Physiology of the Vertebrate Retina

描述(申请人提供)：自发激发波， 发生在发育中的视网膜中，在此之前的特定时间段 视觉的开始，被认为为发育提供了重要的线索 视觉系统中精确的神经元连接。然而，这些机制 这些视网膜波的形成和调节机制尚不清楚。 在这项竞争性续签申请中提出的研究将调查 神经元之间的相互作用对神经元的产生、繁殖和调节很重要 在发育中的视网膜中的自发波，重点是 星状爆发无长突细胞和神经节中神经递质的相互作用 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 多个神经递质系统在高度协调和 依赖年龄的方式。这些具体目标旨在：(1)确定贡献 发育中的胆碱能、谷氨酸能、甘氨酸能和GABA能 在不同阶段自发神经元活动形成的系统 视网膜发育；(2)了解视网膜的节律性和时间调节。 自发性视网膜波；以及(3)识别波之间的相互关系 动力学、神经元活动和递质相互作用。 为了达到上述目的，细胞生理学和药理学 实验被设计成利用一种独特的整体安装 视网膜准备，这让整合了多项前沿技术 神经生理学技术，包括同时进行钙离子成像和 膜片钳记录，来自识别的细胞对的双膜片钳记录， 以及活的视网膜神经元的颗粒递送荧光标记。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 以前在其他实验环境中无法达到。来自这些的结果 预计研究将提供关于神经元的迫切需要的信息 在发育中的视网膜中的相互作用和自发兴奋，从而允许 更好地了解健康人的视觉发育和视网膜处理 以及疾病缠身的州。

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.