Activity-driven myelin sheath growth is mediated by mGluR5.

Area of Science:

• Neuroscience
• Cell Biology
• Developmental Biology

Background:

• Neuronal activity influences myelination by oligodendrocytes in the central nervous system.
• The precise molecular mechanisms linking neuronal activity to myelination remain largely unknown.

Purpose of the Study:

• To investigate the molecular mechanisms of activity-regulated myelination in vivo.
• To identify key molecular players mediating the influence of neuronal activity on oligodendrocyte myelination.

Main Methods:

• Utilized zebrafish as an in vivo model system.
• Employed pharmacological manipulation, genetic approaches, functional imaging, and optogenetic stimulation.
• Assessed myelin sheath elongation and oligodendrocyte lineage development.

Main Results:

• Metabotropic glutamate receptor 5 (mGluR5) inhibition impaired, while activation promoted, myelin sheath elongation.
• mGluR5 loss-of-function mutants showed impaired myelin growth; oligodendrocyte-specific mGluR5 gain of function enhanced sheath elongation.
• mGluR5 was identified as the mediator of activity-driven calcium transients in myelin and activity-dependent myelin elongation.

Conclusions:

• Metabotropic glutamate receptor 5 (mGluR5) is a critical mediator of neuronal activity's influence on myelination by oligodendrocytes.
• These findings highlight mGluR5's role in activity-dependent myelination, suggesting potential therapeutic targets for neurological disorders.