Abstract
Abstract: :
Purpose: Several groups around the world are experimenting with retinal prosthetic devices that use electrical stimulation to bypass degenerated retinal photoreceptors. However, not much is known about retinal electrophysiological activity during such stimulation. We investigated this activity by means of patch clamp techniques. Methods: Whole cell patch clamp recordings were obtained from ganglion, amacrine or bipolar cells in the salamander retinal slice preparation. A second patch pipette was positioned immediately adjacent to the ganglion cell side of the slice and used as a stimulating electrode. Results: Long pulses (>5 ms) of cathodic or biphasic electrical stimuli (20–50 mA) evoked inward currents in amacrine, bipolar and ganglion cells. Short current pulses (0.5 ms) failed to evoke a response even when currents were increased to –100 mA. In bipolar cells, epiretinal stimulation evoked large sustained inward currents. In amacrine and ganglion cells, retinal stimulation evoked what appear to be miniature post–synaptic currents. These synaptic currents reversed polarity when the membrane potential was clamped near the equilibrium potential for chloride (∼–20 mV) in both ganglion and amacrine cells and they were blocked by a GABAa/c antagonist, picrotoxin (0.1 mM). Consistent with increased GABAergic inhibition, spontaneous spiking recorded in an amacrine cell while the patch pipette was in cell–attached mode was also inhibited by epiretinal electrical stimulation. Conclusions: Our results show that pulse duration is an important parameter for effective activation of the inner retina by epiretinal stimulation. Epiretinal stimulation appears to be particularly effective at increasing GABAergic inhibition of amacrine and ganglion cells. The sustained inward current evoked by retinal stimulation in bipolar cells is likely to be due to presynaptic calcium currents that would be expected to stimulate glutamate release. The resulting increase in glutamate release from bipolar cells presumably acts on amacrine cells to produce an increased inhibition in the inner retina.
Keywords: electrophysiology: non-clinical • retina: proximal (bipolar, amacrine, and ganglion cells) • retinal degenerations: hereditary