Oligodendrocyte dynamics dictate individual performance outcomes of working memory training in mice

Motor skill learning stimulates and requires generation of myelinating oligodendrocytes (OLs) from their precursors. We asked whether OL production is also required for non-motor learning and cognition, using T-maze and radial arm maze tasks that tax spatial working memory. Maze training stimulated OL production in the medial prefrontal cortex, anterior corpus callosum (genu), hippocampus and fimbria; myelin sheath formation was also stimulated in the genu. Genetic blockade of OL differentiation and neo-myelination in Myrf conditional knockout mice strongly impaired training-induced improvements in maze performance. Remarkably, working memory performance of individual mice correlated closely with the scale of OL precursor proliferation and OL generation in their genu and anterior cingulate cortex during training, indicating a key role for adaptive OL genesis and myelination in cognitive processing. ### Competing Interest Statement The authors have declared no competing interest.