Magnetoelectric nanodiscs enable wireless transgene-free neuromodulation

Ye Ji Kim; Noah Kent; Emmanuel Vargas Paniagua; Nicolette Driscoll; Anthony Tabet; Florian Koehler; Elian Malkin; Ethan Frey; Marie Manthey; Atharva Sahasrabudhe; Taylor M Cannon; Keisuke Nagao; David Mankus; Margaret Bisher; Giovanni de Nola; Abigail Lytton-Jean; Lorenzo Signorelli; Danijela Gregurec; Polina Anikeeva

doi:10.1038/s41565-024-01798-9

Magnetoelectric nanodiscs enable wireless transgene-free neuromodulation

Nat Nanotechnol. 2024 Oct 11. doi: 10.1038/s41565-024-01798-9. Online ahead of print.

Authors

Ye Ji Kim^{1

2

3}, Noah Kent^#^{2

3}, Emmanuel Vargas Paniagua^#^{2

3}, Nicolette Driscoll^{2

3}, Anthony Tabet^{2

3}, Florian Koehler^{2

3

4}, Elian Malkin^{2

3

5}, Ethan Frey^{1

2

3}, Marie Manthey^{2

3}, Atharva Sahasrabudhe^{2

3

6}, Taylor M Cannon^{2

3}, Keisuke Nagao^{1

2

3}, David Mankus⁷, Margaret Bisher⁷, Giovanni de Nola⁷, Abigail Lytton-Jean⁷, Lorenzo Signorelli⁸, Danijela Gregurec⁸, Polina Anikeeva^{9

10

11

12}

Affiliations

¹ Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
² Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA.
³ McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁴ Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁵ Department Engineering in Computation and Cognition, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁶ Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁷ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁸ Department of Chemistry and Pharmacy, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
⁹ Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. anikeeva@mit.edu.
¹⁰ Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA. anikeeva@mit.edu.
¹¹ McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA. anikeeva@mit.edu.
¹² Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA. anikeeva@mit.edu.

^# Contributed equally.

PMID: 39394431
DOI: 10.1038/s41565-024-01798-9

Abstract

Deep brain stimulation with implanted electrodes has transformed neuroscience studies and treatment of neurological and psychiatric conditions. Discovering less invasive alternatives to deep brain stimulation could expand its clinical and research applications. Nanomaterial-mediated transduction of magnetic fields into electric potentials has been explored as a means for remote neuromodulation. Here we synthesize magnetoelectric nanodiscs (MENDs) with a core-double-shell Fe₃O₄-CoFe₂O₄-BaTiO₃ architecture (250 nm diameter and 50 nm thickness) with efficient magnetoelectric coupling. We find robust responses to magnetic field stimulation in neurons decorated with MENDs at a density of 1 µg mm^-2 despite individual-particle potentials below the neuronal excitation threshold. We propose a model for repetitive subthreshold depolarization that, combined with cable theory, supports our observations in vitro and informs magnetoelectric stimulation in vivo. Injected into the ventral tegmental area or the subthalamic nucleus of genetically intact mice at concentrations of 1 mg ml^-1, MENDs enable remote control of reward or motor behaviours, respectively. These findings set the stage for mechanistic optimization of magnetoelectric neuromodulation towards applications in neuroscience research.

Abstract

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