Theoretical analysis of optogenetic spiking with ChRmine, bReaChES and CsChrimson-expressing neurons for retinal...

Objective.Optogenetics has emerged as a promising technique for neural prosthetics, especially retinal prostheses, with unprecedented spatiotemporal resolution. Newly discovered opsins with high light sensitivity and fast temporal kinetics can provide sufficient temporal resolution at safe light powers and overcome the limitations of presently used opsins. It is also important to formulate accurate mathematical models for optogenetic retinal prostheses, which can facilitate optimization of photostimulation factors to improve the performance.Approach.A detailed theoretical analysis of optogenetic excitation of model retinal ganglion neurons (RGNs) and hippocampal neurons expressed with already tested opsins for retinal prostheses, namely, ChR2, ReaChR and ChrimsonR, and also with recently discovered potent opsins CsChrimson, bReaChES and ChRmine, was carried out.Main results.Under continuous illumination, ChRmine-expressing RGNs begin to respond at very low irradiances ∼10^-4mW mm^-2, and evoke firing upto ∼280 Hz, highest among other opsin-expressing RGNs, at 10^-2mW mm^-2. Under pulsed illumination at randomized photon fluxes, ChRmine-expressing RGNs respond to changes in pulse to pulse irradiances upto four logs, although very bright pulses >10¹⁴photons mm^-2s^-1block firing in these neurons. The minimum irradiance threshold for ChRmine-expressing RGNs is lower by two orders of magnitude, whereas, the first spike latency in ChRmine-expressing RGNs is shorter by an order of magnitude, alongwith stable latency of subsequest spikes compared to others. Further, a good set of photostimulation parameters were determined to achieve high-frequency control with single spike resolution at minimal power. Although ChrimsonR enables spiking upto 100 Hz in RGNs, it requires very high irradiances. ChRmine provides control at light powers that are two orders of magnitude smaller than that required with experimentally studied opsins, while maintaining single spike temporal resolution upto 40 Hz.Significance.The present study highlights the importance of ChRmine as a potential opsin for optogenetic retinal prostheses.