Abstract
Purpose :
In the investigation of the electrically-elicited color perception in the blind Argus II patients, we found that increase of the stimulation frequency led to not only blue-shifted color percepts but also elongated shapes of the phosphene sensation in some patients. Here we studied the spatial characteristics of the retinal activation under frequency modulation (FM), seeking to decode the changes in the phosphene shape observed clinically.
Methods :
We used Ca2+ imaging to visualize spatial responses in wholemount mouse retina (wildtype C57BL/6 mice). AAV2-CAG-GCaMP6f was used to impart Ca2+-dependent fluorescence on mouse retinal ganglion cells (RGCs). The retina was acutely dissected 3-4 weeks after intravitreal injection of the viral vectors and the wholemount was placed in an electrode array embedded chamber for simultaneous electrical stimulation and optical recording. Biphasic stimuli of 1-ms pulse width were delivered repetitively for 1-s at the frequency ranging between 5 and 120 Hz, similar to those tested in humans. A cocktail of synaptic blockers was applied to pharmacologically isolate the ganglion cell. Changes in the fluorescence (ΔF/F) of the pixels in the cells were analyzed.
Results :
The resulting ΔF/F maps show that increased stimulation frequency led to marked enhancement in the RGC activation in the direction along the axons of passage opposite to the optic disc. In comparison, increased amplitude resulted in a uniform expansion of a focal activation in all directions. Increasing the stimulation frequency from 5 Hz to 120 Hz reduced the standard deviation of the activation angle (Δθ) by an average of 60%, whereas increasing the stimulation amplitude while keeping a 5Hz stimulation rate did not result in a significant change in Δθ. When the synaptic input to the RGCs was blocked, the directional activation resulting from FM was largely maintained whereas the focal activation resulting from amplitude modulation (AM) was substantially eliminated.
Conclusions :
Increased stimulation frequency resulted in increasingly directional activation map of the RGCs, consistent with the elongated phosphene sensation reported by some Argus II patients. The insensitivity of the directional activation to synaptic blockers and the alignment between the activation direction and the axon orientation strongly suggest an antidromic mechanism that may involve enhanced activation by axonal multi-pulse integration.
This is a 2021 ARVO Annual Meeting abstract.