Axo-vascular coupling mediated by oligodendrocytes

Abstract

AbstractThe high energy requirements of the cortical gray matter are met by the precise cooperation of neurons, glia, and vascular cells in a process known as neurovascular coupling (NVC). In contrast, the existence and significance of NVC in white matter (WM) are still debated and basic regulatory mechanisms are unknown. We recently discovered that oligodendrocytes sense the spiking axons’ activity via NMDA receptors and regulate their cell surface expression of glucose transporter GLUT1 allowing an increase in glycolytic metabolism that enables lactate release to metabolically support the axons. Here, we show for the mouse optic nerve (ON), a model WM tract, that the vascular support is also dynamically controlled. Axonal spiking activity induces small vessel dilations which are sustained for more than 20 minutes upon the ending of electrical stimulation. Pharmacological inhibition shows that the electrically evoked dilation is mediated by the prostaglandin E2 receptor EP4 and can be modulated by the oxygen concentration, as has been shown in the grey matter. Importantly, we found in ONs from conditional mouse mutants that oligodendroglial NMDA receptors are required for this type of neurovascular response, demonstrating a critical role of oligodendrocytes in coupling axonal activity to pericyte function. Reminiscent of NVC in cortical slices, the “axo-vascular” response is slower and may represent a more rudimentary form of neurovascular coupling.