Encoding visual information in retinal ganglion cells with prosthetic stimulation

Abstract

Retinal prostheses aim to restore functional vision to those blinded by outer retinal diseases using electric stimulation of surviving retinal neurons. The ability to replicate the spatiotemporal pattern of ganglion cell spike trains present under normal viewing conditions is presumably an important factor for restoring high-quality vision. In order to replicate such activity with a retinal prosthesis, it is important to consider both how visual information is encoded in ganglion cell spike trains, and how retinal neurons respond to electric stimulation. The goal of the current review is to bring together these two concepts in order to guide the development of more effective stimulation strategies. We review the experiments to date that have studied how retinal neurons respond to electric stimulation and discuss these findings in the context of known retinal signaling strategies. The results from such in vitro studies reveal the advantages and disadvantages of activating the ganglion cell directly with the electric stimulus (direct activation) as compared to activation of neurons that are presynaptic to the ganglion cell (indirect activation). While direct activation allows high temporal but low spatial resolution, indirect activation yields improved spatial resolution but poor temporal resolution. Finally, we use knowledge gained from in vitro experiments to infer the patterns of elicited activity in ongoing human trials, providing insights into some of the factors limiting the quality of prosthetic vision.

Figure 1. Illustration of Visual Percepts Induced by Prosthetic Stimulation

Simulations of how an image could be constructed by eliciting individual phosphenes of varying brightness. The simulation was performed by dividing the original photo into approximately 100, 700, or 2,500 segments (simulating arrays with varying numbers of electrodes) and then averaging the luminance that falls within that segment in the original photo. Each segment is then multiplied by a 2-D Gaussian filter to reproduce the circular shape of each phosphene.

Figure 2. Direct versus Indirect Activation of Ganglion Cells with Electric Stimulation

The retina contains five major neuronal types: photoreceptors (P), horizontal cells (H), bipolar cells (B), amacrine cells (A), and ganglion cells (G). Direct activation elicits ganglion cell spiking as a result of the electric stimulus acting directly on the ganglion cell. Indirect activation elicits ganglion cells spiking when the electric stimulus acts on presynaptic neurons, producing a synaptic release at both excitatory (gray) and inhibitory (black) synapses. Ganglion cells receive excitatory and inhibitory synaptic input from bipolar and amacrine cells, respectively.

Figure 3. Retinal Ganglion Cell Spiking Responses to Direct versus Indirect Activation

Spikes were recorded from a rabbit retinal ganglion cell in response to epi-retinal stimulation with a 10kΩ Pt-Ir electrode. a. A cathodic pulse of 0.2ms duration was applied, followed by a 10ms delay, and then an anodal pulse. This delay was used in order to reveal the elicited spike (arrow) embedded in the stimulus artifact. This spike was elicited by direct activation (one-spike-per-pulse). b. A 1ms duration pulse (cathodic-first, with zero delay between cathodal and anodal phases) elicits a burst of spikes (asterisks) through indirect (i.e. synaptic) activation of the ganglion cell (one-burst-per-pulse). In response to this pulse, a spike was also elicited through direct activation (arrow).

Figure 4. Temporal Resolution for Direct versus Indirect Activation

Spikes were recorded from two rabbit retinal ganglion cells in response to epi-retinal stimulation with a 10kΩ Pt-Ir electrode. a. Direct activation with 0.2ms pulses delivered at 225Hz elicits one-spike-per-pulse, where spikes (asterisks) are phase-locked to the cathodal phase. b. Indirect activation elicits one-burst-per-pulse at 8Hz, but the number of spikes per burst decreases dramatically after the first pulse due to desensitization. The number of spikes per pulse is given above the response to each pulse.