Development of direction selectivity in retina

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PROJECT SUMMARY -- NO CHANGE FROM PARENT AWARD The development of neural circuits involves a rich interplay between molecular cues and neural activity. This is perhaps most well studied in the visual system, where several molecular interactions have been identified as being critical for early establishment of coarse visual maps while both early spontaneous activity called retinal waves prior to eye opening and visual deprivation after eye opening leads to map refinement. We study this question in a direction-selective ganglion cells of the retina. Direction selective ganglion cells respond strongly to an image moving in the preferred direction and weakly to an image moving in the opposite, or null direction. Direction-selective ganglion cells are critical for driving ocular-motor reflexes that stabilize images on the retina as we move through a visual scene as well as for sensing the movement of objects within the visual scene. The preferred directions of direction selective ganglion cells cluster along four directions that align along two optic flow axes, an organization we refer to as the direction selectivity map. The mechanisms that instruct the development of this direction selectivity map are unknown. Here we propose to use a combination of state-of-the-art two-photon calcium imaging, electrophysiology, and transgenic mouse strategies to determine the mechanisms that underlie the development of the direction selectivity maps. In particular, we will determine if neural signaling, either through gap junctions or retinal waves, play a critical role in the formation of these direction selectivity maps. Finally, we will test candidate synaptogenic molecules identified in an RNA-seq screen that may instruct the emergence of the functional inhibitory synapses that underlie direction selective responses.