High frequency electric stimulation of retinal neurons elicits physiological signaling patterns

The effectiveness of retinal prosthetics will depend on their ability to elicit patterns of neural activity that can be recognized by the visual cortex. While conventional short-duration pulses activate retinal neurons effectively, many nearby neurons are thought to respond similarly to a given pulse train — a situation that is non-physiological. Use of pulse trains delivered at rates > 1000 pulses per second (PPS) in cochlear prosthetics help to avoid phase-locked responses but have not been evaluated in the retina; here, we explored the response to trains of 2000 PPS. We found that ganglion cells respond robustly to these stimuli but that the properties of the response were highly sensitive to stimulus amplitude. At low amplitudes the response patterns were burst-like while at higher amplitudes elicited spikes had intervals that were more uniform. Because burst responses were insensitive to synaptic blockers, our results suggest that they arise from direct activation. This was surprising because previous studies indicated that burst responses arise only through indirect activation. Thus, our results suggest multiple mechanisms of burst creation may exist. Further, histograms of interspike intervals revealed that the response properties were different in different types of ganglion cells. While further testing is needed, the ability to create different patterns of activity in different types of ganglion cells raises the possibility that more natural spike patterns can be created.