Magnetoelectric nanodiscs enable wireless transgene-free neuromodulation
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.
Deep brain stimulation (DBS) via surgically implanted electrodes is a powerful therapeutic tool for neurological and psychiatric conditions1. Less invasive neuromodulation alternatives have been developed on the basis of transcranial magnetic stimulation2, temporal interference electrical stimulation3,4, focused ultrasound5,6,7 and optogenetics with external light sources8,9. In addition, weak magnetic fields (MFs) have been leveraged to deliver signals to deep brain structures owing to the low conductivity and magnetic permeability of biological matter10. MFs have been transduced into mechanical torque11,12, heat13,14,15,16 and chemical release17,18 enabling modulation of cells expressing mechano-, thermo- and chemo-receptors, respectively. Although genetic sensitization of identifiable cells to specified stimuli empowers fundamental neuroscience research, the need for transgenes impeded the implementation of these methods in translational and clinical studies.
