RT Journal Article SR Electronic T1 Remote Deep Brain Stimulation by Transgene-free Magnetomechanical Approach JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.11.27.470141 DO 10.1101/2021.11.27.470141 A1 Chih-Lun Su A1 Ping-Hsiang Yen A1 Chao-Chun Cheng A1 Po-Han Chiang YR 2021 UL http://biorxiv.org/content/early/2021/11/27/2021.11.27.470141.abstract AB 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 absorption4, which makes it ideal for untethered DBS. Recently developed magnetogenetics have shown the potential of developing treatments for neurological disorders5. However, magnetogenetic approaches have potential side effects from overexpression of exogenous ion channels and gene delivery with viral vectors6,7. 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 brain8, 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.Competing Interest StatementThe authors have declared no competing interest.