The Assembly of Synaptic Circuits in the Mammalian Retina

在出生之前，在与外界交流之前，神经系统会自发地产生高度模式化的活动。费勒博士在发育中的视网膜中研究这一现象。在视觉成为可能之前，邻近的视网膜神经节细胞，也就是投射到大脑的视网膜神经元，自发地发射相关的动作电位脉冲，以波的形式传播到整个视网膜。这种相互关联的活动被称为视网膜波，这是适当细化视网膜投射到大脑中的目标所必需的。在睁开眼睛之前，有一个视网膜发育阶段，在此期间，视网膜回路逐渐从产生视网膜波过渡到介导光诱发反应，这是视觉处理的第一阶段。在这个过渡期间，这两个功能电路共存了几天。关于视网膜本身可能高度可塑性的这一关键发展阶段，有两个问题被解决。首先，视网膜波是如何产生的？将在急性分离的小鼠视网膜上进行复杂的生理学和成像实验，以识别视网膜波背后的电路。其次，视网膜波和光诱发反应如何相互作用来决定视网膜的放电模式？一个专门的电极阵列将被用来同时记录数十个视网膜神经节细胞的数据，以确定介导波和光诱发活动的电路之间的相互作用。这些实验将有助于更好地理解自发活动与感觉驱动活动在神经回路组装中的作用。此外，该项目的资金将支持对两名新接触神经生物学的年轻科学家的培训。第一位是博士后研究员阿纳斯塔西娅·阿尼先科，她获得了理论物理学博士学位。第二位是研究生亚伦·汉比，他是一名分子生物学家。此外，这项研究的结果将被用作一门发展神经生物学本科课程的材料，该课程强调神经回路的构建。

Prior to birth, before there is communication with the outside world, the nervous system is spontaneously generating highly patterned activity. Dr. Feller studies this phenomenon in the developing retina. Before vision is possible, neighboring retinal ganglion cells, the neurons of the retina that project to the brain, spontaneously fire correlated bursts of action potentials that propagate across the retina in the form of waves. This correlated activity, termed retinal waves, is required for the proper refinement of retinal projections to targets in the brain. There is a stage of retinal development immediately preceding eye-opening during which retinal circuits gradually transition from generating retinal waves to mediating light-evoked responses that are the first stage of visual processing. During this transition, these two functional circuits coexist for several days. Two questions regarding this critical stage of development, when the retina itself may be highly plastic are addressed. First, how are retinal waves generated? Sophisticated physiology and imaging experiments will be conducted on acutely isolated mouse retina are used to identify the circuit that underlies retinal waves. Second, how do retinal waves and light-evoked responses interact to determine the firing pattern in the retina? A specialized array of electrodes will be used to record simultaneously from dozens of retinal ganglion cells to determine the interaction between the circuits that mediate waves and light-evoked activity. These experiments will help to better understand the role of spontaneous vs. sensory driven activity in the assembly of neural circuits. In addition, the funds from this project will support the training of two young scientists who are new to Neurobiology. The first is a postdoctoral researcher, Anastasia Anishchenko, who received her Ph. D. in theoretical physics. The second is graduate student, Aaron Hamby, who is trained as a molecular biologist. In addition, the results of this research will be used as material for an undergraduate course on developmental neurobiology that emphasizes the construction of neural circuits.