Mediavilla, T. | bioRxiv Science

bioRxiv2022

An MR-based brain template and atlas for optical projection tomography and light sheet fluorescence microscopy

Optical projection tomography (OPT) and light sheet fluorescence microscopy (LSFM) are high-resolution optical imaging techniques operating in the mm-cm range, ideally suited for ex vivo 3D whole mouse brain imaging. Although these techniques exhibit high sensitivity and specificity for antibody-labeled targets, the provided anatomical information remains limited. To allow anatomical mapping of fluorescent signal in whole brain, we developed a novel magnetic resonance (MR) - based template with its associated tissue priors and atlas labels, specifically designed for brains subjected to tissue processing protocols required for 3D optical imaging. We investigated the effect of tissue pre-processing and clearing on brain size and morphology and developed optimized templates for BABB/Murrays clear (OCUM) and DBE/iDISCO (iOCUM) cleared brains. By creating optical-(i)OCUM fusion images using our mapping procedure, we localized dopamine transporter and translocator protein expression and tracer innervation from the eye to the lateral geniculate nucleus of thalamus and superior colliculus. These fusion images allowed for precise anatomical identification of fluorescent signal in discrete brain areas. As such, these templates enable applications in a broad range of research areas integrating optical 3D brain imaging by providing an MR template for cleared brains.

neuroscience↗

bioRxiv2022

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↗