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.

Immunohistochemical Analysis of Myelin Structures.

Immunochemistry (immunocytochemistry for cells and immunohistochemistry for tissues) is a method used to label specific antigens, based on highly specific antibody-epitope interactions. The resulting labeling can be visualized and imaged through microscopy adapted to the type of detection system used (fluorophore, peroxidase, etc.). In the nervous system, myelin is a complex membrane structure, generated by myelinating glial cells, which ensheath axons and facilitate electrical conduction. Myelin alteration has been shown to occur in various neurological diseases, in which it is associated with functional deficits. Here, we focus on myelin detection by immunofluorescence using immunochemistry protocols based on antibodies directed against major myelin proteins.