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Marcellino, D.

Publications and source records attributed to Marcellino, D..

2 recordsLinked to original sources

Learning-related contraction of grey matter in rodent sensorimotor cortex is associated with adaptive myelination

From observations in rodents, it has been suggested that the cellular basis of learning-dependent changes, detected using structural magnetic resonance imaging (MRI), may be increased dendritic spine density, alterations in astrocyte volume, and adaptations within intracortical myelin. Myelin plasticity is crucial for neurological function and active myelination is required for learning and memory. However, the dynamics of myelin plasticity and how it relates to morphometric-based measurements of structural plasticity remains unknown. We used a motor skill learning paradigm to evaluate experience-dependent brain plasticity by voxel-based morphometry (VBM) in longitudinal MRI, combined with a cross-sectional immunohistochemical investigation. Whole brain VBM revealed non-linear decreases in grey matter (GM) juxtaposed to non-linear increases in white matter (WM) that were best modelled by an asymptotic time course. Using an atlas-based cortical mask, we found non-linear changes with learning in primary and secondary motor areas and in somatosensory cortex. Analysis of cross-sectional myelin immunoreactivity in forelimb somatosensory cortex confirmed an increase in myelin immunoreactivity followed by a return towards baseline levels. The absence of significant histological changes in cortical thickness further suggests that non-linear morphometric changes are likely due to changes in intracortical myelin for which morphometric WM volume (WMV) data significantly correlated with myelin immunoreactivity. Together, these observations indicate a non-linear increase of intracortical myelin during learning and support the hypothesis that myelin is a component of structural changes observed by VBM during learning.

neuroscience↗

Whole-brain fluorescence-MRI coregistration for precise anatomical mapping of virus infection

Viral tropism within the brain and the role(s) of vertebrate immune response to neurotropic flaviviruses infection is largely understudied. We combined multimodal imaging (cm-nm scale) with single nuclei RNA- sequencing to study Langat virus in wildtype and interferon alpha/beta receptor knockout (Ifnar-/-) mice to visualize viral pathogenesis and define molecular mechanisms. Whole brain viral infection was imaged by Optical Projection Tomography coregistered to ex vivo MRI. Infection was limited to grey matter of sensory systems in wildtype mice, but extended into white matter, meninges and choroid plexus in Ifnar-/-mice. Cells in wildtype displayed strong type I and II IFN responses, likely due to Ifnb expressing astrocytes, infiltration of macrophages and Ifng-expressing CD8+NK cells, whereas in Ifnar-/-, the absence of this response contributed to a shift in cellular tropism towards non-activated resident microglia. Multimodal imaging-transcriptomics exemplifies a powerful way to characterize mechanisms of viral pathogenesis and tropism.

microbiology↗