Brain nerve fibers interconnect myriad nerve cells and are coated with a fatty insulation to transmit electrical signals at lightning speed. The nerve-coating cells, known as oligodendrocytes, are also critical for powering the brain’s electrical cables on demand through a signaling process regulated by potassium, as discovered by a team of UZH researchers led by Aiman Saab.
Our cognitive and physical abilities rely on electrical signals transmitted through nerve fibers, or axons, across the nervous system. Damage to these axons can disrupt this signal flow and impair brain functions. Signal speed along axons is dramatically enhanced by myelin, a fatty insulation made by oligodendrocytes. Beyond insulation, oligodendrocytes are critically involved in maintaining axonal integrity and brain health.
Zoe Looser and colleagues studied how oligodendrocytes detect and respond to acute changes in axonal activity. Using electrophysiology and biosensor imaging of the optic nerve in mice, they observed that oligodendrocytes sense axonal firing and rapidly increase their glucose consumption to supply axons with the glycolytic product lactate. This process is regulated by potassium signaling and a potassium channel called Kir4.1. Inactivating this channel specifically in oligodendrocytes impaired axonal energy metabolism, including the uptake and consumption of glucose in axons, which led to axonal damage later with age.
The study emphasizes the pivotal role of oligodendrocytes in sustaining axonal metabolism and long-term health. Understanding how oligodendrocytes support axonal health sheds light on the processes contributing to axonal damage in aging and diseases like multiple sclerosis and Alzheimer’s.
Zoe J. Looser, et. al. Oligodendrocyte-axon metabolic coupling is mediated by extracellular K+ and maintains axonal health. Nature Neuroscience (2024). DOI: 10.1038/s41593-023-01558-3
Additional information: Neurohomeostasis and Axon-Glia Research group
Image: Zoe Looser and Aiman Saab
Two-photon microscopy reveals a depth-colored view of oligodendrocytes equipped with a calcium biosensor in an acute optic nerve preparation from a mouse. This technique provides insights into how these cells detect and respond to spikes in nerve fiber activity.