Learning-related contraction of grey matter in rodent sensorimotor cortex is associated with adaptive myelination
- Umeå University, Sweden
- Karolinska Institute, Sweden
- University of Gothenburg, Sweden
Abstract
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 in male mice 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 volume (GMV) juxtaposed to non-linear increases in white matter volume (WMV) within GM 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. Further investigations using quantitative confocal microscopy confirmed these changes specifically to the length density of myelinated axons. The absence of significant histological changes in cortical thickness suggests that non-linear morphometric changes are likely due to changes in intracortical myelin for which morphometric WMV in somatosensory cortex 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.
Data availability
The structural MRI raw data and the scripts employed for the image processing and analysis have been uploaded to Dryad. All these files are provided together with an explanatory document that would allow to reproduce our results.
-
Skilled Reaching Structural MRIDryad, doi:10.5061/dryad.crjdfn36c.
Article and author information
Author details
Daniel J Marcellino
Funding
StratNeuro
- Daniel J Marcellino
Kempestiftelserna (JCK-1922.2)
- Fahad R Sultan
- Daniel J Marcellino
Insamlingsstiftelsen för medicinsk forskning Umeå Universitet
- Daniel J Marcellino
Magnus Bergvalls Stiftelse (2016-01639)
- Daniel J Marcellino
Vetenskapsrådet (2015-01717)
- Claudio Brozzoli
Agence Nationale de la Recherche (ANR-16-CE28-0008-01)
- Claudio Brozzoli
Agencia Canaria de Investigación, Innovación y Sociedad de la Información
- Héctor Martín Estévez-Silva
Umeå University Medical Faculty
- Daniel J Marcellino
Vetenskapsrådet (2018-01047)
- Martin Lövdén
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures involving animals were in accordance with protocols approved by the Umeå Regional Ethics Committee for Animal Research (ethical permit: Dnr A 35/2016).
Copyright
© 2022, Mediavilla et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,323
- views
-
- 216
- downloads
-
- 11
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Learning-related contraction of grey matter in rodent sensorimotor cortex is associated with adaptive myelination
eLife 11:e77432.
https://doi.org/10.7554/eLife.77432
Further reading
-
- Evolutionary Biology
- Neuroscience
The first complete 3D reconstruction of the compound eye of a minute wasp species sheds light on the nuts and bolts of size reduction.
-
- Neuroscience
Early-life stress can have lifelong consequences, enhancing stress susceptibility and resulting in behavioural and cognitive deficits. While the effects of early-life stress on neuronal function have been well-described, we still know very little about the contribution of non-neuronal brain cells. Investigating the complex interactions between distinct brain cell types is critical to fully understand how cellular changes manifest as behavioural deficits following early-life stress. Here, using male and female mice we report that early-life stress induces anxiety-like behaviour and fear generalisation in an amygdala-dependent learning and memory task. These behavioural changes were associated with impaired synaptic plasticity, increased neural excitability, and astrocyte hypofunction. Genetic perturbation of amygdala astrocyte function by either reducing astrocyte calcium activity or reducing astrocyte network function was sufficient to replicate cellular, synaptic, and fear memory generalisation associated with early-life stress. Our data reveal a role of astrocytes in tuning emotionally salient memory and provide mechanistic links between early-life stress, astrocyte hypofunction, and behavioural deficits.
