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Wiring up visual circuits: Interplay between gene expression and spontaneous and experience-dependent activity

Final Report Summary - WIRINGVISION (Wiring up visual circuits: Interplay between gene expression and spontaneous and experience-dependent activity)

Classic studies proposed that genetically-encoded programs and spontaneous activity play complementary but independent roles in the development of neural circuits. More recent evidence, however, suggested that these two mechanisms could interact extensively, with spontaneous activity affecting the expression and function of guidance molecules at early developmental stages. Results in our laboratory verify the notion that spontaneous activity does not affect neuronal identity specification, axon pathfinding or gross topography during the assembly of the visual circuit. Our experiments argue for the dissociation of spontaneous activity from hard-wired developmental programs in early phases of neural circuit assembly, and support a subsequent role for spontaneous activity in fine-tune axon pruning once axon terminals have reached their correct topographic position in the target tissues. Using a new transgenic mouse line with altered retinal activity generated in our laboratory, we have searched for specific genes involved in the refinement process in a gene-wide unbiased manner and have found an NMDA receptor highly downregulated in the mutant mice, that could be important in mediating retinal spontaneous activity. We are currently performing functional experiments to elucidate the function of this receptor in this process.
For the second aim of the project we have generated a transgenic mouse line with an increased number of ipsilateral visual axons and we are currently analyzing whether these mice have the capacity of rewiring their thalamocortical projections, expand the binocular visual cortical region and improve binocular vision. If this is the case, these results would demonstrate that a single gene mutation during development could lead to the complete rewiring of a circuit and the emergence of a new sensory capacity.