Responses of ganglion cells to repetitive electrical stimulation of the retina

Abstract

Retinal ganglion cells (RGCs) can be activated electrically either directly or indirectly (via the retinal neural network). Previous studies have shown that RGCs can follow high stimulus rates (> or = 200 pulses s(-1)) when directly activated. In the present study, we investigated how well RGCs can follow repetitive stimulation of the neural network. We studied the responses (spike activity) of RGCs in isolated rabbit retina to stimulation with paired pulses applied at different interpulse intervals and trains of pulses applied at different frequencies. We found that the response amplitude of a RGC to a current pulse applied soon (< or = 400 ms) after a preceding current pulse is diminished. This depression in response amplitude became greater as the interval between pulses became shorter. At an interpulse interval of 15 ms (shortest tested), the response amplitude to the second current pulse was reduced on average 94%. When a train of ten stimulus pulses was applied, further depression was observed, particularly at high stimulation frequencies. The depression with each successive pulse was relatively moderate compared to the depression to the second pulse. The results of this study have implications for the design of electrical stimulation strategies in a retinal prosthesis.

Electrically-evoked Neural Activities of rd1 Mice Retinal Ganglion Cells by Repetitive Pulse Stimulation

“…Changes in neural activities responding to repetitive stimulation by pulse trains applied with various inter-pulse intervals were observed. The results showed that the response strength of the RGCs of rd1 mice could be effectively modulated by inter-pulse interval, and, thus, by pulse frequency, as previously shown for normal retina (Jensen and Rizzo, 2007). An optimal range for the pulse frequency modulation was presently determined by observing the frequency ranges where the RGC response strength was increased monotonically by pulse frequency.…”

“…RGC responses to repetitive stimulation pulses have been reported for normal retinas (Fried et al, 2006;Sekirnjak et al, 2006;Jensen and Rizzo, 2007;Ahuja et al, 2008). However, few reports have described RGC responses of degenerated retinas evoked by repetitive pulse stimulations.…”

“…Perception of simple visual patterns or phosphenes have been reported from clinical trials of human blind patients (Veraart et al, 1998;Humayun et al, 1999;Humayun et al, 2003;Rizzo et al, 2003;Hornig et al, 2005). Based on an in-vitro model of retinal implant that consists of retinal patches mounted on a planar multielectrode array (MEA), several studies on the properties of electrically-evoked firing of retinal ganglion cells (RGCs) have increased the basic knowledge required to determine effective methods of visual stimulation (Stett et al, 2000;Jensen and Rizzo, 2007;Ryu et al, 2009b). Recently, we showed that RGC response strength can be effectively controlled by amplitude modulation of stimulation pulse trains so that light intensity variation can be encoded within the RGC spike trains (Ryu et al, 2009b).…”

High-Resolution Electrical Stimulation of Primate Retina for Epiretinal Implant Design

“…Such stimulation attempts use much larger electrodes (125-500 m) and/or long-duration stimulation pulses (ϳ1 ms), and result in multiple evoked spikes at long latencies (ϳ10 ms). With these stimulation configurations, spike thresholds are typically much higher than the direct-activation values reported in this study (Jensen et al, 2003;Suzuki et al, 2004;Guven et al, 2005;Jensen and Rizzo, 2007;Ye and Goo, 2007). Results from the present study are most comparable with recently published reports of epiretinal stimulation that activated ganglion cells directly by using small electrodes and short pulses: 0.05-0.31 mC/cm 2 for 40 m disk electrodes in frog retina (Kuras et al, 2004), 0.14 -0.25 mC/cm 2 for 30 m cone-shaped electrodes in rabbit retina (Fried et al, 2006), and 0.02-0.20 mC/ cm 2 for 8 -12 m disk electrodes in rat retina (Sekirnjak et al, 2007).…”

“…Several groups have targeted deeper retinal neurons (bipolar cells and photoreceptors) for epiretinal stimulation, which activates ganglion cells through the retinal neural network and thus stimulates them indirectly (Jensen and Rizzo, 2007). Such stimulation attempts use much larger electrodes (125-500 m) and/or long-duration stimulation pulses (ϳ1 ms), and result in multiple evoked spikes at long latencies (ϳ10 ms).…”