Various magnetic deep brain stimulation (DBS) methods have been developing rapidly in the last decade for minimizing the invasiveness of DBS. However, current magnetic DBS methods, such as magnetothermal and magnetomechanical stimulation, require overexpressing exogeneous ion channels in the central nervous system (CNS). It is unclear whether magnetomechanical stimulation can modulate non-transgenic CNS neurons or not. Here, we reveal that the torque of magnetic nanodiscs with weak and slow alternative magnetic field (50 mT at 10 Hz) could activate neurons through the intrinsic transient receptor potential canonical channels (TRPC), which are mechanosensitive ion channels widely expressed in the brain. The immunostaining with c-fos shows the increasement of neuronal activity by wireless DBS with magnetomechanical approach in vivo. Overall, this research demonstrates a magnetic nanodiscs-based magnetomechanical approach that can be used for wireless neuronal stimulation in vitro and untethered DBS in vivo without implants or genetic manipulation.
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.
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