Development of Synaptic Pathways in Retina

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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.