Electrical stimulation of different retinal components and the effect of asymmetric pulses

Background: High resolution electrical stimulation of neural tissue is a fundamental challenge in applications such as deep brain stimulation and artificial vision. In artificial vision, achieving and validating local selective epi-retinal stimulation of different layers in the retina is particularly challenging owing to plurality of retinal cell types and delocalized wiring. Results: Strong selectivity and non-localized responses to epi-retinal stimulation, over a wide range of realistic stimulation parameters, was achieved and validated using asymmetric pulses. New method: The reported method consists of multi electrode array (MEA) stimulation and recording from a developing chick retina combined with calcium imaging. Data show direct and indirect neuronal activation in the chick retina model. In particular, axonal activation, orientation and conduction velocity are derived, and the non-local nature of the responses to direct axonal stimulation is demonstrated. Comparison with existing methods: Some of the previous research with mammalian retinas demonstrated local responses around the stimulating electrode, revealing little as to axonal activation. Recent studies showed activation along the nerve fibers and studied the effect of pulse duration to improve stimulation localization (Twyford and Fried, 2016; Weitz et al., 2015). The chick retina offers a straight forward mapping of axonal activation. Here we demonstrate that the chick retina, combined with MEA recording and stimulation along with calcium imaging is a powerful tool to study retinal activation and in particular the effect of asymmetry on axonal activation. Conclusions: MEA recording and stimulation from the chick retina is exceptionally powerful in distinguishing between direct and indirect responses. This method facilitates comparison between different stimulation strategies. We show that asymmetric electrical stimulations allow control over the intensity of direct activation. (C) Published by Elsevier B.V.