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

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.

The following data sets were generated

Article and author information

Author details

  1. Tomas Mediavilla

    Department of Integrative Medical Biology, Umeå University, Umeå, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  2. Özgün Özalay

    Department of Integrative Medical Biology, Umeå University, Umeå, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  3. Héctor Martín Estévez-Silva

    Department of Integrative Medical Biology, Umeå University, Umeå, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  4. Bárbara Frias

    Department of Integrative Medical Biology, Umeå University, Umeå, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  5. Greger Orädd

    Department of Integrative Medical Biology, Umeå University, Umeå, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  6. Fahad R Sultan

    Department of Integrative Medical Biology, Umeå University, Umeå, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  7. Claudio Brozzoli

    Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Solna, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  8. Benjamín Garzón

    Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Solna, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  9. Martin Lövdén

    Department of Psychology, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  10. Daniel J Marcellino

    Department of Integrative Medical Biology, Umeå University, Umeå, Sweden
    For correspondence
    daniel.marcellino@umu.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4618-7267

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

  • 1,357
    views
  • 219
    downloads
  • 16
    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)

  1. Tomas Mediavilla
  2. Özgün Özalay
  3. Héctor Martín Estévez-Silva
  4. Bárbara Frias
  5. Greger Orädd
  6. Fahad R Sultan
  7. Claudio Brozzoli
  8. Benjamín Garzón
  9. Martin Lövdén
  10. Daniel J Marcellino
(2022)
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

Share this article

https://doi.org/10.7554/eLife.77432

Further reading

    1. Neuroscience
    Ulrike Pech, Jasper Janssens ... Patrik Verstreken
    Research Article

    The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence of nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to the emergence of motor issues, patients frequently experience non-motor symptoms, such as a reduced sense of smell (hyposmia). The cellular and molecular bases for these early defects remain enigmatic. To explore this, we developed a new collection of five fruit fly models of familial Parkinsonism and conducted single-cell RNA sequencing on young brains of these models. Interestingly, cholinergic projection neurons are the most vulnerable cells, and genes associated with presynaptic function are the most deregulated. Additional single nucleus sequencing of three specific brain regions of Parkinson’s disease patients confirms these findings. Indeed, the disturbances lead to early synaptic dysfunction, notably affecting cholinergic olfactory projection neurons crucial for olfactory function in flies. Correcting these defects specifically in olfactory cholinergic interneurons in flies or inducing cholinergic signaling in Parkinson mutant human induced dopaminergic neurons in vitro using nicotine, both rescue age-dependent dopaminergic neuron decline. Hence, our research uncovers that one of the earliest indicators of disease in five different models of familial Parkinsonism is synaptic dysfunction in higher-order cholinergic projection neurons and this contributes to the development of hyposmia. Furthermore, the shared pathways of synaptic failure in these cholinergic neurons ultimately contribute to dopaminergic dysfunction later in life.

    1. Neuroscience
    Sven Ohl, Martin Rolfs
    Research Article

    Detecting causal relations structures our perception of events in the world. Here, we determined for visual interactions whether generalized (i.e. feature-invariant) or specialized (i.e. feature-selective) visual routines underlie the perception of causality. To this end, we applied a visual adaptation protocol to assess the adaptability of specific features in classical launching events of simple geometric shapes. We asked observers to report whether they observed a launch or a pass in ambiguous test events (i.e. the overlap between two discs varied from trial to trial). After prolonged exposure to causal launch events (the adaptor) defined by a particular set of features (i.e. a particular motion direction, motion speed, or feature conjunction), observers were less likely to see causal launches in subsequent ambiguous test events than before adaptation. Crucially, adaptation was contingent on the causal impression in launches as demonstrated by a lack of adaptation in non-causal control events. We assessed whether this negative aftereffect transfers to test events with a new set of feature values that were not presented during adaptation. Processing in specialized (as opposed to generalized) visual routines predicts that the transfer of visual adaptation depends on the feature similarity of the adaptor and the test event. We show that the negative aftereffects do not transfer to unadapted launch directions but do transfer to launch events of different speeds. Finally, we used colored discs to assign distinct feature-based identities to the launching and the launched stimulus. We found that the adaptation transferred across colors if the test event had the same motion direction as the adaptor. In summary, visual adaptation allowed us to carve out a visual feature space underlying the perception of causality and revealed specialized visual routines that are tuned to a launch’s motion direction.