Development of Synaptic Pathways in Retina

描述（由申请人提供）：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经验修改的。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导到大脑。这些平行通道的一个基本特征是将光诱发信号分离为ON和OFF通路。在视网膜、外侧膝状核（LGN）和视觉皮层中，这两条平行通路在很大程度上是分开的。在生命早期，视觉诱发活动影响LGN和视觉皮层中这些通路的连通性和活性。我们最近的研究表明，这些通路的连通性和活动也受到视网膜视觉经验的调节。

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.