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

Remote neuromodulation techniques have revolutionized our understanding of brain circuits and their role in behavior. The reversible silencing of specific neuronal populations has emerged as a powerful tool to investigate the necessity and sufficiency of these populations in behavioral responses. Here, we apply magnetothermal silencing using endogenous TREK-1 channels to selectively suppress dopaminergic reward in the ventral tegmental area (VTA) to prove that activation of this specific reward circuit is required for place preference in mice. Magnetothermal silencing entails the application of alternating magnetic fields that penetrate tissue, leading to the heating of superparamagnetic nanoparticles at the target cells, without causing any attenuation or adverse effects. The resultant slight, rapid, and reversible elevation in temperature effectively suppresses neuronal firing, without necessitating genetic modification of the neurons. We demonstrate that two-pore potassium channels, TREK-1, are responsible for this thermal neuronal silencing. Using fiber-based optogenetics we measured both the heating and neuronal silencing in the 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 abolish the place preference. Notably, TREK1 knock-out mice exhibit immunity to magnetothermal silencing, behaving as if the magnetic field was not applied. These results underscore the critical role of dopaminergic neuronal activity in the VTA for the establishment of place preference and highlight the dependency on functional TREK1 channels in this magnetothermal silencing approach. HighlightsO_LITREK1 is a highly efficient, thermally activated neuronal silencer C_LIO_LIFirst magnetothermal neuronal silencing in behaving mice C_LIO_LIFiber photometry quantification of local heating and silencing of target neurons in the ventral tegmental area C_LIO_LIMagnetothermal suppression of dopaminergic reward response in the ventral tegmental area is sufficient to abolish place preference C_LI