Comparison of low-power, high-frequency and temporally precise optogenetic inhibition of spiking in NpHR, eNpHR3.0 and Jaws-expressing neurons

Abstract

A detailed theoretical analysis of low-power, high-frequency and temporally precise optogenetic inhibition of neuronal spiking, with red-shifted opsins namely, NpHR, eNpHR3.0 and Jaws, has been presented. An accurate model for inhibition of spiking in these opsins expressed hippocampal neurons that includes the important rebound activity of chloride ions across the membrane has been formulated. The effect of various parameters including irradiance, pulse width, frequency, opsin-expression density and chloride concentration has been studied in detail. Theoretical simulations are in very good agreement with reported experimental results. The chloride concentration gradient directly affects the photocurrent and inhibition capacity in all three variants. eNpHR3.0 shows smallest inhibitory post-synaptic potential plateau at higher frequencies. The time delay between light stimulus and target spike is crucial to minimize irradiance and expression density thresholds for suppressing individual spike. Good practical values of photostimulation parameters have been obtained empirically for peak photocurrent, time delay and 100% spiking inhibition, at continuous and pulsed illumination. Under continuous illumination, complete inhibition of neural activity in Jaws-expressing neurons takes place at minimum irradiance of 0.2 mW mm−2 and expression density of 0.2 mS cm−2, whereas for pulsed stimulation, it is at minimum irradiance of 0.6 mW mm−2 and 5 ms pulse width, at 10 Hz. It is shown that Jaws and eNpHR3.0 are able to invoke single spike precise inhibition up to 160 and 200 Hz, respectively. The study is useful in designing new experiments, understanding temporal spike coding and bidirectional control, and curing neurological disorders.