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Increase of vesicular glutamate transporter 2 co-expression in the deep cerebellar nuclei related to skilled reach learning
Department of Rehabilitation Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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). Instituto de Tecnologías Biomédicas, Departamento de Ciencias Médicas Básicas, Universidad de La Laguna, Tenerife, Spain.ORCID-id: 0000-0002-3706-1320
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).ORCID-id: 0000-0002-4618-7267
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2022 (Engelska)Ingår i: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1782, artikel-id 147842Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Motor learning induces plasticity in multiple brain regions involving the cerebellum as a crucial player. Synaptic plasticity in the excitatory collaterals to the cerebellar output, the deep cerebellar nuclei (DCN), have recently been shown to be an important part of motor learning. These synapses are composed of climbing fiber (CF) and mossy fiber synapses, with the former conveying unconditioned and the latter conditioned responses in classical conditioning paradigms. The CF synapse on to the cerebellar cortex and the DCN express vesicular transporter 2 (vGluT2), whereas mossy fibers express vGluT1 and /or vGluT2 in their terminals. However, the underlying regulatory mechanism of vGluT expression in the DCN remains unknown. Here we confirm the increase of vGluT2 in a specific part of the DCN during the acquisition of a skilled reaching task in mice. Furthermore, our findings show that this is due to an increase in co-expression of vGluT2 in vGluT1 presynapses instead of the formation of new vGluT2 synapses. Our data indicate that remodeling of synapses – in contrast to synaptogenesis - also plays an important role in motor learning and may explain the presence of both vGluT's in some mossy fiber synapses.

Ort, förlag, år, upplaga, sidor
Elsevier, 2022. Vol. 1782, artikel-id 147842
Nyckelord [en]
3D reconstruction, Cerebellum, Motor learning, Synapse
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
URN: urn:nbn:se:umu:diva-193154DOI: 10.1016/j.brainres.2022.147842ISI: 000792764600002PubMedID: 35192848Scopus ID: 2-s2.0-85126004419OAI: oai:DiVA.org:umu-193154DiVA, id: diva2:1646375
Tillgänglig från: 2022-03-22 Skapad: 2022-03-22 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, TomásEstévez-Silva, HéctorMarcellino, DanielSultan, Fahad

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