Abstract
Purpose:
Recent clinical reports indicate that stimulation rates in the range of 5-7 Hz are most preferable to users of the retinal prosthetic. This is surprising given that previous in-vitro studies suggest that such rates have a diminishing effect on the response to network-mediated activation in retinal ganglion cells (RGCs). This discrepancy raises questions about the cell type dependence of network-mediated responses to repetitive stimulation. If some RGC types have considerably different behaviors in response to repetitive stimulation from others, the possibility exists that not all types of RGCs contribute equally to psychophysical percepts. Thus a more systematic investigation into the responses to repetitive stimulation might help to explain specific clinical observations. Here, we measured the network-mediated responses elicited by repetitive electric stimulation in RGCs as a function of stimulation rate and explored differences across cell types.
Methods:
Cell-attached patch clamp was used to record spikes from RGCs in the isolated rabbit retina. RGCs were classified as ON or OFF cells by their response to stationary flashes. After cell type classification, a monophasic half-sinusoidal wave (duration of 4ms, corresponds to half period of single 125Hz sine wave, amplitude of -100µA) was presented to targeted RGCs; five consecutive stimuli were delivered with various inter-stimulus intervals. We recorded the spiking activity in 8 ON cells, and 9 OFF cells.
Results:
The electric responses of RGCs to repetitive stimuli had clear distinctions between ON and OFF types. The responses of all OFF cells (n=9/9) showed the reduced sensitivity to subsequent stimuli as reported in previous studies. In contrast, the responses of ON cells exhibited formerly unreported characteristics; the new stimulus suppressed all pending responses to any previous stimuli and initiated its own response that is highly similar to the response from a single stimulus in isolation. This unique 'reset' behavior was observed exclusively and always (n=8/8) in ON cells. Also, these contrasts between ON and OFF cells created different temporal properties of network-mediated responses to repetitive stimuli in various stimulation rates.
Conclusions:
Our results with repetitive stimulation reveal fundamental differences between responses in ON and OFF types of RGCs, offering insights to psychophysical results.