Function of Neural Activity in Developing Retina

描述（申请人提供）：将研究发育中的哺乳动物视网膜中自发神经活动的机制和功能。未成熟的视网膜神经元自发地以动作电位波的形式产生相关活动，席卷视网膜神经节细胞层。这些“视网膜波”发生在视网膜神经节细胞轴突在外侧膝状核中分离成眼特异性层的发育期间。利用光学成像、单细胞电生理学和多电极阵列记录相结合的实验来研究视网膜波产生的细胞间耦合机制。首先，利用基因敲除小鼠，我们将确定一个特定的间隙连接耦合网络在视网膜神经节细胞自发动作电位相关结构产生中的作用。其次，我们将研究神经调节剂腺苷和GABA有效调节网络活动的机制。这项工作的一个结果将是确定负责生成驱动依赖于活动的开发过程所需的活动模式的一般组织原则。这项工作将进一步加深我们对控制人类神经系统正常发育的组织原则的理解，使我们有可能了解神经出生缺陷的起源，并设计出允许神经系统在损伤后再生功能神经回路的策略。

DESCRIPTION (provided by applicant): The mechanisms and function of spontaneous neural activity in the developing mammalian retina will be studied. 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 retinal ganglion cell axons are segregating into eye-specific layers in the lateral geniculate nucleus. Experiments using a combination optical imaging, single cell electrophysiology, and multielectrode array recordings are proposed to investigate the mechanisms of inter-cellular coupling that underlie the generation of retinal waves. First, using knockout mice, we will identify the role of a particular gap junction coupled network in generating the correlation structure of spontaneous action potentials in retinal ganglion cells. Second, we will study the mechanisms underlying the ability of the neuromodulators adenosine and GABA to powerfully modulate network activity. One result of this work will be to determine general organizations principles responsible for generating the activity patterns required for driving activity-dependent developmental processes. This work should further our understanding of the organizing principles that govern the normal development of the human nervous system, making it possible to understand the origin of neurological birth defects and to devise strategies that allow the nervous system to regenerate functioning neural circuits after injury.