| RRC ID |
87412
|
| Author |
Braaker PN, Mi X, Soong D, Bin JM, Marshall-Phelps K, Bradley S, Benito-Kwiecinski S, Meng J, Arafa D, Richmond C, Keatinge M, Yu G, Almeida RG, Lyons DA.
|
| Title |
Activity-driven myelin sheath growth is mediated by mGluR5.
|
| Journal |
Nat Neurosci
|
| 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.
|
| Volume |
28(6)
|
| Pages |
1213-1225
|
| Published |
2025-6-1
|
| DOI |
10.1038/s41593-025-01956-9
|
| PII |
10.1038/s41593-025-01956-9
|
| PMID |
40369366
|
| PMC |
PMC12148935
|
| MeSH |
Animals
Animals, Genetically Modified
Myelin Sheath* / metabolism
Myelin Sheath* / physiology
Neurons / metabolism
Neurons / physiology
Oligodendroglia* / metabolism
Oligodendroglia* / physiology
Optogenetics
Receptor, Metabotropic Glutamate 5* / genetics
Receptor, Metabotropic Glutamate 5* / metabolism
Receptor, Metabotropic Glutamate 5* / physiology
Zebrafish
Zebrafish Proteins* / genetics
Zebrafish Proteins* / metabolism
|
| IF |
20.071
|
| Resource |
| Zebrafish |
Tg(chx10:Gal4) |
