Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
2.
Nat Commun ; 12(1): 4767, 2021 08 06.
Article in English | MEDLINE | ID: mdl-34362912

ABSTRACT

Axons in the cerebral cortex show a broad range of myelin coverage. Oligodendrocytes establish this pattern by selecting a cohort of axons for myelination; however, the distribution of myelin on distinct neurons and extent of internode replacement after demyelination remain to be defined. Here we show that myelination patterns of seven distinct neuron subtypes in somatosensory cortex are influenced by both axon diameter and neuronal identity. Preference for myelination of parvalbumin interneurons was preserved between cortical areas with varying myelin density, suggesting that regional differences in myelin abundance arises through local control of oligodendrogenesis. By imaging loss and regeneration of myelin sheaths in vivo we show that myelin distribution on individual axons was altered but overall myelin content on distinct neuron subtypes was restored. Our findings suggest that local changes in myelination are tolerated, allowing regenerated oligodendrocytes to restore myelin content on distinct neurons through opportunistic selection of axons.


Subject(s)
Brain/physiology , Cerebral Cortex/physiology , Myelin Sheath/physiology , Neurons/physiology , Regeneration/physiology , Animals , Axons/physiology , Female , Interneurons/physiology , Male , Mice , Oligodendroglia , Organogenesis/physiology , Parvalbumins , Somatosensory Cortex
3.
Front Cell Neurosci ; 15: 667595, 2021.
Article in English | MEDLINE | ID: mdl-33912017

ABSTRACT

Oligodendrocytes exert a profound influence on neural circuits by accelerating action potential conduction, altering excitability, and providing metabolic support. As oligodendrogenesis continues in the adult brain and is essential for myelin repair, uncovering the factors that control their dynamics is necessary to understand the consequences of adaptive myelination and develop new strategies to enhance remyelination in diseases such as multiple sclerosis. Unfortunately, few methods exist for analysis of oligodendrocyte dynamics, and even fewer are suitable for in vivo investigation. Here, we describe the development of a fully automated cell tracking pipeline using convolutional neural networks (Oligo-Track) that provides rapid volumetric segmentation and tracking of thousands of cells over weeks in vivo. This system reliably replicated human analysis, outperformed traditional analytic approaches, and extracted injury and repair dynamics at multiple cortical depths, establishing that oligodendrogenesis after cuprizone-mediated demyelination is suppressed in deeper cortical layers. Volumetric data provided by this analysis revealed that oligodendrocyte soma size progressively decreases after their generation, and declines further prior to death, providing a means to predict cell age and eventual cell death from individual time points. This new CNN-based analysis pipeline offers a rapid, robust method to quantitatively analyze oligodendrocyte dynamics in vivo, which will aid in understanding how changes in these myelinating cells influence circuit function and recovery from injury and disease.

4.
Elife ; 92020 05 27.
Article in English | MEDLINE | ID: mdl-32459173

ABSTRACT

Destruction of oligodendrocytes and myelin sheaths in cortical gray matter profoundly alters neural activity and is associated with cognitive disability in multiple sclerosis (MS). Myelin can be restored by regenerating oligodendrocytes from resident progenitors; however, it is not known whether regeneration restores the complex myelination patterns in cortical circuits. Here, we performed time lapse in vivo two photon imaging in somatosensory cortex of adult mice to define the kinetics and specificity of myelin regeneration after acute oligodendrocyte ablation. These longitudinal studies revealed that the pattern of myelination in cortex changed dramatically after regeneration, as new oligodendrocytes were formed in different locations and new sheaths were often established along axon segments previously lacking myelin. Despite the dramatic increase in axonal territory available, oligodendrogenesis was persistently impaired in deeper cortical layers that experienced higher gliosis. Repeated reorganization of myelin patterns in MS may alter circuit function and contribute to cognitive decline.


Subject(s)
Myelin Sheath/metabolism , Somatosensory Cortex/metabolism , Animals , Axons/chemistry , Axons/metabolism , Female , Humans , Kinetics , Male , Mice , Mice, Inbred C57BL , Multiple Sclerosis/metabolism , Myelin Sheath/chemistry , Oligodendroglia/chemistry , Oligodendroglia/metabolism , Remyelination , Somatosensory Cortex/chemistry
SELECTION OF CITATIONS
SEARCH DETAIL
...