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The importance of specific neurons to a network’s 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.

Central to understanding membrane bound cell signaling is to quantify how the membrane ultra-structure consisting of transient spatial domains modulates signaling and how the signaling influences this ultra-structure. Yet, measuring the association of membrane proteins with domains in living, intact cells poses considerable challenges. Here, we describe a non-destructive method to quantify protein-lipid domain and protein cytoskeleton interactions in single, intact cells enabling continuous monitoring of the protein domains interaction over time during signaling., Comment: 13 pages, 5 figures, currently being reviewed by journal