Response of Mouse Visual Cortical Neurons to Electric Stimulation of the Retina.

Abstract

Retinal prostheses strive to restore vision to the blind by electrically stimulating the neurons that survive the disease process. Clinical effectiveness has been limited however, and much ongoing effort is devoted toward the development of improved stimulation strategies, especially ones that better replicate physiological patterns of neural signaling. Here, to better understand the potential effectiveness of different stimulation strategies, we explore the responses of neurons in the primary visual cortex to electric stimulation of the retina. A 16-channel implantable microprobe was used to record single unit activities in vivo from each layer of the mouse visual cortex. Layers were identified by electrode depth as well as spontaneous rate. Cell types were classified as excitatory or inhibitory based on their spike waveform and as ON, OFF, or ON-OFF based on the polarity of their light response. After classification, electric stimulation was delivered via a wire electrode placed on the surface of cornea (extraocularly) and responses were recorded from the cortex contralateral to the stimulated eye. Responses to electric stimulation were highly similar across cell types and layers. Responses (spike counts) increased as a function of the amplitude of stimulation, and although there was some variance across cells, the sensitivity to amplitude was largely similar across all cell types. Suppression of responses was observed for pulse rates ≥3 pulses per second (PPS) but did not originate in the retina as RGC responses remained stable to rates up to 5 PPS. Low-frequency sinusoids delivered to the retina replicated the out-of-phase responses that occur naturally in ON vs. OFF RGCs. Intriguingly, out-of-phase signaling persisted in V1 neurons, suggesting key aspects of neural signaling are preserved during transmission along visual pathways. Our results describe an approach to evaluate responses of cortical neurons to electric stimulation of the retina. By examining the responses of single cells, we were able to show that some retinal stimulation strategies can indeed better match the neural signaling patterns used by the healthy visual system. Because cortical signaling is better correlated to psychophysical percepts, the ability to evaluate which strategies produce physiological-like cortical responses may help to facilitate better clinical outcomes.