Inner retinal mechanisms engaged by retinal electrical stimulation

PURPOSE. Retinal prosthetic devices are being developed to bypass degenerated retinal photoreceptors by directly activating retinal neurons with electrical stimulation. However, little is known about retinal activity during such stimulation. METHODS. Whole cell patch-clamp recordings were obtained from ganglion and bipolar cells in the salamander retinal slice preparation. A stimulating electrode was positioned at the vitreal surface of the slice. RESULTS. Brief pulses of cathodic current evoked transient inward currents in ganglion cells arising from action potentials. Longer pulses (>5 milliseconds) also evoked sustained inward currents in ganglion cells that appeared synaptic in origin because, unlike transient currents, sustained currents were blocked by inhibiting synaptic transmission with Cd²⁺. These synaptic currents reversed around E_Cl and were blocked by picrotoxin, strychnine, or both, suggesting they were mediated by GABA _a/c and glycine receptors. Synaptic currents were also blocked by the NMDA antagonist MK801 and the KA/AMPA antagonist NBQX, suggesting that epiretinal stimulation evoked glutamate release from bipolar cells, which in turn stimulated the release of GABA and glycine from amacrine cells. Sustained currents were also evoked by epiretinal stimulation in bipolar cells. These currents reversed near E_Cl and were blocked by picrotoxin, suggesting they arose from GABA_a/c receptors. CONCLUSIONS. Pulse duration is an important parameter for effective activation of the inner retina by epiretinal stimulation. Brief pulses evoke action potentials only in ganglion cells. However, longer pulses also evoke sustained synaptic currents by stimulating glutamate release from bipolar cell terminals, which, in turn, evokes the release of GABA and glycine from amacrine cells.