Calcium is a key intracellular messenger that regulates many vital cellular processes. Calcium signals in oligodendrocytes, the myelinating glia of the CNS, are known to translate environmental information to cellular processes such as proliferation, differentiation and myelination. Myelination is an adaptive process that depends on neuronal activity. We recently demonstrated that neuronal activity in vivo enhances remyelination in demyelinated lesions (Ortiz et al., 2019, JCI Insight). Here, we investigate whether calcium singal in oligodendroglia play a role in remyelination and whether behavioral intervention improves this process. We are using PDGF-CreERT;Gcamp6f/f mice to perform ex vivo and in vivo calcium imaging of oligodendroglial during myelin repair using demyelination/remyelination models. On the one hand, ex vivo brain slices are used to determine the calcium signaling mechanisms and, on the other hand, in vivo microendoscopy is used to analyze calcium signals during behavioral tasks. We have recently set up all the experimental and analytical framework for the analysis of ex vivo and in vivo calcium signals in oligodendroglia (Maas et al., 2024, Cell Mol Life Sci). Preliminary data indicates that calcium signals ex vivo and in vivo are high in lesion conditions. We are currently analysing the intracellular calcium dynamics at different time points of the demyelination and remyelination process. This project should shed light on the role of calcium activity in oligodendroglia during myelin repair and, as such, contribute to our understanding of the repair mechanisms in the context of demyelinating diseases such as multiple sclerosis.