Transient Magnetothermal Neuronal Silencing using the Chloride Channel Anoctamin1 (TMEM16A)

Abstract

The importance of specific neurons to a networks function is best studied by precisely timed, reversible silencing of these neurons. Previously, we showed that alternating magnetic field mediated heating of magnetic nanoparticles bound to neurons expressing temperature-sensitive cation channels TRPV1, stimulates these neurons to fire and affects animal behavior in vivo (Munshi et al., 2017). Here, we demonstrate how to apply magnetic nanoparticle mediated heating to silence target neurons. Rat hippocampal neuron cultures are transfected to express the temperature gated chloride Anoctamin1 (TMEM16A) channels. Within seconds the heating of the membrane opens the Anoctamin1 (TMEM16A) channels, suppressing action potential firing. Five seconds of magnetic field application leads to about 12 seconds of silencing, with a latency of about 2 seconds and an average suppression ratio of more than 80%. The method provides a promising avenue for tether free, remote, transient neuronal silencing in vivo for both scientific and therapeutic applications.