Magnetoelectric Nanodiscs Enable Wireless Transgene-Free Neuromodulation

Deep-brain stimulation (DBS) with implanted electrodes revolutionized treatment of movement disorders and empowered neuroscience studies. Identifying less invasive alternatives to DBS may further extend its clinical and research applications. Nanomaterial-mediated transduction of magnetic fields into electric potentials offers an alternative to invasive DBS. Here, we synthesize magnetoelectric nanodiscs (MENDs) with a core-double shell Fe3O4-CoFe2O4-BaTiO3 architecture with efficient magnetoelectric coupling. We find robust responses to magnetic field stimulation in neurons decorated with MENDs at a density of 1 µg/mm2 despite individual-particle potentials below the neuronal excitation threshold. We propose a model for repetitive subthreshold depolarization, which combined with cable theory, corroborates our findings in vitro and informs magnetoelectric stimulation in vivo. MENDs injected into the ventral tegmental area of genetically intact mice at concentrations of 1 mg/mL enable remote control of reward behavior, setting the stage for mechanistic optimization of magnetoelectric neuromodulation and inspiring its future applications in fundamental and translational neuroscience. ### Competing Interest Statement Ye Ji Kim, Florian Koehler, and Polina Anikeeva have applied for a provisional US patent related to the magnetoelectric nanodisc technology reported in the manuscript.