Retinal prostheses are being developed to restore vision for those with retinal diseases such as retinitis pigmentosa or age-related macular degeneration. Since neural prostheses depend upon electrical stimulation to control neural activity, optimal stimulation parameters for successful encoding of visual information are one of the most important requirements to enable visual perception. In this paper, we focused on retinal ganglion cell (RGC) responses to different stimulation parameters and compared threshold charge densities in wild-type and rd1 mice. For this purpose, we used in vitro retinal preparations of wild-type and rd1 mice. When the neural network was stimulated with voltage- and current-controlled pulses, RGCs from both wild-type and rd1 mice responded; however the temporal pattern of RGC response is very different. In wild-type RGCs, a single peak within 100 ms appears, while multiple peaks (approximately four peaks) with ∼ 10 Hz rhythm within 400 ms appear in RGCs in the degenerated retina of rd1 mice. We find that an anodic phase-first biphasic voltage-controlled pulse is more efficient for stimulation than a biphasic current-controlled pulse based on lower threshold charge density. The threshold charge densities for activation of RGCs both with voltage- and current-controlled pulses are overall more elevated for the rd1 mouse than the wild-type mouse. Here, we propose the stimulus range for wild-type and rd1 retinas when the optimal modulation of a RGC response is possible.
The results suggest that pulse amplitude modulation is a feasible means of implementing a stimulation strategy for retinal prostheses, despite the marked change in the physiological properties of RGCs in degenerated retinas.
For successful visual perception by visual prosthesis using electrical stimulation, it is essential to develop an effective stimulation strategy based on understanding of retinal ganglion cell (RGC) responses to electrical stimulation. W e studied RGC responses to repetitive electrical stimulation pulses to develop a stimulation strategy using stimulation pulse frequency modulation. Retinal patches of photoreceptor-degenerated retinas from rd1 mice were attached to a planar multi-electrode array (MEA) and RGC spike trains responding to electrical stimulation pulse trains with various pulse frequencies were observed. RGC responses were strongly dependent on inter-pulse interval when it was varied from 500 to 10 ms. Although the evoked spikes were suppressed with increasing pulse rate, the number of evoked spikes were > 60% of the maximal responses when the inter-pulse intervals exceeded 100 ms. Based on this, we investigated the modulation of evoked RGC firing rates while increasing the pulse frequency from 1 to 10 pulses per second (or Hz) to deduce the optimal pulse frequency range for modulation of RGC response strength. RGC response strength monotonically and linearly increased within the stimulation frequency of 1∼ 9 Hz. The results suggest that the evoked neural activities of RGCs in degenerated retina can be reliably controlled by pulse frequency modulation, and may be used as a stimulation strategy for visual neural prosthesis.
PURPOSE.To restore visual function via the prosthetic stimulation of retina, visual information must be properly represented in the electrically evoked neural activity of retinal ganglion cells (RGCs). In this study, the RGC responses in photoreceptor-degenerated retinas were shown to actually encode temporal information on visual input when they were stimulated by biphasic pulse trains with amplitude modulation. METHODS. Multiple RGC spike trains were recorded from rd1 mouse retinal patches mounted on planar microelectrode arrays while being stimulated by pulse trains with amplitudes modulated by the intensity variation of a natural scene. To reconstruct the time series of pulse train amplitudes from the evoked RGC activity, spike train decoding was performed. The accuracy of decoding-that is, the similarity between the original and decoded pulse amplitudes-was observed, to evaluate the appropriateness of the stimulation. RESULTS. The response strengths of the RGCs could be successfully modulated when the pulse amplitude was varied between 2 and 20 A. When the amplitude modulation range and pulse rates were determined elaborately, the temporal profile of the intensity could be successfully decoded from RGC spike trains, although abnormal oscillatory background rhythms (ϳ10 Hz) were consistently present in the rd1 spike activity. CONCLUSIONS. The results extend previous findings on the possibility of visual information encoding by electrical stimulation of normal retinas to stimulate degenerated retinas, in which neural activity is significantly altered. This supports the feasibility of encoding of temporal information by retinal prostheses. (Invest Ophthalmol Vis Sci. 2011;52:6271-6278 For the successful restoration of visual function, neural responses evoked by electrical stimulation should accurately represent spatiotemporal information on visual input. We have recently shown that in the normal retina, this is feasible through amplitude modulation of pulse trains when the parameters of stimulation are carefully selected.9,10 However, it has been recognized that RGC activity is significantly altered in the degenerated retina due to changes in synaptic properties 11,12 ; thus, abnormal rhythmic oscillation is present in both spontaneous and stimulated neural activity. Because this rhythmic oscillation does not originate from external visual inputs, it may disturb the representation and transmission of visual information by RGC activity in blind persons. Thus, visual information encoded by prosthetic electrical stimulation should be observed carefully in the degenerated retina.Quantitative investigation into information encoding by neuronal networks can be performed by spike train decoding, which consists of estimating (decoding) quantitative information encoded in neuronal activity. Typical applications include the study of fundamental visual information encoding characteristics of neuronal populations 13,14 and the control of brain-machine interfaces. 15 In the present study, we sought to determine whether it ...
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