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

Takahiro Shimizu, Stuart G. Nayar, Matthew Swire, Yi Jiang, Matthew Grist, Malte Kaller, Cassandra Sampaio Baptista, David M. Bannerman, Heidi Johansen-Berg, Katsutoshi Ogasawara, Koujiro Tohyama, Huiliang Li and William D. Richardson ()
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Takahiro Shimizu: University College London
Stuart G. Nayar: University College London
Matthew Swire: University College London
Yi Jiang: University College London
Matthew Grist: University College London
Malte Kaller: University of Oxford
Cassandra Sampaio Baptista: University of Oxford
David M. Bannerman: University of Oxford
Heidi Johansen-Berg: University of Oxford
Katsutoshi Ogasawara: Iwate Medical University
Koujiro Tohyama: Iwate Medical University
Huiliang Li: University College London
William D. Richardson: University College London

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract Previous work has shown that motor skill learning stimulates and requires generation of myelinating oligodendrocytes (OLs) from their precursor cells (OLPs) in the brains of adult mice. In the present study we ask 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. We find that maze training stimulates OLP proliferation and OL production in the medial prefrontal cortex (mPFC), anterior corpus callosum (genu), dorsal thalamus and hippocampal formation of adult male mice; myelin sheath formation is also stimulated in the genu. Genetic blockade of OL differentiation and neo-myelination in Myrf conditional-knockout mice strongly impairs training-induced improvements in maze performance. We find a strong positive correlation between the performance of individual wild type mice and the scale of OLP proliferation and OL generation during training, but not with the number or intensity of c-Fos+ neurons in their mPFC, underscoring the important role played by OL lineage cells in cognitive processing.

Date: 2023
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DOI: 10.1038/s41467-023-42293-4

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