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Microglia phagocytose myelin sheaths to modify developmental myelination
Alexandria N Hughes1, Bruce Appel2
1Neuroscience Graduate Program, University of Colorado, Aurora, CO, USA.
Abstract:
During development, oligodendrocytes contact and wrap neuronal axons with myelin. Similarly to neurons and synapses, excess myelin sheaths are produced and selectively eliminated, but how elimination occurs is unknown. Microglia, the resident immune cells of the central nervous system, engulf surplus neurons and synapses. To determine whether microglia also prune myelin sheaths, we used zebrafish to visualize and manipulate interactions between microglia, oligodendrocytes, and neurons during development. We found that microglia closely associate with oligodendrocytes and specifically phagocytose myelin sheaths. By using a combination of optical, genetic, chemogenetic, and behavioral approaches, we reveal that neuronal activity bidirectionally balances microglial association with neuronal cell bodies and myelin phagocytosis in the optic tectum. Furthermore, multiple strategies to deplete microglia resulted in oligodendrocytes maintaining excessive and ectopic myelin. Our work reveals a neuronal activity-regulated role for microglia in modifying developmental myelin targeting by oligodendrocytes.
Insights
Microglia, the brain's immune cells, prune excess myelin sheaths during development. Neuronal activity regulates this myelin pruning by microglia, ensuring proper myelination.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Oligodendrocytes myelinate neuronal axons during development.
- Excess myelin is produced and eliminated, but the mechanism of myelin elimination is unknown.
- Microglia are known to engulf surplus neurons and synapses.
Purpose of the Study:
- To investigate whether microglia prune myelin sheaths.
- To understand the role of neuronal activity in myelin pruning.
- To determine the consequences of microglial depletion on myelin development.
Main Methods:
- In vivo imaging in zebrafish to visualize microglia-oligodendrocyte-neuron interactions.
- Genetic and chemogenetic manipulation of microglia and neuronal activity.
- Behavioral analysis to assess functional outcomes.
Main Results:
- Microglia were observed to closely associate with oligodendrocytes and phagocytose myelin sheaths.
- Neuronal activity was found to bidirectionally regulate microglial association with neurons and myelin phagocytosis in the optic tectum.
- Microglia depletion led to excessive and ectopic myelin formation.
Conclusions:
- Microglia play a crucial role in pruning excess myelin sheaths during development.
- Neuronal activity regulates microglial myelin pruning, impacting oligodendrocyte targeting.
- This study reveals a novel function for microglia in regulating myelin homeostasis.
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