For successful visual perception by visual prosthesis using electrical stimulation, it is essential to develop an effective stimulation strategy based on understanding of retinal ganglion cell (RGC) responses to electrical stimulation. We studied RGC responses to repetitive electrical stimulation pulses to develop a stimulation strategy using stimulation pulse frequency modulation. Retinal patches of photoreceptor-degenerated retinas from rd1 mice were attached to a planar multi-electrode array (MEA) and RGC spike trains responding to electrical stimulation pulse trains with various pulse frequencies were observed. RGC responses were strongly dependent on inter-pulse interval when it was varied from 500 to 10 ms. Although the evoked spikes were suppressed with increasing pulse rate, the number of evoked spikes were > 60% of the maximal responses when the inter-pulse intervals exceeded 100 ms. Based on this, we investigated the modulation of evoked RGC firing rates while increasing the pulse frequency from 1 to 10 pulses per second (or Hz) to deduce the optimal pulse frequency range for modulation of RGC response strength. RGC response strength monotonically and linearly increased within the stimulation frequency of 1-9 Hz. The results suggest that the evoked neural activities of RGCs in degenerated retina can be reliably controlled by pulse frequency modulation, and may be used as a stimulation strategy for visual neural prosthesis.
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