MODIFICATION OF NATURALISTIC STIMULI FOR RESTORING NATURAL RESPONSES IN OPTOGENETIC ACTIVATION OF RETINAL GANGLION CELLS

Patients suffering from photoreceptor degeneration could potentially regain visual perception through optogenetic gene therapy. This can be achieved by introducing light-gated ion channels to downstream retinal neurons, such as retinal ganglion cells (RGCs). However, with the same stimulus input, optogenetically-activated RGCs often produce firing outputs that significantly differ from outputs driven by photoreceptors. This poses a challenge for restoring vision using optogenetics. To achieve more natural firing patterns, we explored whether modifying the incoming stimulus to optogenetically activate RGCs could induce firing activities that may better resemble the natural outputs as when the original stimulus was presented to photoreceptors. We utilized mice with intact photoreceptors and also with RGCs expressing channelrhodopsin-2 (ChR2) for within-cell comparisons of firing responses under photoreceptor-driven and optogenetically-stimulated conditions. RGC activities were recorded ex-vivo by mounting retinae on planar multi-electrode arrays. We presented naturalistic images and their modified versions to the retinae. Modifications included spatial filtering and light intensity scaling. Photoreceptor-driven responses were obtained by presenting stimuli in low light intensity for exciting photoreceptors without activating ChR2. Strong blue light was then used for activating ChR2, together with pharmacological blockage of upstream synaptic transmission, for obtaining optogenetically-induced responses. My preliminary results aim to characterize the differences between RGC firing activities driven by photoreceptors versus ChR2. We then evaluate whether and how modifying naturalistic stimuli could evoke firing patterns similar to the patterns observed in photoreceptor stimulation in response to the original stimuli. These results could provide insights into the improvement of optogenetic stimulation for vision restoration.