Oligodendrocyte-axon metabolic coupling is mediated by extracellular K + and maintains axonal health.
Zoe J LooserZainab FaikLuca RavottoHenri S ZankerRamona B JungHauke B WernerTorben RuhwedelWiebke MöbiusDwight E BerglesL Felipe BarrosKlaus-Armin NaveBruno WeberAiman S SaabPublished in: Nature neuroscience (2024)
The integrity of myelinated axons relies on homeostatic support from oligodendrocytes (OLs). To determine how OLs detect axonal spiking and how rapid axon-OL metabolic coupling is regulated in the white matter, we studied activity-dependent calcium (Ca 2+ ) and metabolite fluxes in the mouse optic nerve. We show that fast axonal spiking triggers Ca 2+ signaling and glycolysis in OLs. OLs detect axonal activity through increases in extracellular potassium (K + ) concentrations and activation of Kir4.1 channels, thereby regulating metabolite supply to axons. Both pharmacological inhibition and OL-specific inactivation of Kir4.1 reduce the activity-induced axonal lactate surge. Mice lacking oligodendroglial Kir4.1 exhibit lower resting lactate levels and altered glucose metabolism in axons. These early deficits in axonal energy metabolism are associated with late-onset axonopathy. Our findings reveal that OLs detect fast axonal spiking through K + signaling, making acute metabolic coupling possible and adjusting the axon-OL metabolic unit to promote axonal health.
Keyphrases
- optic nerve
- spinal cord injury
- optical coherence tomography
- late onset
- public health
- healthcare
- white matter
- mental health
- traumatic brain injury
- early onset
- room temperature
- liver failure
- multiple sclerosis
- adipose tissue
- type diabetes
- insulin resistance
- human health
- heart rate
- social media
- climate change
- protein kinase
- heart rate variability
- health promotion
- stress induced
- high fat diet induced
- loop mediated isothermal amplification