Implantable devices for optogenetic studies and stimulation of excitable tissue

Matveev, M. V.; Ерофеев, А. И.; Terekhin, S. G.; Plotnikova, P. V.; Vorobyov, Konstantin V.; Власова, О. Л.

doi:10.1016/j.spjpm.2015.12.004

Cited by 6 publications

(3 citation statements)

References 12 publications

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“…Since MeOp showed unprecedented promiscuity for both Gq and Gi/o pathways by mutating its intracellular loops, we previously engineered a Gq-selective MeOp variant 25 , allowing for Gq-exclusive, red-light-resisting hybrid MeOp engineering in the future. Availability of these opsin mutants, together with the use of implanted optrodes 71,72 or two-photon excitation methods 73,74 , will enable optical control of the Gq pathway that influences vital physiological functions, such as Gq-induced blood pressure elevation and associated cardiac hypertrophy 75 , PI3K-induced neural plaque accumulation and inflammation in neurodegenerative diseases caused by the activation of downstream GSK3-beta and IKK a/b pathways 76 .…”

Section: Discussionmentioning

confidence: 99%

Engineered blue-shifted melanopsins for subcellular optogenetics

Wijayaratna,

Sacchetta,

Pedraza Gonzalez

et al. 2023

Preprint

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Melanopsin (MeOp) is a G protein-coupled Receptor (GPCR) family photopigment, expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs) that display remarkable functional diversity. In addition to non-image-forming visual functions, MeOp also controls signaling underlying the retina development, circadian clock, mood, and behavior. MeOp is bistable, recycles retinal, and can function under low retinaldehyde availability. It also activates multiple G protein heterotrimers. Though MeOp could be a versatile optogenetic tool, its potential, especially its utility for subcellular signaling control, is hampered by the broader spectral sensitivity spanning the entire visible range. Here, we use a recently reportedin silicotechnology called Automatic Rhodopsin Modeling (ARM) to identify blue-shifting mutations of MeOp and, ultimately, allow for imaging biosensors with red light without activating the opsin. Accordingly, ARM was used to construct validated quantum mechanics/molecular mechanics (QM/MM) models for mouse MeOp (mMeOp) to search and optimize a set of mutants featuring a blue-shifted light absorption. We demonstrate that four mutants of such can be successfully expressed and display the required resistance to activation by red light; however, they are activated by yellow, green, and blue light. Localized subcellular optical activation of these mutants in macrophage cells showed localized PIP3 generation and cell migration. Further characterization showed that MeOp blue-shifted mutants are also bistable. Altogether, our data demonstrate the computer-aided engineering feasibility of opsins with desired spectral properties for subcellular optogenetic applications.

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Section: Discussionmentioning

confidence: 99%

Engineered blue-shifted melanopsins for subcellular optogenetics

Wijayaratna,

Sacchetta,

Pedraza Gonzalez

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…Additionally, using MEAs for cell cultures does not violate the integrity of the cell membrane in comparison with the patch clamp (whole-cell). In experiments in vivo, MEAs make it possible to register neural activity in the target areas of the brain during the animal behavior and detect changes in neural correlations [12][13][14]. For this, a microelectrode array is implanted into the animal's brain, in accordance with the stereotaxic atlas.…”

Section: Introductionmentioning

confidence: 99%

An Open-Source Wireless Electrophysiological Complex for In Vivo Recording Neuronal Activity in the Rodent’s Brain

Ерофеев

Kazakov

Makarevich

et al. 2021

Sensors

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Multi-electrode arrays (MEAs) are a widely used tool for recording neuronal activity both in vitro/ex vivo and in vivo experiments. In the last decade, researchers have increasingly used MEAs on rodents in vivo. To increase the availability and usability of MEAs, we have created an open-source wireless electrophysiological complex. The complex is scalable, recording the activity of neurons in the brain of rodents during their behavior. Schematic diagrams and a list of necessary components for the fabrication of a wireless electrophysiological complex, consisting of a base charging station and wireless wearable modules, are presented.

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“…However, this approach requires direct optical access to brain tissue, which is difficult because blue light does not readily penetrate whole organisms; light must be delivered using costly specialized equipment such as custom blue light sources with fibre optics or two-photon illumination systems 6 . Additionally, given the need for invasive equipment implantation and sufficient power 7 , it is difficult to apply optogenetics for disease treatment in real clinical practice.…”

mentioning

confidence: 99%

A non-invasive, fast on/off “Odourgenetic” Method to Manipulate Physiology

et al. 2022

Preprint

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Manipulating molecular processes governing physiological functions has significant potential for clinical therapeutics and is an important approach to elucidate the cellular basis of physiological functions. Here, we designed a Odourgenetic system co-expressed Drosophila odorant receptor system (DORs) consisting of OR35a and OR83b, which were exclusively activated by their odor ligand, 2-pentanone. Applying 2-pentanone to DOR-expressing cells or tissues induced calcium influx and membrane depolarization. By inhalation of 2-pentanone, we successfully applied DORs to manipulate behaviour, control insulin secretion and regulate blood glucose and manipulate muscle contraction and associated limb movement. Because 2-pentanone rapidly enters the blood upon inhalation and leaves the body by exhalation, this odorant can be used with DORs to manipulate cellular function, and the manipulation can be terminated at any time. Such feature approach significantly improves the safety and controllability of DORs used in the clinic. Thus, the present study developed a non-invasive, controllable, fast on/off method to manipulate cellular activity and behaviour on a time scale of minutes.

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Implantable devices for optogenetic studies and stimulation of excitable tissue

Cited by 6 publications

References 12 publications

Engineered blue-shifted melanopsins for subcellular optogenetics

Engineered blue-shifted melanopsins for subcellular optogenetics

An Open-Source Wireless Electrophysiological Complex for In Vivo Recording Neuronal Activity in the Rodent’s Brain

A non-invasive, fast on/off “Odourgenetic” Method to Manipulate Physiology

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