Comparison of responses of visual cortical neurons in the mouse to intraocular and extraocular electric stimulation of the retina

Retinal implants offered the promise of restoring functional vision to the blind via the delivery of electrical stimulation to the retina. To enhance the efficacy of these devices, stimulation should elicit neural responses that are similar to the responses that occur naturally in the retina as these have the best chance of carrying a robust signal to visual cortex. A corollary of this is that the responses that arise in visual cortical neurons can be used to compare the effectiveness of different stimulation strategies in the retina. Here, we studied how visual cortical neurons in the mouse respond to monophasic cathodal and anodal electric stimulation delivered via a wire electrode positioned on the outer surface of the eye (extraocular) or within the vitreous cavity of the eye (intraocular). Responses of visual cortical neurons were recorded from primary visual cortex on the side contralateral to the stimulatated eye. For both stimulation modalities, response patterns consisted of a brief burst of spikes followed by a 400-500 ms period of inhibition. Both modalities also elicited stronger responses to cathodal stimuli (vs. anodal). The preferential sensitivity to cathodal stimuli is similar to that of epiretinal stimulation (anodal stimuli are more effective with sub-retinal stimulation) suggest the extraocular approach mirrors epiretinal stimulation. Extraocular stimulation also showed some response characteristics that were different from those observed in the retina, e.g., at very strong amplitudes, cathodal and anodal stimulation produced similar responses.