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R.J. Jensen, O.R. Ziv, J.F. Rizzo; Thresholds for Direct and Indirect Activation of Ganglion Cells With an Epiretinal Electrode: Effect of Stimulus Duration and Electrode Size . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5048.
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Purpose: To examine the effects of stimulus pulse duration and electrode size on the ability to activate retinal ganglion cells. Our long-term goal is to develop a retinal prosthesis for the blind. Methods: Action potentials of individual ganglion cell axons were recorded extracellularly in superfused adult rabbit retinas in a dimly lit room. Ganglion cells were stimulated electrically with either a 5-µm or 125-µm diameter electrode positioned on the inner surface of the retina over the center of a ganglion cell's receptive field. The return electrode was a Ag/AgCl foil (about 1 cm2 in area) placed on the opposite side of the retina, beneath the sclera. Monophasic, cathodal pulses (0.1 msec or 2 msec in duration) were used. Results: Indirect (i.e. presynaptic) activation of a ganglion cell can be distinguished from direct activation of a ganglion cell by latency of response, number of evoked action potentials, and the effects of pharmacological agents. With both electrodes (5-µm and 125-µm diameter), the current threshold for indirect activation of a ganglion cell was typically higher than for direct activation of a ganglion cell. With the 5-µm electrode, the current threshold for indirect activation of a ganglion cell was on average 37 times higher than for direct activation when using 0.1-msec pulses and was on average 9.3 times higher when using 2-msec pulses. With the 125-µm electrode, the current threshold for indirect activation of a ganglion cell was on average 7.7 times higher than for direct activation when using 0.1-msec pulses and was on average 2.0 times higher when using 2-msec pulses. Conclusions: These results indicate that a short duration current pulse delivered through a small tip microelectrode preferentially stimulates ganglion cells directly, whereas a long duration pulse delivered through a large-tip microelectrode stimulates the inner retina (i.e. ganglion cells) and the deeper retina (i.e. pre-ganglion cell synaptic inputs).
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