Theoretical Analysis of Low-power Bidirectional Optogenetic Control of High-frequency Neural Codes with Single Spike Resolution

Bansal, Himanshu; Gupta, Neha; Roy, Sukhdev

doi:10.1016/j.neuroscience.2020.09.022

Cited by 13 publications

(31 citation statements)

References 70 publications

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“…1h , Supplementary Fig. 1c ), as already previously shown 21 , 24 , whereas the blue-shift of λ rev for the ChRmine tandem with L4 (Fig. 1f, h ) is explained by the blue-shifted activation spectrum of ChRmine compared to Chrimson 25 and its presumably large single-channel conductance.…”

Section: Resultssupporting

confidence: 83%

BiPOLES is an optogenetic tool developed for bidirectional dual-color control of neurons

et al. 2021

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Optogenetic manipulation of neuronal activity through excitatory and inhibitory opsins has become an indispensable experimental strategy in neuroscience research. For many applications bidirectional control of neuronal activity allowing both excitation and inhibition of the same neurons in a single experiment is desired. This requires low spectral overlap between the excitatory and inhibitory opsin, matched photocurrent amplitudes and a fixed expression ratio. Moreover, independent activation of two distinct neuronal populations with different optogenetic actuators is still challenging due to blue-light sensitivity of all opsins. Here we report BiPOLES, an optogenetic tool for potent neuronal excitation and inhibition with light of two different wavelengths. BiPOLES enables sensitive, reliable dual-color neuronal spiking and silencing with single- or two-photon excitation, optical tuning of the membrane voltage, and independent optogenetic control of two neuronal populations using a second, blue-light sensitive opsin. The utility of BiPOLES is demonstrated in worms, flies, mice and ferrets.

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Section: Resultssupporting

confidence: 83%

BiPOLES is an optogenetic tool developed for bidirectional dual-color control of neurons

et al. 2021

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

2021

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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 ∼10−4 mW mm−2, and evoke firing upto ∼280 Hz, highest among other opsin-expressing RGNs, at 10−2 mW 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 >1014 photons mm−2 s−1 block 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.

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“…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].…”

Section: Discussionmentioning

confidence: 99%

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

Cruzado

Willats

et al. 2023

Preprint

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Recent advances in neurotechnology enable exciting new experiments, including novel paradigms such as closed-loop optogenetic control that achieve powerful causal interventions. At the same time, improved computational models are capable of reproducing behavior and neural activity with increasing fidelity. However, the complexities of these advances can make it difficult to reap the benefits of bridging model and experiment, such asin-silicoexperiment prototyping or direct comparison of model output to experimental data. We can bridge this gap more effectively by incorporating the simulation of the experimental interface into our models, but no existing tool integrates optogenetics, electrode recording, and flexible closed-loop processing with neural population simulations. To address this need, we have developed the Closed-Loop, Electrophysiology, and Optogenetics experiment simulation testbed (Cleo). Cleo is a Python package built on the Brian 2 simulator enabling injection of recording and stimulation devices as well as closed-loop control with realistic latency into a spiking neural network model. Here we describe the design, features, and use of Cleo, including validation of the individual system components. We further demonstrate its utility in three case studies using a variety of existing models and discuss potential applications for advancing causal neuroscience.

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Theoretical Analysis of Low-power Bidirectional Optogenetic Control of High-frequency Neural Codes with Single Spike Resolution

Cited by 13 publications

References 70 publications

BiPOLES is an optogenetic tool developed for bidirectional dual-color control of neurons

BiPOLES is an optogenetic tool developed for bidirectional dual-color control of neurons

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

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

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