by a mouse running on a treadmill embedded in the virtual reality corridor. In his mind, he sees himself speeding down a tunnel with a clear pattern of light in front of him. Through training, the mouse has learned that if he stops at the lights and stays in this position for 1.5 seconds, he will receive a reward – a small glass of water. Then he can run to another cluster of lights to get another reward.
This setup is the basis for research published in July. Cell Reports By neuroscientists Elie Adam, Taylor Johns, and Mriganka Sur of the Massachusetts Institute of Technology. It explores a simple question: How does the brain in mice, humans, and other mammals work so fast that it stops us instantly? The new study reveals that the brain isn’t wired to deliver a sharp “stop” command in the most direct or intuitive way. Instead, it uses a more complex signaling system based on computational principles. This arrangement may sound overly complex, but it’s a surprisingly clever way to control behavior where commands from the brain need to be more precise than they could be.
The control over the simple mechanics of walking or running is fairly easy to describe: The mesencephalic locomotor region (MLR) of the brain sends signals to neurons in the spinal cord, which send inhibitory or excitatory impulses to the motor neurons that govern the leg muscles: Stop. To go. Stop. To go. Each signal is a surge of electrical activity produced by clusters of neurons firing.
However, the story gets more complicated when goals arise, such as a tennis player wanting to run to a certain spot on the court or a thirsty mouse seeing an exhilarating reward from afar. Biologists have long understood that targets are formed in the cerebral cortex of the brain. How does the brain turn a target (stop running there for a reward) into a precisely timed signal that tells the MLR to hit the brakes?
“Humans and mammals have extraordinary abilities when it comes to sensory-motor control,” said Sridevi Sarma, a neuroscientist at Johns Hopkins University. “For decades, people have been investigating what is in our brains that makes us so agile, fast and robust.”
Fastest and Furry
To understand the answer, the researchers calculated how long it took for the animal to slow down from top speed to full stop, while monitoring the neural activity in a mouse’s brain. They hoped to see an inhibitory signal surge to the MLR that triggers an almost instantaneous stop of the legs, like an electric switch that turns off a light bulb.
But a discrepancy in the data quickly undermined that theory. They observed a “stop” signal flowing into the MLR as the mouse slowed down, but the intensity did not increase fast enough to explain how fast the animal stopped.
“If you take the stop signals and send them to the MLR, the animal will stop, but the math tells us it won’t be fast enough to stop,” Adam said.
“The cortex doesn’t provide a key,” Sur said. “We thought the cortex would do that, going from 0 to 1 with a fast signal. It doesn’t do that, that’s the puzzle.
So the researchers knew there had to be an additional signaling system at work.
To find it, they looked again at the anatomy of the mouse brain. Between the cortex where targets arise and the MLR, which controls movement, is another region, the subthalamic nucleus (STN). It was already known that the STN binds to the MLR in two ways: One sends excitatory signals and the other sends inhibitory signals. The researchers noticed that the MLR responded to the interaction between the two signals rather than relying on the strength of one.
