Deep Brain Magnetothermal Silencing of Dopaminergic Neurons via Endogenous TREK1 Channels Abolishes Place Preference in Mice

Abstract

AbstractReversible silencing of neuronal activity in freely behaving animals provides a powerful tool to determine the roles of specific neuronal populations in circuit dynamics and behavior. Here, we show how magnetothermal silencing using endogenous TREK-1 channels can suppress the dopaminergic reward in the ventral tegmental area and the place preference in mice.Magnetothermal silencing uses alternating magnetic fields penetrating tissue undiminished without harmful effects to heat superparamagnetic nanoparticles at the target cells. The induced sudden, small increase in temperature inhibits neuronal firing rapidly and reversibly, and without the need of genetic modification of the neurons. We demonstrate that two-pore potassium channel TREK-1 channels are responsible for this thermal neuronal silencing. Using fiber-based optogenetics we measure the heating and neuronal silencing in the ventral tegmental area (VTA) brain of the animals. We show that in a place preference assay magnetothermal neuronal silencing of the dopaminergic neurons in the VTA is sufficient to abolished the place preference. TREK1 knock-out mice are immune to the magnetothermal silencing and behave as if the magnetic field were not applied.HighlightsTREK1 is a highly efficient, thermally activated neuronal silencerFirst magnetothermal neuronal silencing in behaving miceFiber photometry determination of local heating and silencing of target neurons in the ventral tegmental areaMagnetothermal suppression of dopaminergic reward response in the ventral tegmental area is sufficient to abolish place preference