Cough or sneezing? How does the brain know what to give free rein?

Sneezing neurons activated by triggers such as pollen or viral infection send an "achu" signal, while cough neurons cause hacking.

Does the smell of pollen cause sneezing or coughing? Scientists have discovered nerve cells that cause one reaction instead of another: "sneezing neurons" in the nasal passages transmit sneezing signals to the brain, and individual neurons send coughing messages, according to a study1 conducted on mice.

The results can lead to new and improved treatments for diseases such as allergies and chronic cough. This is encouraging news because these conditions can be "incredibly disappointing" and the side effects of current treatments can be "incredibly problematic," says pulmonologist Matthew Drake of the Oregon Health and Science University in Portland, who was not involved in the work. The study was published today in Cell.

Signals spewing snot

Previous work2 classified mouse respiratory neurons based on protein complexes called ion channels, which are transmitted on the surface of cells.

To find out which nasal neurons cause sneezing, the researchers exposed mice to various compounds, each of which is known to activate certain types of ion channels.

They succeeded when a substance called BAM 8-22 made the mice sneeze. It is known that this compound activates an ion channel called MrgprC11, which makes researchers suspect that neurons carrying MrgprC11 cause sneezing. Indeed, when the researchers removed MrgprC11 from the alleged sneezing neurons and then infected the mice with the flu, they found sick, but not sneezing mice.

Even though sneezing neurons were excluded from the field of vision, sick mice continued to experience cap-like reactions to influenza infection. Using methods similar to those aimed at sneezing neurons, the researchers tracked the cough reaction to a set of neurons in the trachea that express a signaling chemical called somatostatin.

Viruses "evolve very quickly," says neuroscientist and co-author of the study Qin Liu from the University of Washington in St. Louis, Missouri. This could explain why there are two separate systems capable of detecting and removing them from the respiratory tract.

Now Liu and her colleagues want to find out what happens after the sneezing and cough neurons work and send a signal to the brain. She believes that it is likely that their signals are transmitted to the brain's respiratory control center, where they change the nature of breathing, causing either coughing or sneezing.

Other achu neurons?

The next serious task is to find out if similar sets of neurons exist in humans, says neurobiologist Patrick Earnforce from the Karolinska Institute in Stockholm. According to Liu, preliminary data indicate that yes, but additional research is needed.

Some researchers suspect that new neurons responsible for sneezing and coughing have yet to be found. According to sensory neurobiologist Stephen Liberles from Harvard Medical School in Boston, Massachusetts, most reactions to sensory information are caused by numerous categories of neurons, and sneezing and coughing are likely to be similar.

According to Drake, coughing can be so constant that people lose consciousness. And yet doctors do not have good options for cough treatment. Opiates, such as codeine, are the most effective drugs available, but they can cause severe drowsiness and addiction.

The lack of effective drugs may lead to doctors abandoning cough treatment, says Drake. "I hope that the appearance of new treatments on the market will really change our idea of how to treat cough and our enthusiasm for its treatment," he says.