Theoretical optimization of high-frequency optogenetic spiking of red-shifted very fast-Chrimson-expressing neurons

Abstract

A detailed theoretical analysis and optimization of high-fidelity, high-frequency firing of the red-shifted very-fast-Chrimson (vf-Chrimson) expressing neurons is presented. A four-state model for vf-Chrimson photocycle has been formulated and incorporated in Hodgkin-Huxley and Wang-Buzsaki spiking neuron circuit models. The effect of various parameters that include irradiance, pulse width, frequency, expression level, and membrane capacitance has been studied in detail. Theoretical simulations are in excellent agreement with recently reported experimental results. The analysis and optimization bring out additional interesting features. A minimal pulse width of 1.7 ms at 23 mW∕mm 2 induces a peak photocurrent of 1250 pA. Optimal irradiance (0.1 mW∕mm 2) and pulse width (50 μs) to trigger action potential have been determined. At frequencies beyond 200 Hz, higher values of expression level and irradiance result in spike failure. Singlet and doublet spiking fidelity can be maintained up to 400 and 150 Hz, respectively. The combination of expression level and membrane capacitance is a crucial factor to achieve high-frequency firing above 500 Hz. Its optimization enables 100% spike probability of up to 1 kHz. The study is useful in designing new high-frequency optogenetic neural spiking experiments with desired spatiotemporal resolution, by providing insights into the temporal spike coding, plasticity, and curing neurodegenerative diseases.

Bridging model and experiment in systems neuroscience with Cleo: the Closed-Loop, Electrophysiology, and Optophysiology simulation testbed

“…Finally, users wanting to take advantage of state-of-the-art optogenetic innovations such as improved channel rhodopsins [145, 146, 147, 148, 149, 3, 150], chloride pumps [151, 152, 153] and channels [154, 155], and other innovative opsins [153, 4] will need to provide additional light and opsin model parameters. Thankfully, parameters for many such opsins are available in published literature [156, 157, 158, 159, 160].…”

Red Light Optogenetics in Neuroscience

“…Besides the advances in transfection and illumination, various other methods have facilitated the use of red light in optogenetics. Data-driven approaches and simulations are just one example: red-shifted opsins have been found through machine learning-based data mining, and the photocycle of Chrimson has been theoretically optimized through a mathematical model ( Gupta et al, 2019 ; Inoue et al, 2021 ). Similarly, local illumination enhancement through aluminum nanostructures has been simulated for the possible future use of lower overall illumination intensities ( Keck et al, 2021 ).…”

Principles of Optogenetic Methods and Their Application to Cardiac Experimental Systems

“…The first of these red-shifted variants to be discovered, VChR1 is maximally activated by green light (~530 nm), but retains strong photocurrents in amber light (590 nm), a wavelength that produced no measurable depolarization in ChR2-expressing cells. Further engineering of opsin chimeras and targeted mutant variants has led to an array of red-shifted opsins with large photocurrents and fast off-kinetics [C1V1 variants, red-activatable ChR (ReaChR), Chrimson] (Yizhar et al, 2011b; Lin et al, 2013; Klapoetke et al, 2014; Gupta et al, 2019). Several blue-shifted rhodopsin variants have also been identified.…”