Microglia-neuron interaction at nodes of Ranvier depends on neuronal activity through potassium release and contributes to remyelination

Microglia, the resident immune cells of the central nervous system, are key players in healthy brain homeostasis and plasticity. In neurological diseases, such as Multiple Sclerosis, activated microglia either promote tissue damage or favor neuroprotection and myelin regeneration. The mechanisms for microglia-neuron communication remain largely unkown. Here, we identify nodes of Ranvier as a direct site of interaction between microglia and axons, in both mouse and human tissues. Using dynamic imaging, we highlight the preferential interaction of microglial processes with nodes of Ranvier along myelinated fibers. We show that microglia-node interaction is modulated by neuronal activity and associated potassium release, with THIK-1 ensuring their microglial read-out. Altered axonal K+ flux following demyelination impairs the switch towards a pro-regenerative microglia phenotype and decreases remyelination rate. Taken together, these findings identify the node of Ranvier as a major site for microglia-neuron interaction, that may participate in microglia-neuron communication mediating pro-remyelinating effect of microglia after myelin injury.

Erratum: Arnuti, F., et al. Sheep Dung Composition and Phosphorus and Potassium Release Affected by Grazing Intensity and Pasture Development Stage in an Integrated Crop-Livestock System. Agronomy 2020, 10, 1162

The authors would like to make the following correction to the published paper [...]

Critical role of anion on porous biochar structure and potassium release during potassium–assisted pyrolysis process

Potassium-assisted pyrolysis is an efficient approach of preparing versatile porous biochar. However, among potassium additives, it is hard to decide which is more applicable due to lack of understanding of...

Microglia-neuron communication at nodes of Ranvier depends on neuronal activity through potassium release and contributes to myelin repair

Microglia, the resident immune cells of the central nervous system, are key players in healthy brain homeostasis and plasticity. In neurological diseases, such as Multiple Sclerosis, activated microglia either promote tissue damage or favor neuroprotection and myelin regeneration. The mechanisms for microglia-neuron communication remain largely unkown. Here, we identify nodes of Ranvier as a direct and stable site of interaction between microglia and axons, in both mouse and human tissue. Using dynamic imaging, we highlight the preferential interaction of microglial processes with nodes of Ranvier along myelinated fibers. We show that microglianode interaction is modulated by neuronal activity and associated potassium release, with THIK-1 ensuring their microglial read-out. Disrupting axonal K+ flux following demyelination polarizes microglia towards a pro-inflammatory phenotype and decreases remyelination rate. Taken together, these findings identify the node of Ranvier as a major site for microglia-neuron communication, participating in the pro-remyelinating effect of microglia after myelin injury.