Regulation of lipid synthesis in myelin modulates neural activity and is required for motor learning

Abstract

Brain function relies on both rapid electrical communication in neural circuitry and appropriate patterns or synchrony of neural activity. Rapid communication between neurons is facilitated by wrapping nerve axons with insulation by a myelin sheath composed largely of different lipids. Recent evidence has indicated that the extent of myelination of nerve axons can adapt based on neural activity levels and this adaptive myelination is associated with improved learning of motor tasks, suggesting such plasticity may enhance effective learning. In this study, we examined whether another aspect of myelin plasticity—changes in myelin lipid synthesis and composition—may also be associated with motor learning. We combined a motor learning task in mice with in vivo two‐photon imaging of neural activity in the primary motor cortex (M1) to distinguish early and late stages of learning and then probed levels of some key myelin lipids using mass spectrometry analysis. Sphingomyelin levels were elevated in the early stage of motor learning while galactosylceramide levels were elevated in the middle and late stages of motor learning, and these changes were correlated across individual mice with both learning performance and neural activity changes. Targeted inhibition of oligodendrocyte‐specific galactosyltransferase expression, the enzyme that synthesizes myelin galactosylceramide, impaired motor learning. Our results suggest regulation of myelin lipid composition could be a novel facet of myelin adaptations associated with learning.

Age-related changes after intracerebral hemorrhage: a comparative proteomics analysis of perihematomal tissue

“…Additionally, alterations in the expression of myelin proteins and changes in the regulation of proteins involved in myelination during aging were observed. Myelin plays a crucial role in facilitating efficient nerve signal transmission, and any disturbance of or deterioration in its structure or composition may impact neural communication [ 57 ]. A previous study demonstrated that significant alterations occurred in sphingolipid expression patterns associated with myelin remodeling during the aging process [ 58 ].…”

Activity-dependent oligodendrocyte calcium dynamics and their changes in Alzheimer’s disease

“…Spike signals were filtered within the bandpass of 300 Hz to 8 kHz. Spikes were detected through threshold-level crossing, typically set at 50 μV (Kato et al, 2020(Kato et al, , 2023. Single unit sorting was performed using principal component analysis in an offline sorter (Plexon).…”