Periods of synchronized myelin changes shape brain function and plasticity

Faria, Omar de; Pivoňková, Helena; Varga, Balázs; Timmler, Sebastian; Evans, Kimberley Anne; Káradóttir, Ragnhildur Thóra

doi:10.1038/s41593-021-00917-2

Cited by 92 publications

(92 citation statements)

References 143 publications

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“…In addition, this separation arose from increasing differences in the connectivities of the two subregions with age and may begin as early as post-adolescence or even earlier in early-adolescence but does not show up until young adulthood in the form of a parcellation pattern. Interestingly, previous research indicated that the medial PFC actively enters a prolonged myelination cycle at the time of adolescence, during which it increases in plasticity and, thus, reflects adaptations to the ever-changing environment 70 . By impacting the structural connections, this myelination cycle may be the essential trigger for the developing arealization pattern.…”

Section: Discussionmentioning

confidence: 99%

Anatomical connectivity profile development constrains medial-lateral topography in the dorsal prefrontal cortex

Wen

Shi

Wang

et al. 2022

Preprint

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The prefrontal cortex (PFC) is a highly variable, evolutionarily expanded brain region that is engaged in multiple cognitive processes. The subregions of the PFC mature relatively late compared with other brain regions, and the maturation times vary between these subregions. Among these, the dorsomedial and dorsolateral prefrontal cortex (dmPFC and dlPFC) share a parallel topographic pattern of functional connectivity, while participating in different types of complex behaviors. However, the developmental trajectories of the two areas remain obscure. In this study, we uncovered differences in the developmental trends of the dmPFC and dlPFC. These differences were mainly caused by structural and functional changes in the medial area of the superior frontal gyrus (SFG). The developmentally different arealization patterns were verified using multiple parcellation approaches with multimodal data, including structural magnetic resonance imaging (sMRI), diffusion MRI (dMRI), resting state functional MRI (rfMRI), and a publicly available transcriptomic dataset. Human brain gene expression data was also used to perform downstream analyses, which could inform us about the potential biological mechanisms underlying the developmentally different arealizations. Furthermore, behavioral analyses hinted at the effects of regionalization on ontogeny. In brief, this study revealed a tendency toward a medial-lateral prefrontal division and can provide a fuller understanding of the potential underlying genetic underpinnings as well as of the potential effects on developmental behavior.

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Section: Discussionmentioning

confidence: 99%

Anatomical connectivity profile development constrains medial-lateral topography in the dorsal prefrontal cortex

Wen

Shi

Wang

et al. 2022

Preprint

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“…A carbon dating study of human genomic DNA also showed low levels of oligodendrogenesis in adulthood, which provides further support for the extreme rarity of transient cells in adult human brain 42 . Despite being rare, COPs are a critical cell type for future studies to examine since oligodendrocyte maturation is altered in both neurological diseases 35,43 and human evolution 44,45 . Thus, we underscore the importance of ambient RNA removal, especially for accurate analysis of underrepresented cell types, and here provide novel markers for COPs in the adult human brain.…”

Section: Discussionmentioning

confidence: 99%

Ambient RNA analysis reveals misinterpreted and masked cell types in brain single-nuclei datasets

Caglayan

Liu

Konopka

2022

Preprint

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Ambient RNA contamination in single-cell RNA sequencing (RNA-seq) is a significant problem, but its consequences are poorly understood. Here, we show that ambient RNAs in brain single-nuclei RNA-seq can have a nuclear or extra-nuclear origin with distinct gene set signatures. Both ambient RNA signatures are predominantly neuronal and we find that some previously annotated neuronal cell types are distinguished by ambient RNA. Strikingly, we also detect pervasive neuronal ambient RNA contamination in all glial cell types unless glia and neurons are physically separated prior to sequencing. We demonstrate that this contamination can be removed in silico. We also show that previous annotations of immature oligodendrocytes are likely glial cells contaminated with ambient RNAs. After ambient RNA removal, we detect extremely rare, committed oligodendrocyte progenitor cells, which were infrequently annotated in previous adult human brain datasets. Together, these results provide an in-depth analysis of ambient RNA contamination in brain single-cell datasets.

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“…Although a large proportion of OLs are generated early in postnatal development, OL generation continues into adulthood from abundant OL progenitor cells (OPCs) ( Dawson et al, 2003 ; Rivers et al, 2008 ; Kang et al, 2010 ; Zhu et al, 2011 ; Young et al, 2013 ). Both oligodendrogenesis and myelination at later ages are dynamic processes, likely regulated by diverse mechanisms related to experience and neuronal activity ( Gibson et al, 2014 ; Hughes et al, 2018 ; Mitew et al, 2018 ; de Faria et al, 2021 ). Interestingly, recent evidence suggests that juvenile or adult oligodendrogenesis and subsequent new myelination are required for complex motor learning ( McKenzie et al, 2014 ), memory consolidation ( Steadman et al, 2020 ), and the establishment of proper social behavior ( Makinodan et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Age and Alzheimer’s Disease-Related Oligodendrocyte Changes in Hippocampal Subregions

DeFlitch

González-Fernández

Crawley

et al. 2022

Front. Cell. Neurosci.

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Oligodendrocytes (OLs) form myelin sheaths and provide metabolic support to axons in the CNS. Although most OLs develop during early postnatal life, OL generation continues in adulthood, and this late oligodendrogenesis may contribute to neuronal network plasticity in the adult brain. We used genetic tools for OL labeling and fate tracing of OL progenitors (OPCs), thereby determining OL population growth in hippocampal subregions with normal aging. OL numbers increased up to at least 1 year of age, but the rates and degrees of this OL change differed among hippocampal subregions. In particular, adult oligodendrogenesis was most prominent in the CA3 and CA4 subregions. In Alzheimer’s disease-like conditions, OL loss was also most severe in the CA3 and CA4 of APP/PS1 mice, although the disease did not impair the rate of OPC differentiation into OLs in those regions. Such region-specific, dynamic OL changes were not correlated with those of OPCs or astrocytes, or the regional distribution of Aβ deposits. Our findings suggest subregion-dependent mechanisms for myelin plasticity and disease-associated OL vulnerability in the adult hippocampus.

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Periods of synchronized myelin changes shape brain function and plasticity

Cited by 92 publications

References 143 publications

Anatomical connectivity profile development constrains medial-lateral topography in the dorsal prefrontal cortex

Anatomical connectivity profile development constrains medial-lateral topography in the dorsal prefrontal cortex

Ambient RNA analysis reveals misinterpreted and masked cell types in brain single-nuclei datasets

Age and Alzheimer’s Disease-Related Oligodendrocyte Changes in Hippocampal Subregions

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