Direct measurement of bipolar cell responses to electrical stimulation in wholemount mouse retina

Objective. This in vitro investigation examines the response of retinal bipolar cells to extracellular electrical stimulation. Approach. In vitro investigations characterizing the response of retinal neurons to electrical stimulation have primarily focused on retinal ganglion cells because they are the output neurons of the retina and their superficial position in the retina makes them readily accessible to in vitro recording techniques. Thus, the majority of information regarding the response of inner retinal neurons has been inferred from ganglion cell activity. Here we use patch clamp electrophysiology to directly record electrically-evoked activity in bipolar cells within the inner retina of normal Tg(Gng13-EGFP)GI206Gsat and degenerate rd10 Tg(Gng13-EGFP)GI206Gsat mice using a wholemount preparation. Main results. Bipolar cells respond to electrical stimulation with time-locked depolarizing voltage transients. The latency of the response declines with increases in stimulation amplitude. A desensitizing response is observed during repeated stimulation with 25 ms biphasic current pulses delivered at pulse rates greater than 6 pps. A burst of long-latency (200-1000 ms) inhibitory postsynaptic potentials are evoked by the stimulus and the burst exhibits evidence of a lower and upper stimulation threshold. Significance. These results provide insights into the various types of bipolar cell activity elicited by electrical stimulation and may be useful for future retinal prosthesis stimulation protocols. This investigation uses patch clamp electrophysiology to provide direct analysis of ON-type bipolar cell responses to electrical stimulation in a wholemount retina preparation. It explores the effects of variable stimulus amplitudes, pulse widths, and frequencies in both normal and degenerate retina. The analysis adds to a body of work largely based upon indirect measurements of bipolar cell activity, and the methodology demonstrates an alternative retina preparation technique in which to acquire single-cell activity.