Cough or sneeze? How the brain knows what to unleash

Does a whiff of pollen trigger a sneeze or a cough? Scientists have discovered nerve cells that cause one response versus another: ‘sneeze neurons’ in the nasal passages relay sneeze signals to the brain, and separate neurons send cough messages, according to a study¹ performed in mice.

The findings could lead to new and improved treatments for conditions such as allergies and chronic coughs. That’s welcome news because these conditions can be “incredibly frustrating” and the side effects of current treatments can be “incredibly problematic”, says pulmonologist Matthew Drake at Oregon Health & Science University in Portland, who was not involved in the work. The study was published today in Cell.

Snot-spewing signals

Previous work² categorized neurons in the mouse airway on the basis of the proteins complexes, called ion channels, that are carried on the cell surfaces.

To work out which nose neurons cause sneezing, researchers exposed mice to various compounds, each known to activate specific types of ion channel.

They struck gold when a substance called BAM 8-22 left the mice sneezing. The compound is known to activate an ion channel called MrgprC11, leading the researchers to suspect that neurons carrying MrgprC11 cause sneezing. Indeed, when the researchers deleted MrgprC11 from the suspected sneeze neurons and then gave mice the flu, they found themselves with sick, but sneezeless, mice.

Even with the sneeze neurons out of the picture, the sick mice continued to have cough-like reactions to influenza infection. Using methods similar to those that homed in on the sneeze neurons, the researchers tracked the cough response to a set of neurons in the trachea that express a signalling chemical called somatostatin.

Viruses “evolve very quickly”, says neuroscientist and study co-author Qin Liu at Washington University in St. Louis, Missouri. That could explain why there are two separate systems capable of detecting and clearing them from the airways.

Now, Liu and her colleagues want to figure out what happens after sneeze and cough neurons are triggered and signal the brain. She thinks it’s likely that their signals travel to the brain’s respiration control centre, where they alter breathing patterns to produce either a cough or a sneeze.

Other achoo neurons?

The next major challenge is to work out whether similar sets of neurons exist in humans, says neuroscientist Patrik Ernfors at the Karolinska Institute in Stockholm. Preliminary evidence suggests that they do, Liu says, but more research is needed.

The push for better flu therapies

Some researchers suspect that more neurons for sneeze and cough are still waiting to be found. Most responses to sensory information are triggered by numerous categories of neuron, and sneezing and coughing are likely to be similar, says sensory neuroscientist Stephen Liberles at Harvard Medical School in Boston, Massachusetts.

Coughing can be so persistent that it causes people to pass out, Drake says. And yet doctors don’t have good options for treating coughs. Opiates such as codeine are the most effective drugs available, but they can make people extremely drowsy and they’re addictive.

This lack of effective medications can lead doctors to give up on alleviating coughs, Drake says. “I’m hopeful that as new therapies enter the market, that’s going to really change our thinking about how to treat [cough] and our enthusiasm for treating it,” he says.