Timing is Everything: Stochastic Optogenetic Stimulation Reduces Adaptation in Retinal Ganglion Cells

Optogenetics gives us unprecedented power to investigate brain connectivity. The ability to activate neural circuits with single cell resolution and its ease of application has provided a wealth of knowledge in brain function. More recently, optogenetics has shown tremendous utility in prosthetics applications, including vision restoration for patients with retinitis pigmentosa. One of the disadvantages of optogenetics, however, is its poor temporal bandwidth, i.e. the cell’s inability to fire at a rate that matches the optical stimulation rate at high frequencies (>30 Hz). This research proposes a new strategy to overcome the temporal limits of optogenetic stimulation. Using whole-cell current clamp recordings in mouse retinal ganglion cells expressing channelrhodopsin-2 (H134R variant), we observed that randomizing inter-pulse intervals can significantly increase a retinal ganglion cell’s temporal response to high frequency stimulation.Clinical Relevance— A significant disadvantage of optogenetic stimulation is its poor temporal dynamics which prohibit its widespread use in retinal prosthetics. We have shown that randomizing the interval between stimulation pulses reduces adaptation in retinal ganglion cells. This stimulation strategy may contribute to new levels of functional restoration in therapeutics which incorporate optogenetics.