Magnetic Nanoparticle-Based Mechanical Stimulation for Restoration of Mechano-Sensitive Ion Channel Equilibrium in Neural Networks

Techniques offering remote control of neural activity with high spatiotemporal resolution and specificity are invaluable for deciphering the physiological roles of different classes of neurons in brain development and disease. Here, we first confirm that microfabricated substrates with enhanced magnetic field gradients allow for wireless stimulation of neural circuits dosed with magnetic nanoparticles using calcium indicator dyes. We also investigate the mechanism of mechano-transduction in this system and identify that N-type mechano-sensitive calcium ion channels play a key role in signal generation in response to magnetic force. We next applied this method for chronic stimulation of a fragile X syndrome (FXS) neural network model and found that magnetic force-based stimulation modulated the expression of mechano-sensitive ion channels which are out of equilibrium in a number of neurological diseases including FXS. This technique can serve as a tool for acute and chronic modulation of endogenous ion channel expression in neural circuits in a spatially localized manner to investigate a number of disease processes in the future.