Bidirectional Magnetothermal Modulation of Neuronal Activity in Behaving Mice

Abstract

Reversible modulation of targeted neuronal population holds great potential in neurological pathology and therapeutics. Previously, we have shown that neurons thermo-sensitized by TRPV1 channel expression (via AAV5), can be reversibly magneto-thermally stimulated by heating membrane bound super-paramagnetic nanoparticles with alternating magnetic fields. In vivo, this evokes specific behaviors. Here, we show that silencing may be achieved similarly by localized magnetothermal heating of the membrane. Action potential generation involves a series of ion-channel opening and closing. These are intrinsically temperature sensitive, and we show here that it is possible to reversibly suppress neuronal firing by transient temperature rises. We systematically evaluated thermo-modulation in wild type dissociated neurons in a temperature bath, and show how silencing is a function of temperature-increase rates as well as the absolute temperature. We demonstrate that this magneto-thermal neurosilencing can evoke specific behaviors in a place preference assay (PPA). Given a choice, mice prefer a dark chamber over a lit one. We show that magneto-thermal inactivation of Dopaminergic (DA) neurons in the ventral tegmental area (VTA) affects this PPA choice of these mice. Our results show that selective thermo-modulation is a powerful all-round tool for remotely modulating animal behavior. This principle and toolset can be seamlessly expanded to counter addiction causing memory formations. It might also act as a tetherless alternative to optogenetic tools for studying social behavior as well as cognitive memory and learning pathways.