Image modifications reduce differences in natural-image encoding by retinal ganglion cells between natural and optogenetic stimulation

Abstract

Optogenetics is a promising approach for restoring vision after photoreceptor degeneration. Yet, little is known about how responses to natural stimuli in optogenetically treated retinas compare to photoreceptor-driven responses and how any differences might be counteracted by adjusting the stimulation. We here therefore directly compared the encoding of natural images by individual retinal ganglion cells under both conditions in mouse retinas with intact photoreceptors and channelrhodopsin expression in ganglion cells. This showed that channelrhodopsin-evoked responses display reduced dynamic range, more linear encoding of receptive-field activation, and reduced sensitivity to local spatial contrast. We thus devised image modifications, combing thresholding and scaling of pixel intensities with spatial low-pass filtering, and found that applying such modified images for optogenetic stimulation restores original encoding characteristics, yielding responses more similar to the original photoreceptor-evoked activity. These findings may help optimize stimulation of optogenetically treated retinas to achieve more natural vision in future therapeutic applications.