Remote Deep Brain Stimulation by Transgene-free Magnetomechanical Approach

Abstract Various physical stimulation methods are developed to minimize the invasiveness of deep brain stimulation (DBS) 1–3 . Among them, only magnetic field can penetrate into the biological tissues without scattering or absorption 4 , which makes it ideal for untethered DBS. Recently developed magnetogenetics have shown the potential of developing treatments for neurological disorders 5 . However, magnetogenetic approaches have potential side effects from overexpression of exogenous ion channels and gene delivery with viral vectors 6,7 . Here, we demonstrated that the iron oxide magnetic nanodiscs (~270 nm) can be used as transducers to trigger calcium responses in the wild-type cultured neurons during the application of slow varying weak magnetic fields (50 mT at 10 Hz). Moreover, we identified that the intrinsic mechanosensitive ion channel transient receptor potential canonical (TRPC), which were widely expressed in the brain 8 , plays the main roles in this magnetomechanical stimulation. Finally, when we applied magnetic fields to the awake mice with magnetic nanodiscs injecting into subthalamic nucleus, the magnetomechanical stimulation triggered neuronal activities in the targeted region and the downstream region. Overall, this research demonstrated a magnetomechanical approach that can be used for wireless neuronal stimulation in vitro and untethered DBS in awake mice in vivo without implants or genetic manipulation.