Precisely timed activation of genetically targeted cells is a powerful tool for the study of neural circuits and control of 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 freely behaving animal studies. However, the in vivo response time of thermal magnetogenetics is currently tens of seconds, which prevents precise temporal modulation of neural activity. Moreover, magnetogenetics has yet to achieve in vivo multiplexed stimulation of different groups of neurons. Here we produce subsecond behavioural responses in Drosophila melanogaster by combining magnetic nanoparticles with a rate-sensitive thermoreceptor (TRPA1-A). Furthermore, by tuning magnetic nanoparticles to respond to different magnetic field strengths and frequencies, we achieve subsecond, multichannel stimulation. These results bring magnetogenetics closer to the temporal resolution and multiplexed stimulation possible with optogenetics while maintaining the minimal invasiveness and deep-tissue stimulation possible only by magnetic control.
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The main data supporting the results of this study are available within the paper and its Supplementary information. The raw videos generated for the study are too large for public sharing, but are available for research purposes from the corresponding authors upon reasonable request.
FlyTracker (Perona Lab, CalTech, v.1.0.5) was used to track the wing angle and position of flies within their respective chambers, and is publicly available online (https://www.vision.caltech.edu/datasets/). DeepLabCut (Mathis Lab, v.2.2.b9) was used to track fly wing angle and position for videos with shadows, and is publicly available online (http://www.mackenziemathislab.org/deeplabcut). Microsoft excel (v.16.54) was used for simple SLP and selectivity calculations. FLIR research studio (v.2.0) was used for thermal imaging.
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This research was developed with funding from the Defense Advanced Research Projects Agency of the United States of America (contract no. N66001-19-C-4020, received by J.T.R.). The views, opinions and/or findings expressed are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the US Government. This work was funded in part by the National Science Foundation: Neuronex innovation award no. 1707562 and grant no. C-1963 from the Welch Foundation received by J.T.R., as well as by the National Institutes of Health under award no. RO1MH107474 received by H.A.D. We thank J. Moon and P. Anikeeva (MIT) for useful discussions and guidance with magnetic multiplexing, sharing their design for the ac magnetometer and advising us on its operation.
The authors declare the following competing interests. S.M.G. has received research funding from Magstim. A.V.P. has received research funding, travel support, patent royalties, consulting fees, equipment loans, hardware donations and/or patent application support from Rogue Research, Tal Medical/Neurex, Magstim, MagVenture, Neuronetics, BTL Industries and Advise Connect Inspire. The remaining authors declare no competing interests.
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Supplementary Figs. 1–12 and video legends.
Slow thermal ramp of cobalt-injected Drosophila for Fru circuit stimulation.
Fast thermal ramp of cobalt-injected and uninjected Drosophila for Fru circuit stimulation.
Multiplexed Drosophila Fru circuit stimulation.
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Sebesta, C., Torres Hinojosa, D., Wang, B. et al. Subsecond multichannel magnetic control of select neural circuits in freely moving flies. Nat. Mater. 21, 951–958 (2022). https://doi.org/10.1038/s41563-022-01281-7
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