Adjusting the parameters of electrical stimulation of retinal ganglion cells to reduce neural adaptation and improve efficacy of retinal prostheses

© 2018 Dr. Artemio Soto-BrecedaRetinal prostheses aim to provide visual percepts through electrical stimulation of the retina to blind people affected by diseases caused by photoreceptor degeneration. Two challenges presented by current devices are a lack of selectivity in the activation of retinal ganglion cells (RGCs) and neural adaptation in the retina, which is believed to be the cause of fading—an effect where artificially produced percepts disappear over a short period of time, despite continuous stimulation of the retina. We aim to (1) understand the neural adaptation generated in RGCs during electrical stimulation, (2) obtain the preferred stimulation parameters (waveform) of each morphological class of RGCs and (3) use the preferred waveform of each morphological class to selectively activate different neurons. RGCs have been classified by morphology into 4 main groups: A, B, C and D. We performed an spike-triggered covariance (STC) analysis on the responses of 44 RGCs to extracellular electrical white noise and 43 RGCs to intracellular white noise. We then recovered their temporal electrical receptive fields (tERF), or waveform. A number of RGCs were stimulated with all the previously recovered waveforms to test the efficacy of each waveform on each other. The waveform recovered from the responses to intracellular stimulation have shown that RGCs can be classified into their respective morphological types by using a K-means clustering algorithm. Extracellular stimulation did not result in waveforms with a clear correlation between clusters and morphological classes. Cells from B and D morphological types had lower thresholds when stimulated with the waveform recovered from cells in the same morphological class. A-RGCs on the contrary, did not seem to share the same temporal features in their waveform with other A-type neurons. Further studies involving a larger data set might determine whether the waveform could preferentially stimulate cells from a specific morphological class. Current visual prostheses use electrical pulses with fixed frequencies and amplitudes modulated over hundreds of milliseconds to stimulate the retina. However, in nature, neuronal spiking occurs with stochastic timing, hence the information received naturally from other neurons by RGCs is irregularly timed. We used a single epiretinal electrode to stimulate and compare rat RGC responses to stimulus trains of biphasic pulses delivered at regular and random inter-pulse intervals (IPI), the latter taken from an exponential distribution. Our observations suggest that stimulation with random IPIs result in lower adaptation rates than stimulation with constant IPIs at frequencies of 50 Hz and 200 Hz. We also found a high proportion of lower amplitude action potentials, or spikelets. The spikelets were more prominent at high stimulation frequencies (50 Hz and 200 Hz) and were less susceptible to adaptation, but it was not clear if they propagated along the axon. Using random IPI stimulation in retinal prostheses reduces the decay of RGCs and this could potentially reduce fading of electrically induced visual perception