Neuroscientists have known since the 1960s what nerves tell a person’s legs to step off the curb to cross the street. But until now, they had no idea which hold the person back to avoid getting hit by a car.
By stimulating nerve cells with light, a group of neuroscientists at the Karolinska Institut in Stockholm both defined the aptly named “stop neurons” and saw how they work in walking mice. The team used a “bottom-up approach” to explore how the spinal cord, lower in the chain of neural command, communicates with the brain stem, which is higher in the chain.
Nerve cells that give rise to other functions we do not consciously think about, like breathing and keeping balance, are located in same area—effectively, as coauthor Ole Kiehn puts it, “one big mess of integrated networks.”
To find the stop neurons, Kiehn and Julien Bouvier first modified a mouse’s brain stem to be sensitive to light stimulation, then sliced it into smaller and smaller segments. They removed parts until light no longer stimulated the segment. From this, the researchers pinpointed a cluster of “stop neurons” that extend down part of the spinal cord that, when stimulated tell the spinal cord to halt locomotion.
What particularly surprised Bouvier was that “those stop cells are excitatory.” In order to stop motion, the cells need to be stimulated. It’s not enough to simply interrupt the locomotion signal.
Bouvier compares it to driving a car. As long as you press the gas pedal, your car will move forward. Going into the study, scientists thought that releasing the pedal would eventually stop the car, or gradually mute the instructions to keep walking. ”But what we found was a brake pedal used only to stop,” Bouvier said.
Watching the pathway unfold in mice supported their earlier findings. When the researchers pulsed light on stop neurons, the mice came to a stop. Light did not have an effect on mice that had blocked stop neurons—instead of stopping, they kept walking.
Interestingly, the mice that could stop did so smoothly. They finished the step they were about to do. This behavior is very different from freezing, an all-over muscle contraction in response to fear. Bouvier said the smooth stopping allows animals to “keep posture,” making them less likely to fall or lose balance.
The study, published in the November issue of Cell, is a step toward understanding how the body controls marching orders at the neural level and beyond the muscular level. Thomas Knopfel, a professor of neuroscience at Imperial College London, thinks Bouvier’s study “might be a step forward with medical problems associated with the brain and spinal cord.”
Leg paralysis from a damaged nerve can disrupt communication between the brain and spinal cord. Knopfel speculated that an implantable device could be connected to this injured nerve, which could help patch this faulty circuit and help a patient learn to move his or her leg again. The same technology the researchers at Karolinska used—called optogenetics—could be used to make this device.
Kiehn speculated that stop neuron activity might contribute to motor symptoms of Parkinson’s disease. One common symptom of late stage Parkinson’s is an involuntary “freezing gait.” Kiehn thinks this could be a sign that the locomotion “start signal” does not work properly, or that stop neurons may be less active than normal. Future tests will involve trying to identify these neurons in diseased mice.
Bouvier has further questions in further exploring stop neurons and understanding how the spinal cord is controlled by brain stem. Among them: Are these neurons a “general brake for all behaviors?”
We may not consciously think about every time we start and stop to walk, but locomotion is the output of many brain activities. Stop neurons are a critical link in this chain of command; they are the neural brake pedal that saves us from cars having to slam theirs’ in the crosswalk. “Even though movement may sound like a boring, noncognitive behavior, it is really one of the most important behaviors,” Kiehn said.