Non-rectangular waveforms are more charge-efficient than rectangular one in eliciting network-mediated responses of ON type retinal ganglion cells

摘要

Objective. For individuals blinded by outer retinal degenerative diseases, retinal prostheses would be a promising option to restore sight. Unfortunately, however, the best performance of existing devices is still far removed from normal vision. One possible reason for the shortcoming is thought to be suboptimal stimulation conditions such as the waveform shape of electric stimulus. In this study, we explored the effects of varying waveforms on network-mediated responses arising in retinal ganglion cells (RGCs). Approach. We used a cell-attached patch clamp technique to record RGC spiking activities in the isolated mouse retina. ON alpha RGCs were targeted by soma size and their light responses to stationary spot flashes. Spiking in targeted RGCs was measured in response to an epiretinally-delivered cathodal current pulse in four waveforms: rectangular, center triangular, increasing and decreasing ramp shapes. Each waveform was tested at three durations (20, 10, and 5 ms) with adjusted amplitude for a range of total charges (50-400 nC). Main results. ON alpha RGCs always generated two bursts of spikes in responses to all stimuli conditions we tested. However, at a given charge, effects of differing waveforms were distinct in the two bursts. For the first burst, the increasing ramp was most effective among the four waveforms (p < 0.05 for all pairwise comparisons with other waveforms). For example, in responses arising from 20 ms-long stimuli, the increasing ramp evoked ～44% more spikes on average than the rectangular shape which is the typical choice of neural stimulation. Also, the rectangular stimulus evoked the weakest response in the delayed burst arising from pulses of every duration. For instance, 20 ms-long stimuli in the three non-rectangular waveforms showed ～23% or more increment in spike counts compared to response arising from the rectangular one; but there was no statistical difference in response magnitudes across the non-rectangular waveforms. Significance. Although the rectangular waveform has been primarily used in retinal prostheses our results indicate that rectangular stimulus is not optimal for network-mediated responses of ON alpha RGCs. Instead, non-rectangular waveforms evoke stronger responses at a given charge, indicating higher charge-efficiency. Therefore, non-rectangular waveforms are expected to enhance clinical efficacy of retinal prostheses.