Neurotransmitter-activated GPCR signaling in myelin plasticity

Myelination is increasingly recognized as a dynamic and adaptive process regulated by oligodendrocytes throughout life. Beyond providing electrical insulation, myelin supports axonal metabolism and may serve as an energy reservoir under metabolic stress, highlighting the importance of physiological myelin turnover. Dysregulation of myelin dynamics contributes to a wide spectrum of neurological disorders, including demyelinating, neurodegenerative, and neuropsychiatric diseases. Growing evidence indicates that neurotransmitter signaling through G protein-coupled receptors (GPCRs) expressed by oligodendrocyte lineage cells regulates myelin formation, remodeling, and repair. In this review, we discuss how neurotransmitter-activated GPCRs control oligodendrocyte function and myelin plasticity, and we explore their potential as targets to promote myelin regeneration and restore neural circuit function.