PUBLICATION
Activity-driven myelin sheath growth is mediated by mGluR5
- Authors
- Braaker, P.N., Mi, X., Soong, D., Bin, J.M., Marshall-Phelps, K., Bradley, S., Benito-Kwiecinski, S., Meng, J., Arafa, D., Richmond, C., Keatinge, M., Yu, G., Almeida, R.G., Lyons, D.A.
- ID
- ZDB-PUB-250515-38
- Date
- 2025
- Source
- Nature Neuroscience : (Journal)
- Registered Authors
- Almeida, Rafael, Lyons, David A., Richmond, Claire
- Keywords
- none
- MeSH Terms
-
- Animals
- Receptor, Metabotropic Glutamate 5*/genetics
- Receptor, Metabotropic Glutamate 5*/metabolism
- Receptor, Metabotropic Glutamate 5*/physiology
- Oligodendroglia*/metabolism
- Oligodendroglia*/physiology
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Myelin Sheath*/metabolism
- Myelin Sheath*/physiology
- Neurons/metabolism
- Neurons/physiology
- Animals, Genetically Modified
- Zebrafish
- Optogenetics
- PubMed
- 40369366 Full text @ Nat. Neurosci.
Citation
Braaker, P.N., Mi, X., Soong, D., Bin, J.M., Marshall-Phelps, K., Bradley, S., Benito-Kwiecinski, S., Meng, J., Arafa, D., Richmond, C., Keatinge, M., Yu, G., Almeida, R.G., Lyons, D.A. (2025) Activity-driven myelin sheath growth is mediated by mGluR5. Nature Neuroscience. :.
Abstract
Myelination by oligodendrocytes in the central nervous system is influenced by neuronal activity, but the molecular mechanisms by which this occurs have remained unclear. Here we employed pharmacological, genetic, functional imaging and optogenetic-stimulation approaches in zebrafish to assess activity-regulated myelination in vivo. Pharmacological inhibition and activation of metabotropic glutamate receptor 5 (mGluR5) impaired and promoted myelin sheath elongation, respectively, during development, without otherwise affecting the oligodendrocyte lineage. Correspondingly, mGluR5 loss-of-function mutants exhibit impaired myelin growth, while oligodendrocyte-specific mGluR5 gain of function promoted sheath elongation. Functional imaging and optogenetic-stimulation studies revealed that mGluR5 mediates activity-driven high-amplitude Ca2+ transients in myelin. Furthermore, we found that long-term stimulation of neuronal activity drives myelin sheath elongation in an mGluR5-dependent manner. Together these data identify mGluR5 as a mediator of the influence of neuronal activity on myelination by oligodendrocytes in vivo, opening up opportunities to assess the functional relevance of activity-regulated myelination.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping