. These retinal waves occur during the developmental period when functional circuits within the retina are emerging and retinal projections to the brain are undergoing a tremendous amount of refinement. Though significant progress in elucidating the circuits that mediate these waves has been achieved, the mechanisms that underlie the reliable generation of retinal waves is not fully understood. Here we explore the circuits that robustly generate retinal waves. Retinal waves are mediated by different circuits at different stages of development. In the first postnatal week, a circuit consisting of cholinergic interneurons, called starburst amacrine cells (SACs), mediates waves. During the second postnatal week, glutamatergic interneurons called bipolar cells mediate waves. Although cholinergic and glutamatergic waves are mediated by distinct circuits, they share one characteristic: the depolarization propagates across cells that do not have direct synaptic connections. Using two-photon calcium imaging and state-of-art optical sensors that measure[?] extrasynaptic release of ACh and glutamate, we will test the hypothesis that these waves propagate via volume transmission. In addition, we will study the influence of intrinsically photosensitive retinal ganglion cells (ipRGCs) on retinal waves. While ipRGCs do modulate waves in WT mice, they more dramatically modulate the compensatory waves found in knockout mice lacking the ¿2 subunit of the nicotinic acetylcholine receptor (¿2KO). ¿2KO mice exhibit significantly different patterns of spontaneous activity than WT mice, and therefore have served as a primary model system for understanding the role of retinal waves in visual system development. We propose using multielectrode and targeted recordings from WT and ¿2KO mice expressing GFP in ipRGCs to explore the novel hypothesis that ipRGCs regulate firing patterns in the developing retina by altering the dopamine level. This work will address the principles of general organization that are responsible for generating the activity patterns that drive activity-dependent developmental processes. It should also elucidate the principles that govern the normal development of the human nervous system, thus making it possible to understand the origin of neurological birth defects and to devise strategies that enable the nervous system to regenerate functioning neural circuits after injury.