Long-term in vivo three-photon imaging reveals region-specific differences in healthy and regenerative oligodendrogenesis.
Michael A ThorntonGregory L FutiaMichael E StocktonSamuel A BudoffAlexandra N RamirezBaris N OzbayOmer TzangKarl KilbornAlon Poleg-PolskyDiego RestrepoEmily A GibsonEthan G HughesPublished in: Nature neuroscience (2024)
The generation of new myelin-forming oligodendrocytes in the adult central nervous system is critical for cognitive function and regeneration following injury. Oligodendrogenesis varies between gray and white matter regions, suggesting that local cues drive regional differences in myelination and the capacity for regeneration. However, the layer- and region-specific regulation of oligodendrocyte populations is unclear due to the inability to monitor deep brain structures in vivo. Here we harnessed the superior imaging depth of three-photon microscopy to permit long-term, longitudinal in vivo three-photon imaging of the entire cortical column and subcortical white matter in adult mice. We find that cortical oligodendrocyte populations expand at a higher rate in the adult brain than those of the white matter. Following demyelination, oligodendrocyte replacement is enhanced in the white matter, while the deep cortical layers show deficits in regenerative oligodendrogenesis and the restoration of transcriptional heterogeneity. Together, our findings demonstrate that regional microenvironments regulate oligodendrocyte population dynamics and heterogeneity in the healthy and diseased brain.
Keyphrases
- white matter
- high resolution
- stem cells
- multiple sclerosis
- mesenchymal stem cells
- single cell
- living cells
- cell therapy
- gene expression
- traumatic brain injury
- type diabetes
- optical coherence tomography
- single molecule
- young adults
- childhood cancer
- oxidative stress
- photodynamic therapy
- fluorescence imaging
- high speed
- functional connectivity