Dynamic Energy Supply for Firing Nerve Fibers in the Brain

Brain function depends on the swift movement of electrical signals along axons, the long extensions of nerve cells that connect billions of brain cells. The nerve fibers are insulated by a fatty layer called myelin, which is produced by specialized cells called oligodendrocytes. These cells wrap around and insulate nerve fibers ensuring the rapid and efficient transmission of signals that is essential for brain function.

Oligodendrocytes sense and respond to the electrical signals. “We found that oligodendrocytes not only detect the signals from active nerve fibers, but also respond to them by immediately accelerating their consumption of glucose, a primary energy source,” says Saab. In this way, the oligodendrocytes deliver energy-rich molecules to the rapidly firing axons to support their dynamic energy needs.

To understand how electrically active axons communicate with their surrounding oligodendrocytes, the researchers studied the mouse optic nerve, an ideal pathway for stimulating and monitoring the electrical activity of myelinated axons.

To trigger axonal firing and to observe how oligodendrocytes respond to this activity, they used tiny biosensors: engineered proteins that serve as microscopic detectors of molecular changes. “Using a variety of chemicals and inhibitors, we were able to show that potassium, released by axons during firing, is the key signal that activates the oligodendrocytes,” says Zoe Looser, the first author of the study.

The researchers also identified a specific potassium channel called “Kir4.1” as a key player in the communication between nerve fibers and oligodendrocytes. To study their role, the team used genetically modified mice that lacked these channels in their oligodendrocytes.

In these mice, axons surrounded by oligodendrocytes without these potassium channels showed reduced lactate levels, a key byproduct of glucose metabolism, and a diminished response in lactate surge upon activation. “These changes were associated with reduced glucose metabolism in nerve fibers and ultimately led to severe axon damage as the mice aged,” adds Looser.

Reference: Firing nerve fibers in the brain are supplied with energy on demand; Nature Neuroscience