The role of microglia membrane potential in chemotaxis

Microglia react to danger signals by rapid and targeted extension of cellular processes towards the source of the signal. This positive chemotactic response is accompanied by a hyperpolarization of the microglia membrane. Here, we show that optogenetic depolarization of microglia has little effect on baseline motility, but significantly slows down the chemotactic response. Reducing the extracellular Ca(2+) concentration mimics the effect of optogenetic depolarization. As the membrane potential sets the driving force for Ca(2+) entry, hyperpolarization is an integral part of rapid stimulus-response coupling in microglia. Compared to typical excitable cells such as neurons, the sign of the activating response is inverted in microglia, leading to inhibition by depolarizing channelrhodopsins. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-020-02048-0.