Mechanism of oscillatory rhythm of retinal ganglion cells in rd1 mouse retina

Retinal prostheses are being developed to restore vision for the blind with retinal diseases such as retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Among the many issues for prosthesis development, stimulation encoding strategy is one of the most essential electrophysiological issues. The more we understand the differences of retinal circuitry between normal and degenerate retina, the greater it could help decide optimal stimulation parameters for retinal prosthesis. On studying degenerate retina, rd1 mice were used for animal model of RP. Our previous study showed that besides spikes, ~10 Hz oscillatory rhythm (slow wave component) appear in spontaneous firing in rd1 mice retina. This ~10 Hz rhythm still appear in electrically-evoked response of retinal ganglion cells (RGCs) in rd1 mice. In this study, we investigated the mechanism of this oscillatory rhythm. Electrical stimuli were applied via one channel of the 8 x 8 MEA and RGC responses were recorded with the remaining channels. By modulating the current pulse duration and intensity (60 ∼ 1000 μs, 2 ∼ 60 μA, respectively), 20 trains of biphasic square pulse were randomly applied at the rate of 0.25 Hz. We compared the frequency of oscillatory rhythm in poststimulus time histogram (PSTH) before and after various synaptic blockers. With CNQX/AP7 (glutamatergic synapse blocker), the frequency of oscillatory rhythm decreased significantly. Neither strychnine (glycinergic synapse blocker) nor picrotoxin (GABAergic synapse blocker) did affect the oscillatory rhythm. The electrical synapse blockers, heptanol and carbenoxolone showed discrepant effects on the oscillatory rhythm. We are currently performing more experiments with electrical synapse blockers.