Development of Synaptic Pathways in Retina

描述(申请人提供)：我研究的长期目标是了解视网膜回路是如何形成的，以及它们是如何被视觉体验改变的。视觉场景的神经元图像由视网膜处理，并通过一组分离的时空通道传递到大脑。这些平行通道的一个基本特征是将光诱发信号分离成接通和断开通路。在视网膜、外侧膝状体(LGN)和视皮层中，这两条平行的通路在很大程度上保持分离。在生命早期，视觉诱发活动影响这些通路在LGN和视皮层的连通性和活性。我们最近的研究表明，这些通路的连通性和活性也受到视网膜视觉经验的调节。 本研究的第一个目的是确定是否存在视觉经验对睁眼后视网膜开关通路的细化起关键作用的时间段，以及光剥夺对开关通路细化的影响是否可逆。为此，将使用电生理学和解剖学方法研究RGC的光反应及其树突分支的模式。在周期性光/暗条件和恒定黑暗条件下饲养的小鼠，将确定光剥夺对开关通路精细化的影响的发育概况、临界期和可逆性。 第二个目标是确定突触机制，通过这种机制，开关通路的发育完善受到视觉经验的调节。来自ON和OFF双极细胞的自发和光诱发突触输入在ON-OFF通路的发育完善中的作用将通过转基因小鼠来检验，在转基因小鼠中，来自ON或OFF通路的自发和光诱发突触输入被改变。此外，睁开眼睛后是否通过树突修剪来细化视网膜节细胞的开和离通路，将使用延时、共聚焦成像技术来确定。这些研究的结果对我们如何看待影响婴儿期和儿童期视力的病理具有重要意义。他们还提供了关于视网膜中活性依赖的突触细化如何影响我们对视觉皮质中活性依赖的突触可塑性的解释的见解。

DESCRIPTION (provided by applicant): The long-term objectives of my research are to understand how retinal circuits are formed and how they are modified by visual experience. The neuronal image of the visual scene is processed by the retina and conducted to the brain by a set of separated spatio-temporal channels. A fundamental feature of these parallel channels is the separation of light evoked signals into ON and OFF pathways. These two parallel pathways remain separated to a large extent in the retina, the lateral geniculate nucleus (LGN) and the visual cortex. In early life, visual-evoked activity affects the connectivity and activity of these pathways in LGN and visual cortex. Our recent study showed that the connectivity and activity of these pathways are also regulated by visual experience in retina. The first goal of this study is to determine whether there is a time period during which visual experience is critical for the refinement of ON-OFF pathways in retina after eye opening and whether the effect induced by light deprivation on the ON-OFF pathway refinement is reversible. Toward this end RGC light responses and the patterns of their dendritic ramification will be examined using electrophysiological and anatomical approaches. The developmental profile, critical period and reversibility of the effects induced by light deprivation on the refinement of ON-OFF pathways will be determined in mice raised under cyclic light/dark conditions and in constant darkness. The second goal is to identify the synaptic mechanisms, by which the developmental refinement of ON-OFF pathways is regulated by visual experience. The roles of spontaneous and light evoked synaptic inputs from ON and OFF bipolar cells on the developmental refinement of ON-OFF pathways will be examined using transgenic mice in which the spontaneous and light evoked synaptic inputs from ON or OFF pathways are altered. In addition, whether the ON and OFF pathways are refined in RGCs through dendritic pruning after eye opening will be determined using time-lapse, confocal imaging techniques. The results of these studies have important implications in how we view pathologies that affect vision during infancy and childhood. They also provide insights to how activity dependent synaptic refinement in retina could affect our interpretation of activity-dependent synaptic plasticity in visual cortex.