Synaptic connections within the vertebrate retina are highly organized both structurally and functionally. Our broad goal is to elucidate the mechanisms underlying the precision by which retinal circuits are assembled during development. Retinal ganglion cells (RGCs) that relay information from the eye to visual targets in the brain receive connections from two major classes of retinal interneurons, the amacrine cells and bipolar cells. Together, these retinal interneurons help shape the response properties of RGCs to light stimuli. Bipolar cells, which use glutamate as a neurotransmitter, form the essential link between photoreceptors and RGCs. Synaptic connections between bipolar cells and RGCs are precisely organized at maturity. The specific goal in this proposal is to determine how bipolar cells connect with RGCs during development, and ascertain how activity in the retina before vision helps shape the connectivity between these cell types.
In Aim 1, the distribution and densities of bipolar inputs onto RGCs will be mapped across development, by expressing in RGCs fluorescently-tagged PSD95 (PSD95-FP), a postsynaptic protein localized to glutamatergic synapses. Live imaging approaches will be used to test the hypothesis that bipolar connectivity patterns are established by a process of synapse formation and elimination, and that their connectivity patterns are organized in part by structural remodeling of the RGC dendritic arbor.
In Aim 2, the importance of light-independent photoreceptor transmission in the maturation of bipolar-RGC connectivity will be determined by examining how RGC dendritic structure, connectivity and activity are affected in mutant animals with abnormal outer retinal development. Together, these studies will increase our understanding of how synaptic inputs are established on RGC dendrites and how perturbation of outer retinal function prior to vision might alter inner retinal structure and function.
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