[Active control of neural circuit synchrony via oligodendroglial lipid synthesis]

Myelin is increasingly recognized as a dynamic regulator of neural circuits, shifting the paradigm from a purely synaptic-centric view of brain plasticity. This report details how activity-dependent changes in myelin lipid composition optimize neural circuit synchrony during motor learning. Using a mouse model with subtle myelin structural deficits, we demonstrate that impaired myelin regulation leads to increased temporal dispersion of axonal conduction. This asynchrony reduces the signal-to-noise ratio of neural activity in the primary motor cortex, thereby hindering motor skill acquisition. Crucially, optogenetic synchronization of thalamocortical inputs rescues these learning deficits, confirming that temporal precision is vital for plasticity. Furthermore, imaging mass spectrometry revealed stage-specific shifts in myelin lipid composition during motor learning. Sphingomyelin levels rise during the early phase, while galactosylceramide levels increase during the middle-to-late stages. Targeted suppression of the galactosylceramide-synthesizing enzyme in oligodendrocytes specifically impairs late-stage learning and increases conduction asynchrony without affecting gross myelin morphology. These findings suggest that oligodendrocytes actively fine-tune the timing of information arrival by modulating the lipid composition of myelin. These dynamic changes in myelin lipid composition represent a novel perspective on white matter plasticity essential for optimizing neural circuit outputs and behavior, offering new insights into neuropsychiatric disorders characterized by impaired neural synchrony.