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Subsecond multichannel magnetic control of select neural circuits in freely moving flies

Nature Materials volume 21, pages 951–958 (2022)Cite this article

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Abstract

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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Fig. 1: Behavioural fly assay.
Fig. 2: Rate response of magnetogenetic stimulation of cells expressing fruitless at subsecond response time.
Fig. 3: Versatility of magnetothermal stimulation in secondary cell type expressing Hb-9.
Fig. 4: Multiplexed magnetothermal heating of nanoparticles.
Fig. 5: Multichannel magnetogenetic stimulation of cells expressing fruitless.

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Data availability

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.

Code availability

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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Acknowledgements

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.

Author information

Authors and Affiliations

  1. Department of Bioengineering, Rice University, Houston, TX, USA

    Charles Sebesta, Daniel Torres Hinojosa, Kaiyi Jiang, Linlin Zhang, Qingbo Zhang, Gang Bao & Jacob T. Robinson

  2. Department of Psychiatry & Behavioral Sciences, School of Medicine, Duke University, Durham, NC, USA

    Boshuo Wang, Stefan M. Goetz & Angel V. Peterchev

  3. Department of Electrical and Computer Engineering, Rice University, Houston, TX, USA

    Joseph Asfouri, Guillaume Duret & Jacob T. Robinson

  4. Department of Electrical and Computer Engineering, School of Engineering, Duke University, Durham, NC, USA

    Zhongxi Li, Stefan M. Goetz & Angel V. Peterchev

  5. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Kaiyi Jiang

  6. Department of Chemistry, Brown University, Providence, RI, USA

    Zhen Xiao & Vicki L. Colvin

  7. Department of Neurosurgery, School of Medicine, Duke University, Durham, NC, USA

    Stefan M. Goetz & Angel V. Peterchev

  8. Institute of Brain Sciences, Duke University, Durham, NC, USA

    Stefan M. Goetz

  9. Department of Engineering, School of Technology, University of Cambridge, Cambridge, UK

    Stefan M. Goetz

  10. Department of Biomedical Engineering, School of Engineering, Duke University, Durham, NC, USA

    Angel V. Peterchev

  11. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    Herman A. Dierick

  12. Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA

    Herman A. Dierick & Jacob T. Robinson

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Contributions

C.S. designed, performed and analysed the in vivo behavioural assays for Drosophila. D.T.H. synthesized, coated, functionalized and characterized iron oxide nanoparticles and low-SLP and cobalt-doped nanoparticles. K.J. prepared nanoparticles for testing and L.Z. assisted with heating measurements. Z.X. and Q.Z. synthesized and characterized iron oxide nanoclusters. C.S. and D.T.H. recorded SLP measurements of nanoparticles and nanoclusters. C.S. and H.A.D. designed and performed the nanoparticle injection scheme for adult Drosophila. B.W. and Z.L. designed and built the custom AMF system used for in vivo recordings and the magnetic field driver used for the ac magnetometer. J.A. built the ac magnetometer and recorded dynamic hysteresis loops. C.S. and J.A. performed thermal imaging experiments. J.T.R., H.A.D. and G.D. contributed to the design of the experiments. H.A.D. and J.T.R. supervised behavioural assay design and development. S.M.G. and A.V.P. supervised AMF system design and development. V.L.C. and G.B. supervised nanoparticle synthesis, characterization and functionalization. C.S., D.T.H., B.W., J.A., J.T.R. and H.A.D. prepared the manuscript with input from all authors.

Corresponding author

Correspondence to Jacob T. Robinson.

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Competing interests

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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Nature Materials thanks Michael Christiansen, Andre Fiala and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–12 and video legends.

Reporting Summary

Supplementary Video 1

Slow thermal ramp of cobalt-injected Drosophila for Fru circuit stimulation.

Supplementary Video 2

Fast thermal ramp of cobalt-injected and uninjected Drosophila for Fru circuit stimulation.

Supplementary Video 3 Drosophila Hb9 circuit stimulation with low-SLP SPION-injected controls.

Supplementary Video 4

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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