Abstract
Atomic force microscopy (AFM) is emerging as an innovative tool to phenotype the brain. This study demonstrates the utility of AFM to determine nanomechanical and nanostructural features of the murine dorsolateral frontal cortex from weaning to adulthood. We found an increase in tissue stiffness of the primary somatosensory cortex with age, along with an increased cortical mechanical heterogeneity. To characterize the features potentially responsible for this heterogeneity, we applied AFM scan mode to directly image the topography of thin sections of the primary somatosensory cortical layers II/III, IV and V/VI. Topographical mapping of the cortical layers at successive ages showed progressive smoothing of the surface. Topographical images were also compared with histochemically derived morphological information, which demonstrated the deposition of perineuronal nets, important extracellular components and markers of maturity. Our work demonstrates that high-resolution AFM images can be used to determine the nanostructural properties of cortical maturation, well beyond embryonic and postnatal development. Furthermore, it may offer a new method for brain phenotyping and screening to uncover topographical changes in early stages of neurodegenerative diseases.
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Acknowledgements
We thank Randall Willis and Laure Verret for critically reading the manuscript. We thank Cedric Baudelin and Lionel Mouledous for their technical expertise. We thank Lucie Fontaine at the Histology Platform (I2MC), and, Yvan Nicaise and Mélanie Pucelle at the Imaging Platform (CMEAB). This work was supported by the “Fondation pour la Recherche Médicale” (G.S.; Grant ING21040129094) and by the “les initiatives d’excellence” at the University de Toulouse (IDEX, S11V9R49). ED and DA are researchers at the Centre National de la Recherche Scientifique (CNRS).
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Smolyakov, G., Dague, E., Roux, C. et al. Nanoscale structural mapping as a measure of maturation in the murine frontal cortex. Brain Struct Funct 223, 255–265 (2018). https://doi.org/10.1007/s00429-017-1486-z
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DOI: https://doi.org/10.1007/s00429-017-1486-z