How neurons say ‘go, mouse, go!’

CORNELL (US) — A group of spinal cord nerve cells manages running in mice, telling them when to go—and when to go faster.

To learn more about locomotion in animals, researchers created a wiring diagram of locomotor networks in the spinal cord. In most animals, walking and running share common but overlapping processes.

Locomotion is controlled by a group of neurons called a “central pattern generator” (CPG). When the brain prompts movement, a sort of biological computer program fires motor neurons in the right sequence and intensity to put one foot in front of the other. To move faster, different neurons join in.

The research is published in the journal Nature Communications.

To overcome the challenges of observing neural activity in the mouse spinal cord, researchers inserted microscopic electrodes into single nerve cells and electrically stimulated nerves to simulate signals from the brain. They discovered a group of neurons called interneurons that fired only when signals from the brain called for higher speed.

“These neurons don’t play much of a role in moving slowly,” says Ronald Harris-Warrick, professor of neurobiology at Cornell University. “For that there are others we haven’t discovered yet.”

Normal mice running on a treadmill simply speed up their left-right motion to go faster. University of Chicago researchers recently created genetically modified mice that switch at higher speeds from left-right running to bounding, with the two front legs and two rear legs moving in synchrony.

That’s what most four-legged animals do, Harris-Warrick notes, but for a small creature being chased by a lot of predators, evolution favors left-right running.

“Galloping is faster,” he explains, “but if you’re galloping, it’s hard to turn on a dime. You trade speed for dexterity.”

The high-speed neurons apparently activate a neuronal pathway that inhibits the bounding behavior. Researchers found they could trigger the bounding gait by infusing the nerves with strychnine, which has the same inhibitory effect.

“What this shows us is that the wiring is all there for a mouse to gallop, but these neurons are preventing the animal from galloping,” Harris-Warrick says.

The two-phase approach to locomotion goes back much further in the evolutionary tree. In zebrafish, the activity of interneurons associated with higher swimming speeds is accompanied by weakening or silencing of other interneurons that were active at lower speeds. The high-speed system in zebrafish changes the way the fish makes sharp “escape turns.”

This is the first research to examine the mouse spinal cord at more than a single locomotion speed. Up next will be studies with wider range of speeds that may reveal more variations in the way neurons activate.

The research was supported by the National Institutes of Health (NIH) and the National Science Foundation. The overall locomotion research program is funded by NIH and the Christopher and Dana Reeve Foundation, in the hope that it may eventually lead to better treatment of spinal cord injuries in humans.

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