Optogenetic Tractography for anatomo-functional characterization of cortico-subcortical neural circuits in non-human primates

Senova, Suhan; Poupon, Cyril; Dauguet, Julien; Stewart, Harry E.; Dugué, Guillaume P.; Jan, C; Hosomi, Koichi; Ralph, G; Barnes, L; Drouot, Xavier; Pouzat, Christophe; Mangin, Jean‐François; Pain, Frédéric; Doignon, Isabelle; Aron-Badin, Romina; Brouillet, Emmanuel; Boyden, Ed; Mitrophanous, Kyriacos; Hantraye, Philippe; Palfi, Stéphane

doi:10.1038/s41598-018-21486-8

Cited by 13 publications

(7 citation statements)

References 74 publications

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“…3T and using whole-body MR features such as parallel imaging further enforcing the usefulness of NHPs for translational research (Li and Zhang, 2017). In addition, NHP models can be used effectively to investigate neural circuitry with cutting-edge technologies such as optogenetics (Senova et al, 2018), which that can be coupled with MRI techniques to identify specific anatomical targets for further stimulation therapy.…”

Section: Rodents and Humansmentioning

confidence: 99%

Imaging and spectroscopic methods to investigate adult neurogenesis in vivo: New models and new avenues

2022

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Adult neurogenesis (AN) can be defined as the birth and development of new neurons in adulthood. Until the 1990s, AN was deemed not to happen after birth. Gradually, several groups demonstrated that specific zones of the brain of various species had a neurogenic potential. AN could be the key to treating a large range of neurodegenerative, neuropsychiatric, and metabolic diseases, with a better understanding of the mechanisms allowing for regeneration of new neurons. Despite this promising prospect, the existence of AN has not been validated in vivo in humans and therefore remains controversial. Moreover, the weight of AN-induced plasticity against other mechanisms of brain plasticity is not known, adding to the controversy. In this review, we would like to show that recent technical advances in brain MR imaging methods combined with improved models can resolve the debate.

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Section: Rodents and Humansmentioning

confidence: 99%

Imaging and spectroscopic methods to investigate adult neurogenesis in vivo: New models and new avenues

2022

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“…In this work, we focus on another significant issue, which is the ability to deliver enough fluence to large brain volumes down to several millimeters beneath the brain surface in order to activate the opsins with minimal mechanical invasiveness and thermal increases. Such requirements are essential if noninvasive optical modulation of large cortical volumes connected to deep brain nuclei is to be investigated in NHP models of central nervous dis orders, as recently proposed in a translational perspective [9,16]. The quantitation of the non-invasive optical stimulation of large volume of cortical tissues is also of great interest for the field of photobiomodulation (PBM).…”

Section: Introductionmentioning

confidence: 99%

Optical and thermal simulations for the design of optodes for minimally invasive optogenetics stimulation or photomodulation of deep and large cortical areas in non-human primate brain

et al. 2018

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The use of optogenetics or photobiomodulation in non-human primate (NHP) requires the ability to noninvasively stimulate large and deep cortical brain tissues volumes. In this context, the optical and geometrical parameters of optodes are critical. Methods and general guidelines to optimize these parameters have to be defined. Objective. We propose the design of an optode for safe and efficient optical stimulation of a large volume of NHP cortex, down to 3-5 mm depths without inserting fibers into the cortex. Approach. Monte Carlo simulations of optical and thermal transport have been carried out using the Geant4 application for tomographic emission (GATE) platform. Parameters such as the fiber diameter, numerical aperture, number of fibers and their geometrical arrangement have been studied. Optimal hardware parameters are proposed to obtain homogeneous fluence above the fluence threshold for opsin activation without detrimental thermal effects. Main results. The simulations show that a large fiber diameter and a large numerical aperture are preferable since they allow limiting power concentration and hence the resulting thermal increases at the brain surface. To obtain a volume of 200-500 mm 3 of brain tissues receiving a fluence above the opsin activation threshold for optogenetics or below a phototocixity threshold for photobiomodulation, a 4 fibers configuration is proposed. The optimal distance between the fibers was found to be 4 mm. A practical implementation of the optode has been performed and the corresponding fluence and thermal maps have been simulated. Significance. The Journal of Neural EngineeringOptical and thermal simulations for the design of optodes for minimally invasive optogenetics stimulation or photomodulation of deep and large cortical areas in non-human primate brainOriginal content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI. 6 Both authors contributed equally.1741-2552/18/065004+12$33.00 https://doi.org/10.1088/1741-2552/aadf97 J. Neural Eng. 15 (2018) 065004 (12pp) A Dubois et al 2 present study defines a method to optimize the design of optode and the choice of stimulation parameters for optogenetics and more generally light delivery to deep and large volumes of tissues in NHP brain with a controlled irradiance dosimetry. The general guidelines are the use of silica fibers with a large numerical aperture and a large diameter. The combination of several fibers is required if large volumes need to be stimulated while avoiding thermal effects.

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“…Senova and coworkers 93 studied the spatial distribution of light and its effects in large brain volumes of animal models. This study demonstrates that deep light penetration in the brain cortex is possible without detrimental photo and thermal damage to the organ.…”

Section: Challenges Of Current Optogenetic Strategies and Potential S...mentioning

confidence: 99%

The clinical potential of optogenetic interrogation of pathogenesis

Gao

Mehta

et al. 2023

Clinical & Translational Med

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Background Opsin‐based optogenetics has emerged as a powerful biomedical tool using light to control protein conformation. Such capacity has been initially demonstrated to control ion flow across the cell membrane, enabling precise control of action potential in excitable cells such as neurons or muscle cells. Further advancement in optogenetics incorporates a greater variety of photoactivatable proteins and results in flexible control of biological processes, such as gene expression and signal transduction, with commonly employed light sources such as LEDs or lasers in optical microscopy. Blessed by the precise genetic targeting specificity and superior spatiotemporal resolution, optogenetics offers new biological insights into physiological and pathological mechanisms underlying health and diseases. Recently, its clinical potential has started to be capitalized, particularly for blindness treatment, due to the convenient light delivery into the eye. Aims and methods This work summarizes the progress of current clinical trials and provides a brief overview of basic structures and photophysics of commonly used photoactivable proteins. We highlight recent achievements such as optogenetic control of the chimeric antigen receptor, CRISPR‐Cas system, gene expression, and organelle dynamics. We discuss conceptual innovation and technical challenges faced by current optogenetic research. Conclusion In doing so, we provide a framework that showcases ever‐growing applications of optogenetics in biomedical research and may inform novel precise medicine strategies based on this enabling technology.

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Optogenetic Tractography for anatomo-functional characterization of cortico-subcortical neural circuits in non-human primates

Cited by 13 publications

References 74 publications

Imaging and spectroscopic methods to investigate adult neurogenesis in vivo: New models and new avenues

Imaging and spectroscopic methods to investigate adult neurogenesis in vivo: New models and new avenues

Optical and thermal simulations for the design of optodes for minimally invasive optogenetics stimulation or photomodulation of deep and large cortical areas in non-human primate brain

The clinical potential of optogenetic interrogation of pathogenesis

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