Circuit maturation and function in postnatal primate retina

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PROJECT SUMMARY/ABSTRACT Establishment of functional neuronal circuits within the retina relies on a period of postnatal maturation. Our knowledge of this developmental period is restricted to information from non-primate model systems. This project aims to determine the progression of postnatal maturation across two divergent primary output pathways in the primate retina– ON and OFF parasol retinal ganglion cells (RGCs) - by correlating functional activity of RGCs obtained by single cell electrophysiology to expression profiles of synaptic markers and the ultrastructural synaptic connectivity map underlying neuronal function. Our studies will compare observations from three postnatal timepoints before visual function and circuit maturation reaches adult profiles. In Aim 1 we will determine the postnatal development of light evoked functional responses of ON and OFF parasol RGCs including spike output across luminance levels and intrinsic electrical properties. In Aim 2 we will determine the postnatal development of excitatory and inhibitory synaptic inputs onto ON and OFF parasol RGCs that regulate their responses, including expression profiles of constituent pre- and postsynaptic proteins and the 3D ultrastructural organization of synaptic inputs. Our findings will provide the first insights into the early stages of postnatal functional maturation across key parallel pathways (ON and OFF parasol RGCs) in the primate retina, thereby addressing the current knowledge gap about the process of postnatal circuit and synapse maturation during primate retinal development. Our observations will also reveal if functionally divergent retinal pathways mature at similar or disparate rates and identify substrates that cause developmental visual deficits. Moreover, our findings will provide important baseline information about functional maturation of primate retinal neurons critical for developing lab grown human stem cell derived retinas that mimic functional properties of primate retina to model and treat a wide range of retinal degenerative diseases.