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

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: July 26, 2021

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

Language: Английский

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Theoretical analysis of low-power deep synergistic sono-optogenetic excitation of neurons by co-expressing light-sensitive and mechano-sensitive ion-channels

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 6, 2025

The present challenge in neuroscience is to non-invasively exercise low-power and high-fidelity control of neurons situated deep inside the brain. Although, two-photon optogenetic excitation can activate millimeter depth with sub-cellular specificity millisecond temporal resolution, it also cause heating targeted tissue. On other hand, sonogenetics modulate cellular activity expressed mechano-sensitive proteins deeper areas brain less spatial selectivity. We a theoretical analysis synergistic sono-optogenetic method overcome these limitations by co-expressing (MscL-I92L) ion-channel light-sensitive (CoChR/ChroME2s/ChRmine) hippocampal neurons. It shown that presence low-amplitude subthreshold ultrasound pulses, threshold for neural spiking reduces drastically 73% MscL-I92L-CoChR (0.021 mW/µm2), 66% MscL-I92L-ChroME2s (0.029 64% MscL-I92L-ChRmine (0.013 mW/µm2) at 5 Hz. allows up 1.2 cm combination. useful design new experiments multimodal neuroprosthetic devices circuits.

Language: Английский

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Theoretical prediction of broadband ambient light optogenetic vision restoration with ChRmine and its mutants

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: May 21, 2024

Vision restoration is one of the most promising applications optogenetics. However, it limited due to poor-sensitivity, slow-kinetics and narrow band absorption spectra opsins. Here, a detailed theoretical study retinal ganglion neurons (RGNs) expressed with ChRmine, ReaChR, CoChR, CatCh their mutants, near monochromatic LEDs, broadband sunlight, halogen lamp, RGB LED light, pure white light sources has been presented. All opsins exhibit improved sensitivity larger photocurrent on illuminating compared LEDs. ChRmine allows firing at ambient sunlight (1.5 nW/mm2) (1.2 nW/mm2), which lowest among considered. The activation spectrum its mutants also useful restore color sensitivity. Although exhibits slower turn-off kinetics high-fidelity spikes can be evoked upto 50 Hz. This limit extends 80 Hz hsChRmine mutant although requires double irradiance ChRmine. present shows that allow RGNs for goggle-free optogenetic prostheses quality restored vision.

Language: Английский

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Theoretical analysis of low power optogenetic control of synaptic plasticity with subcellular expression of CapChR2 at postsynaptic spine

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 1, 2025

Precise control of intracellular calcium ([Formula: see text]) concentration at the synaptic neuron terminal can unravel mechanism behind computation, learning, and memory formation inside brain. Recently, discovery [Formula: text]-permeable channelrhodopsins (CapChRs) has opened opportunity to effectively text] using optogenetics. Here, we present a new theoretical model for precise optogenetic with newly discovered CapChR2 postsynaptic neuron. A detailed analysis coincident stimulation presynaptic terminal, spine activation CapChR2-expressing shows different ways concentration. Irradiance-dependent flow is an additional advantage this novel method. The minimum threshold light irradiance optimal ranges time lag among stimulations frequencies have also been determined. It shown that efficacy occurs 20 µW/mm2 electrical CapChR2-expressed spine. provides means direct text]-based plasticity, better understanding learning processes, opens prospects targeted therapeutic interventions modulate function address various neurological disorders.

Language: Английский

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

Journal of Neural Engineering, Journal Year: 2021, Volume and Issue: 18(4), P. 0460b8 - 0460b8

Published: July 6, 2021

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

Language: Английский

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Ultra‐low power deep sustained optogenetic excitation of human ventricular cardiomyocytes with red‐shifted opsins: a computational study

The Journal of Physiology, Journal Year: 2022, Volume and Issue: 600(21), P. 4653 - 4676

Published: Sept. 7, 2022

Abstract The main challenge in cardiac optogenetics is to have low‐power, high‐fidelity deep excitation of cells with minimal invasiveness and heating. We present a detailed computational study optogenetic human ventricular cardiomyocytes (HVCMs) new ChRmine, bReaChES CsChrimson red‐shifted opsins overcome the challenge. Action potentials (APs) ChRmine‐expressing HVCMs can be triggered at 6 µW mm −2 (10 ms pulse) 0.7 (100 585 nm, which two orders magnitude lower than ChR2(H134R). This enables safe sustained deeply situated ChRmine (7.46 mm) (6.21 light source pericardium surface. Deeper up 10.2 achieved by illuminating 650 nm. Photostimulation conditions for minimum charge transfer during APs been determined, important tissue health under excitation. AP duration all constant 100 pulse width but increases thereafter. Interestingly, frequency irradiance continuous illumination, are suppressed higher irradiances. optimal range each opsin excite has determined. Under photostimulation conditions, precisely 2.5 Hz, while latency power sequence remain most stable an order lower, respectively, HVCMs. highlights importance resynchronization, termination tachycardia designing pacemakers enhanced battery life. image Key points work formulation accurate theoretical models control expressed newly discovered (ChRmine, CsChrimson). action opsin‐expressing only evoked certain ultra‐low (6 10 or nm), three reported results. Ongoing illumination nm 2 . due its faster recovery from desensitized state. Optogenetic possible ∼7.46 on outer surface respectively. opens prospects energy‐efficient light‐induced pacemakers, resynchronization tachycardia.

Language: Английский

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Co-expressing fast channelrhodopsin with step-function opsin overcomes spike failure due to photocurrent desensitization in optogenetics: a theoretical study

Journal of Neural Engineering, Journal Year: 2022, Volume and Issue: 19(2), P. 026032 - 026032

Published: March 23, 2022

Objective.A fundamental challenge in optogenetics is to elicit long-term high-fidelity neuronal spiking with negligible heating. Fast channelrhodopsins (ChRs) require higher irradiances and cause spike failure due photocurrent desensitization under sustained illumination, whereas, more light-sensitive step-function opsins (SFOs) exhibit prolonged depolarization insufficient fast response for spiking.Approach.We present a novel method overcome this limitation by co-expressing ChRs SFOs. A detailed theoretical analysis of ChETA co-expressed different SFOs, namely ChR2(C128A), ChR2(C128S), stabilized opsin (SSFO) ultra-high light sensitivity (SOUL), expressing hippocampal neurons has been carried out formulating their accurate models.Main results.ChETA-SFO-expressing shows stable that overcomes failure. Spiking fidelity these can be even at lower subsequent pulses (77% initial pulse intensity ChETA-ChR2(C128A)-expressing neurons) or using red-shifted appropriate intervals. High-fidelity upto 60 Hz evoked ChETA-ChR2(C128S), ChETA-SSFO ChETA-SOUL-expressing neurons, which cannot attained only SFOs.Significance.The study provides important insights about photostimulation protocols bi-stable switching neurons. This new approach means low-power, high-frequency optogenetic necessary various neural functions neurodegenerative disorders, enhance the utility biomedical applications.

Language: Английский

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Optogenetic Generation of Neural Firing Patterns with Temporal Shaping of Light Pulses

Photonics, Journal Year: 2023, Volume and Issue: 10(5), P. 571 - 571

Published: May 13, 2023

The fundamental process of information processing and memory formation in the brain is associated with complex neuron firing patterns, which can occur spontaneously or be triggered by sensory inputs. Optogenetics has revolutionized neuroscience enabling precise manipulation neuronal activity patterns specified neural populations using light. However, light pulses used optogenetics have been primarily restricted to square waveforms. Here, we present a detailed theoretical analysis temporal shaping optogenetic excitation hippocampal neurons neocortical fast-spiking interneurons expressed ultrafast (Chronos), fast (ChR2), slow (ChRmine) channelrhodopsins. Optogenetic studied different shapes that include square, forward-/backward ramps, triangular, left-/right-triangular, Gaussian, left-/right-Gaussian, positive-sinusoidal, left-/right-positive sinusoidal. Different result significantly photocurrent amplitudes kinetics, spike-timing, spontaneous rate. For short duration stimulations, left-Gaussian pulse results larger ChR2 Chronos than same energy density. Time peak each opsin minimum at right-Gaussian pulse. optimal width achieve for non-square 10 ms Chronos, 50 ChRmine. evoke spike minimized on choosing Gaussian ChR2, positive-sinusoidal demonstrate waveforms generate more naturalistic spiking compared traditional pulses. These findings provide valuable insights development new strategies better simulate manipulate brain, potential improve our understanding cognitive processes treatment neurological disorders.

Language: Английский

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Optogenetically mediated large volume suppression and synchronized excitation of human ventricular cardiomyocytes

Pflügers Archiv - European Journal of Physiology, Journal Year: 2023, Volume and Issue: 475(12), P. 1479 - 1503

Published: July 7, 2023

Language: Английский

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

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 28, 2023

Abstract Systems neuroscience has experienced an explosion of new tools for reading and writing neural activity, enabling exciting experiments such as all-optical or closed-loop control that effect powerful causal interventions. At the same time, improved computational models are capable reproducing behavior activity with increasing fidelity. Unfortunately, these advances have drastically increased complexity integrating different lines research, resulting in missed opportunities untapped potential suboptimal experiments. Experiment simulation can help bridge this gap, allowing model experiment to better inform each other by providing a low-cost testbed design, validation, methods engineering. Specifically, be achieved incorporating experimental interface into our models, but no existing tool integrates optogenetics, two-photon calcium imaging, electrode recording, flexible processing population simulations. To address need, we developed Cleo: Closed-Loop, Electrophysiology, Optophysiology testbed. Cleo is Python package injection recording stimulation devices well realistic latency Brian spiking network model. It only publicly available currently supporting multi-opsin/wavelength optogenetics. facilitate adoption extension community, open-source, modular, tested, documented, export results various data formats. Here describe design features Cleo, validate output individual components integrated experiments, demonstrate its utility advancing optogenetic techniques prospective using previously published systems models.

Language: Английский

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