PT - JOURNAL ARTICLE AU - Lauren E. Grosberg AU - Karthik Ganesan AU - Georges A. Goetz AU - Sasidhar Madugula AU - Nandita Bhaskar AU - Victoria Fan AU - Peter Li AU - Paweł Hottowy AU - Władysław Dabrowski AU - Alexander Sher AU - Alan M. Litke AU - Subhasish Mitra AU - E.J. Chichilnisky TI - Selective activation of ganglion cells without axon bundles using epiretinal electrical stimulation AID - 10.1101/075283 DP - 2016 Jan 01 TA - bioRxiv PG - 075283 4099 - http://biorxiv.org/content/early/2016/09/15/075283.short 4100 - http://biorxiv.org/content/early/2016/09/15/075283.full AB - Epiretinal prostheses for treating blindness activate axon bundles, causing large, arc-shaped visual percepts that limit the quality of artificial vision. Improving the function of epiretinal prostheses therefore requires understanding and avoiding axon bundle activation. This paper introduces a method to detect axon bundle activation based on its electrical signature, and uses the method to test whether epiretinal stimulation can directly elicit spikes in individual retinal ganglion cells without activating nearby axon bundles. Combined electrical stimulation and recording from isolated primate retina were performed using a custom multi-electrode system (512 electrodes, 10 µm diameter, 60 µm pitch). Axon bundle signals were identified by their bi-directional propagation, speed, and increasing amplitude as a function of stimulation current. The threshold for bundle activation varied across electrodes and retinas, and was in the same range as the threshold for activating retinal ganglion cells near their somas. In the peripheral retina, 45% of electrodes that activated individual ganglion cells (17% of all electrodes) did so without activating bundles. This permitted selective activation of 21% of recorded ganglion cells (7% of all ganglion cells) over the array. In the central retina, 75% of electrodes that activated individual ganglion cells (16% of all electrodes) did so without activating bundles. The ability to selectively activate a subset of retinal ganglion cells without axon bundles suggests a possible novel architecture for future epiretinal prostheses.New & Noteworthy Large-scale multi-electrode recording and stimulation were used to test how selectively retinal ganglion cells can be electrically activated without activating axon bundles. A novel method was developed to identify axon activation based on its unique electrical signature, and used to find that a subset of ganglion cells can be activated at single-cell, single-spike resolution without producing bundle activity, in peripheral and central retina. These findings have implications for the development of advanced retinal prostheses.