Microwaves stimulate and inhibit neurons via modulation of TRPV and TREK channels

OBJECTIVE: Electrical neuromodulation, the current clinical standard, is invasive, expensive, and prone to malfunction. Electromagnetic waves can perform noninvasive neuromodulation, but existing methods are limited by the tradeoff between penetration depth and spatial precision. Microwaves in the 0.9 - 3 GHz range are widely used for telecommunications and can penetrate to the deep brain. Microwaves have been shown to nonthermally modulate neural activity, but the acute cellular bioeffects remain unclear and under-studied. APPROACH: Here, we employ a miniaturized microwave-powered neuromodulation implantable device (MINI) to investigate the roles of ion channels in microwave-mediated thermal stimulation and nonthermal inhibition. The MINI enabled electrophysiological recordings of neurons exposed to microwaves, which elucidated the differential effects of pulsed and continuous microwaves on neurons. We further investigated the cellular mechanisms of microwave neuromodulation using voltage imaging and channel blockers. MAIN RESULTS: We determined that inhibition occurs via nonthermal upregulation of TREK-1 channel activity while stimulation occurs via thermal activation of TRPV-1 channels. SIGNIFICANCE: These findings build the foundation for developing microwave-based wireless neuromodulation devices for drug-free treatment of seizures and chronic pain. Additionally, they provide a basis for nonthermal microwave bioeffects which should be considered when setting exposure limits.