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Learning-related contraction of gray matter in rodent sensorimotor cortex is associated with adaptive myelination
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).ORCID-id: 0000-0002-5589-9864
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).ORCID-id: 0000-0002-3706-1320
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
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2022 (Engelska)Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 11, artikel-id e77432Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

From observations in rodents, it has been suggested that the cellular basis of learning-dependent changes, detected using structural 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 nonlinear decreases in gray matter volume (GMV) juxtaposed to nonlinear increases in white matter volume (WMV) within GM that were best modeled by an asymptotic time course. Using an atlas-based cortical mask, we found nonlinear 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 nonlinear 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 nonlinear increase of intracortical myelin during learning and support the hypothesis that myelin is a component of structural changes observed by VBM during learning.

Ort, förlag, år, upplaga, sidor
eLife Sciences Publications , 2022. Vol. 11, artikel-id e77432
Nyckelord [en]
motor skill learning, mouse, MRI, myelin, neuroscience, VBM
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
URN: urn:nbn:se:umu:diva-201415DOI: 10.7554/eLife.77432ISI: 000890954100001PubMedID: 36350292Scopus ID: 2-s2.0-85142401457OAI: oai:DiVA.org:umu-201415DiVA, id: diva2:1715198
Forskningsfinansiär
Kempestiftelserna, JCK-1922.2Magnus Bergvalls Stiftelse, 2016-01639Vetenskapsrådet, 2015-01717Vetenskapsrådet, 2018-01047Tillgänglig från: 2022-12-01 Skapad: 2022-12-01 Senast uppdaterad: 2023-09-05Bibliografiskt granskad
Ingår i avhandling
1. Temporal dynamics of brain plasticity: characterizing brain structural changes during skill acquisition
Öppna denna publikation i ny flik eller fönster >>Temporal dynamics of brain plasticity: characterizing brain structural changes during skill acquisition
2023 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Alternativ titel[sv]
Temporal dynamik av hjärnans plasticitet : karakterisering av strukturella förändringar i hjärnan under inlärning
Abstract [en]

Traditionally, structural plasticity in the human brain has been considered to follow a linear or asymptotic increase over the course of training. However, recent studies using structural MRI revealed transient increases in grey matter volume (GMV) with learning. Furthermore, significant increases in white matter microstructure have been observed in white matter underlying motor cortex in animals at the last training day. Nevertheless, the involvement of activity-dependent myelination has received little attention and the dynamics of myelin plasticity and how it relates to morphometric-based measurements of structural plasticity remains unknown.

In this thesis, to characterize the dynamics of learning-related structural changes in the mouse brain, we have combined a motor skilled learning paradigm with longitudinal in vivo magnetic resonance imaging and immunohistochemical investigation. Wholebrain voxel-based morphometry (VBM) analysis revealed non-linear decreases in GMV juxtaposed with non-linear increases in white matter volume (WMV) in both cortical and subcortical areas of the brain. Analysis of cross-sectional myelin immunoreactivity in forelimb somatosensory cortex confirmed a transient increase in myelin immunoreactivity. Further investigation using confocal microscopy confirmed these changes, specifically to the length density of myelinated axons. The absence of significant histological changes in cortical thickness suggests that nonlinear morphometric changes are likely due to changes in intracortical myelin for which morphometric WMV in somatosensory cortex significantly correlated with myelin immunoreactivity.

Whole-brain VBM revealed non-linear decreases in GMV with learning in primary motor cortex (MOp), secondary motor cortex (MOs) and posterior parietal cortex (PTLp). These areas of the brain are known to be involved in sensory discrimination and motor selection. Using cross-sectional correlational tractography we found an increase in fractional anisotropy (FA) values with learning between MOs and MOp, PTLp and MOs and PTLp and MOp. Increases in FA values suggest an increase in connectivity, which can be attributed to an increase in axon density or myelination. Based on existent literature and our non-linear VBM changes with learning in the deep cerebellar nuclei we investigated synaptic plasticity using immunohistochemical examination of glutamate transporters. We found an increase of vesicular glutamate transporter 2 in pre-existing vesicular glutamate 1 synapses. Our data indicate that remodeling of synapses - in contrast to synaptogenesis – plays an important role in motor learning.

Altogether, these results highlight the importance of non-linear structural plasticity in the acquisition of dexterous motor skill and stress the relevance of adaptive myelination in learning.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå University, 2023. s. 77
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 2253
Nyckelord
Motor learning, brain plasticity, structural plasticity, magnetic resonance imaging, voxel-based morphometry, tractography, connectivity, motor cortex, posterior parietal cortex, cerebellum, vesicular glutamate transporter
Nationell ämneskategori
Medicinska och farmaceutiska grundvetenskaper
Identifikatorer
urn:nbn:se:umu:diva-212932 (URN)978-91-8070-113-6 (ISBN)978-91-8070-112-9 (ISBN)
Disputation
2023-09-08, Auditorium NAT. D.320, Umeå, 13:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2023-08-18 Skapad: 2023-08-16 Senast uppdaterad: 2023-08-18Bibliografiskt granskad

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Mediavilla, TomásÖzalay, ÖzgunEstévez-Silva, Héctor M.Frias, BarbaraOrädd, GregerSultan, Fahad R.Marcellino, Daniel J.

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Mediavilla, TomásÖzalay, ÖzgunEstévez-Silva, Héctor M.Frias, BarbaraOrädd, GregerSultan, Fahad R.Marcellino, Daniel J.
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