Physiology of the Vertebrate Retina

描述（由申请人提供）：激发的自发波， 发生在发育中的视网膜在一个特定的时间段， 视觉的开始，被认为是发展的重要线索， 视觉系统中精确的神经元连接。然而，机制 这些视网膜波的形成和调节的基础是未知的。 这项竞争性续签申请中提出的研究将进行调查 神经元的相互作用对生成、繁殖和调节很重要 自发波在发展中的视网膜，重点是 星突无长突和神经节中神经递质介导的相互作用 细胞通过一系列精心挑选的具体目标，这些研究将 测试一般假设的几个关键和具体方面， 哺乳动物视网膜中的自发波在很大程度上是由 多种神经递质系统相互作用， 依赖年龄的方式。这些具体目标旨在：（1）确定 发育中的胆碱能、谷氨酸能、甘氨酸能和GABA能 系统的形成自发神经元活动的各个阶段， 视网膜发育;（2）了解的节奏和时间调节 自发视网膜波;（3）确定波之间的相互关系 动力学、神经元活动和递质相互作用。 为了实现上述目标，细胞生理和药理学 实验的目的是利用独特的整体安装， 视网膜准备，它允许整合一些尖端的 神经生理学技术，包括同步Ca 2+成像， 膜片钳记录，来自识别的细胞对的双膜片钳记录， 和活体视网膜神经元的粒子传递荧光标记。这 全面的方法将使调查人员能够在 突触，细胞和网络水平，视网膜波的关键数据 这是以前在其他实验环境中无法实现的。从这些 研究有望提供关于神经元的急需的信息， 相互作用和自发兴奋在发展中的视网膜，从而允许 更好地了解健康人的视觉发育和视网膜处理 和病态的国家

DESCRIPTION (provided by applicant): Spontaneous waves of excitation, which occur in the developing retina during a specific time period immediately before the onset of vision, are believed to provide important cues for the development of precise neuronal connectivity in the visual system. However, the mechanisms underlying the formation and regulation of these retinal waves are unknown. Studies proposed in this competing renewal application will investigate neuronal interactions important for the generation, propagation, and regulation of spontaneous waves in the developing retina, with an emphasis on neurotransmitter-mediated interactions in starburst amacrine and ganglion cells. Through a set of carefully selected specific aims, these studies will test several critical and specific aspects of the general hypothesis that spontaneous waves in the mammalian retina are mediated, to a large extent, by multiple neurotransmitter systems interacting in a highly coordinated and age-dependent manner. These specific aims aim to: (1) identify the contribution of the developing cholinergic, glutamatergic, glycinergic, and GABAergic systems to the formation of spontaneous neuronal activity at various stages of retinal development; (2) understand the rhythmicity and temporal regulation of spontaneous retinal waves; and (3) identify the interrelationship among wave dynamics, neuronal activity, and transmitter interaction. To achieve the above aims, cellular physiological and pharmacological experiments have been designed to take advantage of a unique whole-mount retinal preparation, which allows the integration of a number of cutting-edge neurophysiological techniques, including simultaneous Ca2+ imaging and patch-clamp recording, dual patch-clamp recording from identified cell pairs, and particle-delivered fluorescent labeling of living retinal neurons. This comprehensive approach will enable the investigators to obtain, at the synaptic, cellular, and network levels, critical data on retinal waves previously unattainable in other experimental settings. Results from these studies are expected to provide much needed information about neuronal interaction and spontaneous excitation in the developing retina, thus allowing better understanding of visual development and retinal processing in healthy and diseased states.