CROSSTALK BETWEEN DEVELOPING OLIGODENDROCYTES AND AXONS

Oligodendrocytes, namely glial cells in the central nervous system (CNS) responsible for myelin sheath formation around axons, play a key role in the establishment and maintenance of functional neuronal networks. Recent evidence indicates that myelination is an adaptive process modulated by neuronal activity, while oligodendrocyte intracellular calcium has emerged as a critical mediator of both activity-dependent and activity-independent myelin plasticity. Here, we investigate the crosstalk between neuronal activity and oligodendrocyte calcium dynamics under physiological and pathological conditions. Using spinal cord organotypic cultures, a biological CNS model that preserves that preserve tissue architecture and functional connectivity, we combine immunohistochemistry with live imaging based on oligodendrocyte-specific genetically encoded calcium indicators to monitor oligodendroglial activity. Neuroinflammation is induced using a cytokine cocktail that recapitulates key inflammatory features observed in vivo. Our results show that inflammatory conditions impair oligodendrocyte differentiation and reduce myelin basic protein expression. Moreover, inflammation induces prolonged calcium transients in myelinating oligodendrocytes that become uncoupled from neuronal activity, indicating a disruption of activity-dependent axon–oligodendrocyte signaling that may contribute to myelin dysfunction. Ongoing work focuses on characterizing the spatiotemporal dynamics of oligodendrocyte intracellular calcium using a state-of-the-art analytical pipeline, while establishing combined recordings of axonal voltage, via a genetically encoded voltage indicator, and calcium activity in ensheathing oligodendrocyte processes during myelination and demyelination. Overall, this approach provides a mechanistic framework to understand how neuronal activity and inflammation shape oligodendrocyte calcium signaling and myelin plasticity, and may help identify activity-dependent processes that could be targeted to promote remyelination under pathological conditions