Sub-second multi-channel magnetic control of select neural circuits in behaving flies

Abstract Precisely timed activation of genetically targeted cells is a powerful tool for studying neural circuits and controlling cell-based therapies. Magnetic control of cell activity or “magnetogenetics” using magnetic nanoparticle heating of temperature-sensitive ion channels enables remote, non-invasive activation of neurons for deep-tissue applications and studies of freely behaving animals. However, the in vivo response time of thermal magnetogenetics is currently tens of seconds, which prevents the precise temporal modulation of neural activity similar to light-based optogenetics. Moreover, magnetogenetics has not provided a means to selectively activate multiple channels to drive behavior. Here we demonstrate that by combining magnetic nanoparticles with a rate-sensitive thermoreceptor (TRPA1-A) it is possible to achieve sub-second behavioral responses in Drosophila melanogaster. Furthermore, by tuning the properties of magnetic nanoparticles to respond to different magnetic field strengths and frequencies, we can achieve fast, multi-channel stimulation, analogous to optogenetic stimulation with different wavelengths of light. These results bring magnetogenetics closer to the temporal resolution and multiplexed stimulation possible with optogenetics while maintaining the minimal invasiveness and deep-tissue stimulation only possible by magnetic control.

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Sub-second multi-channel magnetic control of select neural circuits in behaving flies

10.1101/2021.03.15.435264 ◽

2021 ◽

Author(s):

Charles Sebesta ◽

Daniel Torres ◽

Boshuo Wang ◽

Zhongxi Li ◽

Guillaume Duret ◽

...

Keyword(s):

Magnetic Nanoparticles ◽

Neural Circuits ◽

Cell Activity ◽

Temperature Sensitive ◽

Magnetic Control ◽

Deep Tissue ◽

Minimal Invasiveness ◽

Non Invasive ◽

Freely Behaving

Precisely timed activation of genetically targeted cells is a powerful tool for studying neural circuits and controlling cell-based therapies. Magnetic control of cell activity or "magnetogenetics" using magnetic nanoparticle heating of temperature-sensitive ion channels enables remote, non-invasive activation of neurons for deep-tissue applications and studies of freely behaving animals. However, the in vivo response time of thermal magnetogenetics is currently tens of seconds, which prevents the precise temporal modulation of neural activity similar to light-based optogenetics. Moreover, magnetogenetics has not provided a means to selectively activate multiple channels to drive behavior. Here we demonstrate that by combining magnetic nanoparticles with a rate-sensitive thermoreceptor (TRPA1-A) it is possible to achieve sub-second behavioral responses in Drosophila melanogaster. Furthermore, by tuning the properties of magnetic nanoparticles to respond to different magnetic field strengths and frequencies, we can achieve fast, multi-channel stimulation, analogous to optogenetic stimulation with different wavelengths of light. These results bring magnetogenetics closer to the temporal resolution and multiplexed stimulation possible with optogenetics while maintaining the minimal invasiveness and deep-tissue stimulation only possible by magnetic control.

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Large-Scale Chronically Implantable Precision Motorized Microdrive Array for Freely Behaving Animals

Journal of Neurophysiology ◽

10.1152/jn.90687.2008 ◽

2008 ◽

Vol 100 (4) ◽

pp. 2430-2440 ◽

Cited By ~ 40

Author(s):

Jun Yamamoto ◽

Matthew A. Wilson

Keyword(s):

Single Unit ◽

Large Scale ◽

Neural Circuits ◽

Brain Regions ◽

Unit Recording ◽

Chronic Recording ◽

Large Numbers ◽

Freely Behaving

Multiple single-unit recording has become one of the most powerful in vivo electro-physiological techniques for studying neural circuits. The demand has been increasing for small and lightweight chronic recording devices that allow fine adjustments to be made over large numbers of electrodes across multiple brain regions. To achieve this, we developed precision motorized microdrive arrays that use a novel motor multiplexing headstage to dramatically reduce wiring while preserving precision of the microdrive control. Versions of the microdrive array were chronically implanted on both rats (21 microdrives) and mice (7 microdrives), and relatively long-term recordings were taken.

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Highly sensitive room-temperature method of non-invasive in vivo detection of magnetic nanoparticles

Journal of Magnetism and Magnetic Materials ◽

10.1016/j.jmmm.2009.02.108 ◽

2009 ◽

Vol 321 (10) ◽

pp. 1658-1661 ◽

Cited By ~ 30

Author(s):

Maxim P. Nikitin ◽

Petr M. Vetoshko ◽

Nikolai A. Brusentsov ◽

Petr I. Nikitin

Keyword(s):

Magnetic Nanoparticles ◽

Room Temperature ◽

Non Invasive ◽

In Vivo Detection ◽

Temperature Method ◽

Highly Sensitive

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Neuronal networks in the spotlight

e-Neuroforum ◽

10.1007/s13295-013-0042-4 ◽

2013 ◽

Vol 19 (2) ◽

Author(s):

F. Helmchen ◽

M. Hübener

Keyword(s):

Neuronal Networks ◽

Neural Circuits ◽

Calcium Influx ◽

Fluorescent Proteins ◽

Activity Patterns ◽

Cell Activity ◽

Movement Control ◽

Dynamic Activity ◽

Two Photon Microscopy

AbstractThe brain’s astounding achievements regarding movement control and sensory processing are based on complex spatiotemporal activity patterns in the relevant neuronal networks. Our understanding of neuronal network activity is, however, still poor, not least because of the experimental difficulties in directly observing neural circuits at work in the living brain (in vivo). Over the last decade, new opportunities have emerged-especially utilizing two-photon microscopy-to investigate neuronal networks in action. Central to this progress was the development of fluorescent proteins that change their emission depending on cell activity, enabling the visualization of dynamic activity patterns in local neuronal populations. Currently, genetically encoded calcium indicators, proteins that indicate neuronal activity based on action potential-evoked calcium influx, are being increasingly used. Long-term expression of these indicators allows repeated monitoring of the same neurons over weeks and months, such that the stability and plasticity of their functional properties can be characterized. Furthermore, permanent indicator expression facilitates the correlation of cellular activity patterns and behavior in awake animals. Using examples from recent studies of information processing in the mouse neocortex, we review in this article these fascinating new possibilities and discuss the great potential of the fluorescent proteins to elucidate the mysteries of neural circuits.

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Optogenetic Manipulation of Olfactory Responses in Transgenic Zebrafish: A Neurobiological and Behavioral Study

International Journal of Molecular Sciences ◽

10.3390/ijms22137191 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7191

Author(s):

Yun-Mi Jeong ◽

Tae-Ik Choi ◽

Kyu-Seok Hwang ◽

Jeong-Soo Lee ◽

Robert Gerlai ◽

...

Keyword(s):

Olfactory System ◽

Neural Circuits ◽

Transgenic Fish ◽

Neural System ◽

Transgenic Zebrafish ◽

Olfactory Responses ◽

Non Invasive ◽

Zebrafish Larvae ◽

Calcium Indicator

Olfaction is an important neural system for survival and fundamental behaviors such as predator avoidance, food finding, memory formation, reproduction, and social communication. However, the neural circuits and pathways associated with the olfactory system in various behaviors are not fully understood. Recent advances in optogenetics, high-resolution in vivo imaging, and reconstructions of neuronal circuits have created new opportunities to understand such neural circuits. Here, we generated a transgenic zebrafish to manipulate olfactory signal optically, expressing the Channelrhodopsin (ChR2) under the control of the olfactory specific promoter, omp. We observed light-induced neuronal activity of olfactory system in the transgenic fish by examining c-fos expression, and a calcium indicator suggesting that blue light stimulation caused activation of olfactory neurons in a non-invasive manner. To examine whether the photo-activation of olfactory sensory neurons affect behavior of zebrafish larvae, we devised a behavioral choice paradigm and tested how zebrafish larvae choose between two conflicting sensory cues, an aversive odor or the naturally preferred phototaxis. We found that when the conflicting cues (the preferred light and aversive odor) were presented together simultaneously, zebrafish larvae swam away from the aversive odor. However, the transgenic fish with photo-activation were insensitive to the aversive odor and exhibited olfactory desensitization upon optical stimulation of ChR2. These results show that an aversive olfactory stimulus can override phototaxis, and that olfaction is important in decision making in zebrafish. This new transgenic model will be useful for the analysis of olfaction related behaviors and for the dissection of underlying neural circuits.

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In vivo assay of cortical microcircuitry in frontotemporal dementia: a platform for experimental medicine studies

10.1101/416388 ◽

2018 ◽

Cited By ~ 1

Author(s):

Alexander D Shaw ◽

Laura E Hughes ◽

Rosalyn Moran ◽

Ian Coyle-Gilchrist ◽

Tim Rittman ◽

...

Keyword(s):

Frontotemporal Dementia ◽

Neural Circuits ◽

Case Control ◽

Experimental Medicine ◽

Non Invasive ◽

Cortical Responses ◽

Sensory Predictions ◽

Local Coupling ◽

Laminar Specificity

AbstractThe analysis of neural circuits can provide critical insights into the mechanisms of neurodegeneration and dementias, and offer potential quantitative biological tools to assess novel therapeutics. Here we use behavioural variant frontotemporal dementia (bvFTD) as a model disease. We demonstrate that inversion of canonical microcircuit models to non-invasive human magnetoecphalography can identify the regional- and laminar-specificity of bvFTD pathophysiology, and their parameters can accurately differentiate patients from matched healthy controls. Using such models, we show that changes in local coupling in frontotemporal dementia underlie the failure to adequately establish sensory predictions, leading to altered prediction error responses in a cortical information-processing hierarchy. Using machine learning, this model-based approach provided greater case-control classification accuracy than conventional evoked cortical responses. We suggest that this approach provides an in vivo platform for testing mechanistic hypotheses about disease progression and pharmacotherapeutics.

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Direct focus sensing and shaping for high-resolution multi-photon imaging in deep tissue

10.1101/2021.08.04.455159 ◽

2021 ◽

Author(s):

Jianan Qu ◽

ZHONGYA QIN ◽

ZHENTAO SHE ◽

CONGPING CHEN ◽

WANJIE WU ◽

...

Keyword(s):

High Resolution ◽

Adaptive Optics ◽

High Sensitivity ◽

Deep Tissue ◽

Non Invasive ◽

Mouse Cortex ◽

Intact Brain ◽

Resolution Imaging

High-resolution optical imaging of deep tissue in-situ such as the living brain is fundamentally challenging because of the aberration and scattering of light. In this work, we develop an innovative adaptive optics three-photon microscope based on direct focus sensing and shaping that can accurately measure and effectively compensate for both low- and high-order specimen-induced aberrations and recover near-diffraction-limited performance at depth. A conjugate adaptive optics configuration with remote focusing enables in vivo imaging of fine neuronal structures in the mouse cortex through the intact skull up to a depth of 750 um below pia, making high-resolution microscopy in cortex near non-invasive. Functional calcium imaging with high sensitivity and accuracy, and high-precision laser-mediated microsurgery through the intact skull were demonstrated. Moreover, we also achieved in vivo high-resolution imaging of the deep cortex and subcortical hippocampus up to 1.1 mm below pia within the intact brain.

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