Electrified Microglia: Impact Of Direct Current Stimulation On Diverse Properties Of The Most Versatile Brain Cell

Background: Transcranial direct current stimulation [(t)DCS], modulates cortical excitability and promotes neuroplasticity. Microglia has been identified to respond to electrical currents as well as neuronal activity, but its response to DCS is mostly unknown.Objective: This study addresses effects of DCS applied in vivo to the sensorimotor cortex on physiological microglia properties and neuron-microglia communication.Methods: Time lapse in vivo 2-photon microscopy in anaesthetized mice was timely coupled with DCS of the sensorimotor cortex to observe microglia dynamics on a population-based and single cell level. Neuron-microglia communication during DCS was investigated in mice with a functional knock out of the fractalkine receptor CX3CR1. Moreover, the role of voltage gated microglial channels and DCS effects on phagocytosis were studied.Results: DCS promoted several physiological microglia properties, depending on the glial activation state and stimulation intensity. On a single cell level, process motility was predominantly enhanced in ramified cells whereas horizontal soma movement and galvanotaxis was pronounced in reactive microglia. Blockage of voltage sensitive microglial channels suppressed DCS effects in vivo and in vitro. Microglial motility changes were partially driven by the fractalkine signaling pathway. Moreover, phagocytosis increased after DCS in vitro.Conclusion: Microglia dynamics are rapidly influenced by DCS. This is the first in vivo demonstration of a direct effect of electrical currents on microglia and indirect effects potentially driven by neuronal activity via the fractalkine pathway. (C) 2021 Published by Elsevier Inc.