Controlling the bioelectrical properties of neurons with ferritin-based Magnetogenetics

Abstract

Magnetogenetics promises remote control of neurons, but its validity is questioned due to controversies surrounding the underlying mechanisms and deficits in reproducibility. Recent studies discovered that ferritin, used in Magnetogenetics, transduces radiofrequency (RF) magnetic fields into biochemical signals (reactive oxygen species and oxidized lipids). Magnetic stimulation of ferritin-tethered TRPV channels induces Ca2+ responses and modulates behavior but electrophysiological studies indicate that a particular channel, Magneto2.0, is ineffective in affecting the neuronal bioelectrical properties. We investigated this problem using the Magnetogenetic technique FeRIC. We resolved the electromagnetic interference caused by RF in patch-clamp recordings and supported the data with voltage imaging experiments. In neurons expressing TRPV4FeRIC, RF depolarizes the membrane potential and increases the spiking frequency. In neurons expressing the chloride-permeable TMEM16AFeRIC, RF hyperpolarizes the membrane potential and decreases the spiking frequency. Our study reveals the control of neuronal bioelectrical properties with Magnetogenetics that is non-instantaneous, long-lasting, and moderate, but effective and comparable to that induced by endogenous signaling molecules.