The Function of Neural Activity in Developing Retina

项目总结/摘要 自发活动是神经系统发育的标志。未成熟的在视觉成熟之前，未成熟的 视网膜神经元自发地产生相关活动。这种活动以行动波的形式传播 扫描整个视网膜神经节细胞层的电位。视网膜波从胚胎第16天持续到 出生后两周，视网膜内的功能回路出现和视网膜发育的发育期。 对大脑的投射正在经历大量的改进。在这里，我们探讨三个目标， 视网膜波功能的潜在机制。 在目标1中，我们专注于了解介导胚胎视网膜波的电路。在这个年龄，视网膜 由视网膜神经节细胞、少数无长突细胞和广泛的成神经细胞层组成， 细胞类型正在分化。尽管缺乏成熟的电路元件，视网膜波是强大的。在这里我们测试 关于间隙连接耦联和突触传递在介导这些过程中的相对作用的假说， 波 在目标2中，我们专注于出生后第二周，此时视网膜波表现出深刻的传播偏差。在此 在一段时间内，大多数波在鼻方向上行进，这是一种模仿诱导的光流的发射模式。 通过向前运动。在这里，我们探讨的假设，这种不对称的传播活动是由于 GABA能中间神经元之间的不对称连接， 电路. 最后，在目标3中，我们研究了视网膜波和视觉刺激对光敏感的视网膜神经节的作用 在发育中的视网膜中释放多巴胺的细胞。虽然多巴胺在几个方面起着关键作用， 发展过程中，什么控制释放是未知的。我们将采用一种新的成像方法， 用于测量与钙瞬变并行的阶段性多巴胺释放。使用这种方法，我们将探索 视网膜波和光刺激在发育过程中介导多巴胺释放的相对作用。

PROJECT SUMMARY/ABSTRACT Spontaneous activity is a hallmark of developing neural systems. Prior to the maturation of vision, immature retinal neurons spontaneously generate correlated activity. This activity propagates in the form of waves of action potentials that sweep across the retinal ganglion cell layer. Retinal waves persist from embryonic day 16 through two weeks after birth, a developmental period when functional circuits within the retina are emerging and retinal projections to the brain are undergoing a tremendous amount of refinement. Here we explore three Aims regarding mechanisms underlying the function of retinal waves. In Aim 1, we focus on understanding the circuits that mediate embryonic retinal waves. At this age, the retina is comprised of retinal ganglion cells, a few amacrine cells, and an extensive neuroblastic layer in which the other cell types are differentiating. Despite the lack of mature circuit elements, retinal waves are robust. Here we test hypotheses regarding the relative role of gap junction coupling and synaptic transmission in mediating these waves. In Aim 2 we focus on second postnatal week when retinal waves exhibit a profound propagation bias. During this time period, the majority of waves travel in the nasal direction, a firing pattern which mimics optic flow induced by forward motion. Here we explore the hypothesis that this asymmetry in propagating activity is due to asymmetric connectivity between a GABAergic interneurons that are well integrated into wave generating circuits. Finally, in Aim 3 we investigate the role of retinal waves and visual stimulation of light-sensitive retinal ganglion cells in the release of dopamine in the developing retina. Though dopamine plays a key role in several developmental processes, what controls release is unknown. We will employ a novel imaging method that allows for measuring phasic dopamine release in parallel with calcium transients. Using this method, we will explore the relative role of retinal waves and light stimulation in mediating dopamine release during development.”