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Shelley I Fried, Perry T Twyford; Retinal Ganglion Cell Responses to Sinusoidal Electrical Stimulation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1841.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal prosthetics strive to restore vision to those who have lost their sight due to retinal degenerative diseases. Existing devices use electrical pulses to stimulate activity in surviving retinal ganglion cells (RGCs) but pulses do not provide a sufficient level of control over elicited neural activity. Recently, sinusoidal waveforms were shown capable of preferential targeting of specific classes of retinal neurons. Here, we extend previous findings to show how individual cell types within each class respond to sinusoidal stimulation.
Cell-attached patch clamping was used to record spikes from retinal ganglion cells in the isolated rabbit retina. A 10 KΩ platinum-iridium stimulating electrode was placed 25 µA above the axon initial segment. Sinusoidal electrical stimuli were applied with frequencies of 5, 10, 25, and 100 Hz, at amplitudes determined by the charge density limits of the electrodes: 4, 9, 18, and 36 µA, respectively.
We found that spikes were elicited at the same phase of each sinusoidal waveform throughout the course of the stimulus. We also observed extremely high levels of similarity in the responses of RGCs that were of the same type although there were differences in the sinusoidal phase during which activity occurred between different cell types. Low frequency sinusoidal stimulation was more charge efficient than high frequency. Experiments with synaptic blockers revealed that low frequencies (5-10 Hz) preferentially stimulated photoreceptors, while high frequencies (25-100 Hz) resulted in direct activation of RGCs.
Our results improve our understanding of how retinal neurons respond to sinusoidal stimuli of varying frequency, Results from this study suggest that it may be much more difficult to activate bipolar cells with sinusoidal stimulation than originally thought, e.g. only the lowest frequencies may be capable. Thus, in the degenerated retina, sinusoidal stimulation may target ganglion cells primarily. The observed differences in the phase at which different ganglion cell types were activated raises the possibility of even further selective targeting although this will need additional investigation.
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