Researchers Have Determined How Mice Cough, and It Matters for Humans

Yawns, sighs, regular breath — all these seemingly automated forms of inhaling and exhaling are coordinated by unique neuronal circuits in the brain that receive signals about the body’s condition and then send signals about how to respond.

A team of scientists from the University of Michigan have now mapped the circuit that controls one often-irritating form of exhaling, the cough, using a model organism that was not previously known to exhibit this behavior.

The findings, featured on the cover of the September 2024 issue of Nature Neuroscience, provide a powerful tool for better understanding and treating excessive coughing in humans. Excessive dry coughing, which does not function to protect the body, is one of the most common medical complaints; and current over-the-counter treatments have been found no more effective than placebos.

Researchers in the lab of neuroscientist Peng Li, Ph.D., at the U-M Life Sciences Institute (LSI) use mice as a model to understand the molecular mechanisms that coordinate different forms of breathing and identify implications for human health and disease. 

By activating different neuronal populations in the region of the mouse brain that controls breathing, they aim to understand how specific groups of neurons produce such widely varying forms of breathing patterns. The team previously found that different neurons are involved in sighs, depending on whether the sigh is in response to an emotion or to low oxygen levels. 

This newest finding arose when they activated a different subset of neurons and noticed an unfamiliar breathing pattern in the animal. 

“We were puzzled with this pattern because we hadn’t noticed it before in our routine recording. We looked into the literature, and we realized it looked exactly like a cough in other species,” explains Li, an assistant professor in the U-M School of Dentistry and Medical School and a research assistant professor at the LSI. “But in the field, people have traditionally thought mice do not actually cough.” 

Through a series of experiments, the team not only demonstrated that the mice were coughing, but also determined that a group of neurons called tachykinin 1 neurons play a central role in the neural circuit responsible for producing this behavior.

While coughs have been studied in a few other species, those mammals are more difficult to investigate at the genetic and molecular level. This new observation in mice opens the door to finding potential drug targets for coughing, due to the advanced genetic tools available for studying this widely used model organism.

“This opens a lot of opportunities across the field,” Li says. “We now have a new model for studying the specific molecular mechanisms underlying coughs and even potentially identifying new targets for developing better anti-coughing treatments.”