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S. I. Fried, D. K. Freeman, J. F. Rizzo; Low Frequency Sinusoids Avoid Axonal Stimulation With Retinal Prosthetics. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4318.
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© ARVO (1962-2015); The Authors (2016-present)
This work is related to the efforts of the Boston Retinal Implant Project to develop a sub-retinal prosthesis to restore vision to the blind. To improve the quality of vision elicited by retinal prosthetics, we are studying how retinal neurons respond to electric stimulation. Most previous studies have used pulsatile stimulation leaving the response to other stimulus waveforms largely unexplored. Here, we show that low frequency sinusoidal waveforms activate ganglion cells (GCs) strongly but do not activate axons.
Cell-attached patch clamping was used to record spikes from rabbit retinal GCs in the isolated rabbit retina. Electric stimulation was delivered using a small (10kΩ) stimulating electrode placed 25µm above the ganglion cell soma, or 25 µm above the distal axon ~1mm from the soma. Spikes were recorded in response to sinusoidal stimuli of 5 -100Hz. 100 µM Cadmium (Cd++) was applied in some experiments to block all synaptic transmission.
With the stimulating electrode over the soma, low frequency sinusoidal stimulation (LFSS) elicited robust spiking in GCs. This response was eliminated in the presence of Cd++ suggesting LFSS activates presynaptic neurons. LFSS did not elicit activity when the stimulating electrode was moved out over the distal axon. In contrast, cathodal pulses elicited robust spiking for both locations of the stimulating electrode (soma and distal axon); activity at either location was not affected by Cd++ suggesting cathodal pulses activate the GC directly. The ratio of axon to soma threshold for pulses was ~3 for pulses but was >10 for LFSS.
The ability to avoid GC axons by use of low frequency sinusoidal stimulation provides a powerful method to restrict neural activation to a focal region around each stimulating electrode. This may therefore help to improve the quality of elicited percepts, where axonal activation is thought to smear the visual percepts and diminish spatial resolution. In addition, this work opens the possibility that non-pulsatile waveforms may offer finer control over the neurons or neuronal substructures being activated with retinal prosthetics.
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