Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact.
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A common strategy by which developing neurons locate their synaptic partners is through projections to circuit-specific neuropil sublayers. Once established, sublayers serve as a substrate for selective synapse formation, but how sublayers arise during neurodevelopment remains unknown. Here we identify the earliest events that initiate formation of the direction-selective circuit in the inner plexiform layer of mouse retina. We demonstrate that radially-migrating newborn starburst amacrine cells establish homotypic contacts on arrival at the inner retina. These contacts, mediated by the cell-surface protein MEGF10, trigger neuropil innervation resulting in generation of two sublayers comprising starburst-cell dendrites. This dendritic scaffold then recruits projections from circuit partners. Abolishing MEGF10-mediated contacts profoundly delays and ultimately disrupts sublayer formation, leading to broader direction tuning and weaker direction-selectivity in retinal ganglion cells. Our findings reveal a mechanism by which differentiating neurons transition from migratory to mature morphology, and highlight this mechanism's importance in forming circuit-specific sublayers.
Published Version (Please cite this version)
Ray, Thomas A, Suva Roy, Christopher Kozlowski, Jingjing Wang, Jon Cafaro, Samuel W Hulbert, Christopher V Wright, Greg D Field, et al. (2018). Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact. eLife, 7. 10.7554/elife.34241 Retrieved from https://hdl.handle.net/10161/16624.
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My laboratory studies how the retina processes visual scenes and transmits this information to the brain. We use multi-electrode arrays to record the activity of hundreds of retina neurons simultaneously in conjunction with transgenic mouse lines and chemogenetics to manipulate neural circuit function. We are interested in three major areas. First, we work to understand how neurons in the retina are functionally connected. Second we are studying how light-adaptation and circadian rhythms alter visual processing in the retina. Finally, we are working to understand the mechanisms of retinal degenerative conditions and we are investigating potential treatments in animal models.
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