Electrical stimulation alters light responses in mouse retinal ganglion cells.

摘要

Purpose: A goal of visual prosthetics is selective activation of the parallel information channels that are established in the retina. Here, we demonstrate that visual responses of retinal ganglion cells (RGCs) can be altered by electrical stimulation, suggesting stimulation-induced changes affect visual encoding of retinal prosthetic devices. Methods: RGC spiking responses were recorded in vitro from adult (P28-P35) wt (C57BL/6) and degenerating (rd10) mouse retinas, with a multi-electrode array. Visual stimuli were interleaved within an electrical stimulation experiment spanning ~70 minutes of recording time. Each of the 6 visual stimulation blocks consisted of a full-field white flash stimulus (2 s on, 2 s off) cycled 20 times without pause. Epiretinal electrical stimuli consisted of a series of 114 different square wave monophasic voltage pulses of varying voltage and duration (+ 2.5 V to -2.5 V, 0.06 to 5 ms, 5 repetitions each, interpulse interval a?￥5 s). We defined a??nearby responsive cellsa?? as cells with a significant response to at least one pulse and recorded on electrodes at a distance of 200 or 283 ?μm from the stimulating electrode. a??Distant non-responsive cellsa?? did not have significant responses and were recorded on electrodes 300 ?μm away. Visual response characterization was similar to Carcieri et al. (J Neurophysiol. 2003; 90:1704-13). Results: For wt a??nearby responsive cellsa?? (n=108) both on and off visual response amplitudes increased, off latencies decreased slightly, and on response duration increased following electrical stimulation. For rd10 retina (n=122), only off latencies decreased. As a within-experiment control we examined a??distant-non responsive cellsa?? (n= 1267 wt, 931 rd10) to see whether responsiveness changes over time in vitro, independent of electrical stimulation. In these cells we found similar response changes, but the magnitude of wt a??nearby responsive cella?? amplitude changes remained significantly greater than control. We found no significant changes in the on/off index under any conditions - despite large changes for individual cells. Conclusions: Visual response properties can be altered by electrical stimulation. As electrical stimulation influences cellular and/or network responsiveness, it is advisable to incorporate such dynamic network effects into response models for prosthetic retinal stimulation.