In vitro assessment of the differences in retinal ganglion cell responses to intra- and extracellular electrical stimulation

To compare responses of retinal ganglion cells (RGCs) to intracel- lular and extracellular electrical stimulation of varying frequency and amplitude. Approach In vitro patch clamp was used to record the responses of RGCs to si- nusoidal current stimulation of varying frequency and amplitude. The results were simulated using the Neuron software package. Main results The stimulation fre- quency yielding the greatest response was higher for extracellular stimulation com- pared to intracellular stimulation in the same cells (256 Hz versus 64 Hz). In fact, at the high end of the frequency range, where extracellular stimulation was highly effi- cacious, no responses could be generated using intracellular stimulation. A region in the amplitude-frequency stimulation space was identified where OFF-RGCs could be preferentially stimulated over ON-RGCs. We found that the inability of RGCs to respond at high frequencies of intracellular stimulation is likely the result of the axon acting as a low pass filter. Significance There is no direct translation of the results obtained with intracellular stimulation to those that employ extracellular stimulation.