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, opsinexpression 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.

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

“…Initial efforts in the area include accurate modeling of ChR2 photocycle with three, four and six-state models (Nikolic et al 2009, Grossman et al 2013, exploration of light to spike process under continuous and pulsed illumination (Grossman et al 2011), illumination of sub-cellular compartments (Grossman et al 2013), analysis of the sensitivity of activation threshold to tissue medium (scattering and absorption) and illumination devices (Foutz et al 2012, Arlow et al 2013. Theoretical modeling of optogenetic inhibition was also reported with light-driven chloride pumps and channels (Bansal et al 2020a(Bansal et al , 2020b. Detailed theoretical analysis of newly discovered opsins such as ultrafast Chronos and vf-Chrimson provided better understanding of their kinetics in different types of neurons (Saran et al 2018, Gupta et al 2019.…”

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].…”

Neural pathways from hypothalamic orexin neurons to the ventrolateral preoptic area mediate sleep impairments induced by conditioned fear

“…One possibility is that the wide orexinergic projections in the other brain regions, such as the cortex ( Li et al, 2010 ), the locus coeruleus and dorsal raphe nucleus ( Peyron et al, 1998 ; Mieda et al, 2011 ), and the paraventricular thalamus ( Ren et al, 2018 ), give off a compensatory effect on wake or arousal when the orexinergic terminals in the VLPO were inhibited, but this needs additional experimental evidence. Another possibility is that NpHR3.0-mCherry is less efficient when it acts on presynaptic terminals ( Bansal et al, 2020 ), therefore, more effective inhibition experiments are needed.…”