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While at least twelve different types of retinal ganglion cells have been characterized by their electrophysiological and morphological properties, the genetic basis underlying this vast array of diversity is largely unknown. I seek to reveal the specific genetic identity of ganglion cell subtypes contributing to the inner retinal circuitry that encodes visual information. To accomplish this, I am combining electrophysiological and viral targeting approaches to correlate functionally identified retinal ganglion cells with their specific genetic markers. I am using patch-clamp recording from ganglion cells that have been fluorescently labeled by highly specific viral and non-viral vectors designed to target neural subclasses. In some cases, these vectors are engineered to enable retrograde transsynaptic tracing of the neural network presynaptic to ganglion cell subtypes. In addition to these path-tracing studies, I am using photosensitive ion channels and pumps that allow for the direct modulation of neural activity with visible light. The combination of neuroengineering and precise genetic targeting to electrophysiologically identified neural subtypes provides a powerful toolbox to increase our understanding of the specific structure/functional relationships that lead to visual function. Using these approaches, I hope to uncover anatomical and functional aspects of inner retinal microcircuitry and to develop a potential inner retinal photostimulation prosthetic for treating photoreceptor based retinal degenerative diseases.

Shown below is a confocal image stack of retinal ganglion and amacrine cells that have been genetically labeled with GFP. The video begins by viewing the inner surface of the retina and flips over to scan through the inner plexifom, ganglion cell, and nerve fiber layers.