Response variability to high rates of electric stimulation in retinal ganglion cells.

To improve the quality of prosthetic vision, it is important to understand how retinal neurons respond to electric stimulation. Previous studies present conflicting reports as to the maximum rate at which retinal ganglion cells can "follow" pulse trains, i.e., generate one spike for each pulse of the train. In the present study, we measured the response of 5 different types of rabbit retinal ganglion cells to pulse trains of 100-700 Hz. Surprisingly, we found significant heterogeneity in the ability of different types to follow pulse trains. For example, brisk transient (BT) ganglion cells could reliably follow pulse rates up to 600 pulses per second (PPS). In contrast, other types could not even follow rates of 200 PPS. There was additional heterogeneity in the response patterns across those types that could not follow high-rate trains. For example, some types generated action potentials in response to approximately every other pulse, whereas other types generated one spike per pulse for a few consecutive pulses and then did not generate any spikes in response to the next few pulses. Interestingly, in the types that could not follow high-rate trains, we found a second type of response: many pulses of the train elicited a biphasic waveform with an amplitude much smaller than that of standard action potentials. This small waveform was often observed following every pulse for which a standard spike was not elicited. A possible origin of the small waveform and its implication for effective retinal stimulation are discussed.

Axonal sodium-channel bands shape the response to electric stimulation in retinal ganglion cells.

Electric stimulation of the retina reliably elicits light percepts in patients blinded by outer retinal diseases. However, individual percepts are highly variable and do not readily assemble into more complex visual images. As a result, the quality of visual information conveyed to patients has been quite limited. To develop more effective stimulation methods that will lead to improved psychophysical outcomes, we are studying how retinal neurons respond to electric stimulation. The situation in the retina is analogous to other neural prosthetic applications in which a better understanding of the underlying neural response may lead to improved clinical outcomes. Here, we determined which element in retinal ganglion cells has the lowest threshold for initiating action potentials. Previous studies suggest multiple possibilities, although all were within the soma/proximal axon region. To determine the actual site, we measured thresholds in a dense two-dimensional grid around the soma/proximal axon region of rabbit ganglion cells in the flat mount preparation. In directionally selective (DS) ganglion cells, the lowest thresholds were found along a small section of the axon, about 40 microm from the soma. Immunochemical staining revealed a dense band of voltage-gated sodium channels centered at the same location, suggesting that thresholds are lowest when the stimulating electrode is closest to the sodium-channel band. The size and location of the low-threshold region was consistent within DS cells, but varied for other ganglion cell types. Analogously, the length and location of sodium channel bands also varied by cell type. Consistent with the differences in band properties, we found that the absolute (lowest) thresholds were also different for different cell types. Taken together, our results suggest that the sodium-channel band is the site that is most responsive to electric stimulation and that differences in the bands underlie the threshold differences we observed.