Talk Title: Neuronal activity and immune cues modulate neuron-microglia communication at the node of Ranvier, shaping its role in repair
Abstract: Multiple Sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS). While an endogenous repair process exists following demyelination in MS, it is incomplete and varies between individuals. Understanding the mechanisms of remyelination and neuroprotection is therefore crucial to promote repair in patients. In MS, the nodes of Ranvier, which support the fast axonal conduction, are disrupted but can reorganize early during repair, even before remyelination proceeds. Furthermore, microglia, the central nervous system resident immune cells, are key players in the disease, as they can engage in pro-inflammatory as well as pro-regenerative processes. Our recent work identified nodal structures as a preferential site for microglia-neuron interaction in both mouse and human. We now demonstrate that neuronal activity promotes microglia-node interaction and the switch towards pro-regenerative microglia. Conversely, adaptive immune cues impair microglia-node interaction in an inflammatory MS model and the extent of these interactions at the onset of remission correlates with recovery. Taken together, our findings identify factors that influence microglia-neuron crosstalk in disease and suggest that neuronal activity supports remyelination not only by directly regulating oligodendroglia, but also by modulating microglial behavior during repair.