Summary: Results from a mouse study identify the specific neurons and peptide that drive the sneeze reflex.
Source: WUSTL
A tickle in the nose triggers sneezing to expel irritants and pathogens, but the cellular and molecular mechanisms behind this reflex extend beyond the sinuses and have been incompletely understood.
Researchers at Washington University School of Medicine in St. Louis have now mapped, in mice, the neurons and neuropeptide that control chemically and allergy-induced sneezing.
“Understanding how neurons respond to allergens and viruses to produce sneezing could point to ways to reduce the spread of respiratory infections,” said Qin Liu, PhD, an associate professor of anesthesiology and the study’s senior author.
These findings were published June 15 in the journal Cell.
Liu, who works at the university’s Center for the Study of Itch and Sensory Disorders, explained that sneezing driven by seasonal allergies and viral infections affects many people, and that dissecting the neural pathways behind symptoms such as itchy eyes and excessive sneezing could aid development of treatments.
Although scientists first located a sneeze-evoking region in the central nervous system more than two decades ago, the specific cells and molecular signals that make the reflex occur were not well defined. Sneezing remains one of the most powerful ways respiratory infections spread because it propels large numbers of droplets into the air.
In this study, Liu and colleagues developed a mouse model to identify which nasal sensory neurons transmit signals that produce sneezes. They exposed mice to aerosolized droplets containing histamine or capsaicin—the spicy component of chili peppers—and both agents reliably induced sneezing, as they do in humans.
Focusing on neurons known to respond to capsaicin, the team identified a population of small-diameter nasal sensory neurons linked specifically to capsaicin-induced sneezing. Screening the molecules these sensory neurons release, they found the neuropeptide neuromedin B (NMB) is essential for signaling the sneeze reflex.
When the researchers selectively removed the neurons in the sneeze-evoking brain region that respond to NMB, mice no longer sneezed in response to the usual triggers. Those postsynaptic neurons express the neuromedin B receptor (NMBR), and mice lacking NMBR showed a marked reduction in sneezing.
“Surprisingly, the sneeze-evoking neurons are located outside the classical brainstem regions known for controlling breathing,” Liu said. “Nonetheless, we found that these sneeze-related neurons are directly connected to respiratory control regions by axonal projections.”
Further experiments showed that applying the NMB peptide to the relevant brain area activated the sneeze reflex even without nasal exposure to capsaicin, histamine, or other allergens. This demonstrates that NMB signaling in the central pathway is sufficient to trigger sneezing.
Because many respiratory pathogens—including many rhinoviruses and coronaviruses such as MERS-CoV and SARS-CoV-2—can spread via aerosolized droplets, the investigators note that targeting NMB or its receptor could be a strategy to reduce transmission by limiting sneezing in infected individuals.
“A single sneeze can produce tens of thousands of droplets that remain airborne for minutes,” Liu said. “By contrast, a cough releases far fewer droplets. If we can identify and block the pathways that cause excessive or pathogen-driven sneezing, it could help prevent outbreaks and treat pathological sneezing caused by allergies.”
Citation: Li F, et al. Sneezing reflex is mediated by a peptidergic pathway from nasal sensory neurons to brainstem respiratory neurons. Cell, published online June 15, 2021.
Funding: This research was funded by the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Eye Institute of the National Institutes of Health (grant numbers R01 AI125743, R01 EY024702, K08 AR065577, R01 AR07116, and R01 AR77007). Additional support came from the Pew Scholar Research Award, the American Skin Association and the Doris Duke Charitable Foundation.
About this neuroscience research news
Source: WUSTL
Contact: Jim Dryden – WUSTL
Image: The image is in the public domain
Original Research: Closed access. “Sneezing reflex is mediated by a peptidergic pathway from nose to brainstem” by Qin Liu et al., Cell.
Abstract
Sneezing reflex is mediated by a peptidergic pathway from nose to brainstem
Highlights
- • Identification of a peptidergic pathway responsible for chemically and allergy-induced sneezing
- • Nasal sensory neurons release neuromedin B (NMB) to transmit sneeze signals
- • NMB activates central NMBR+ neurons in the sneeze-evoking brainstem region
- • NMBR+ neurons project to the caudal ventral respiratory group (cVRG) to drive sneezing
Summary
Sneezing is an important respiratory reflex often associated with allergic rhinitis and viral respiratory infections, yet the neural circuitry underlying it has remained largely unclear. Prior anatomical work located a sneeze-evoking region in the brainstem that corresponds to where nasal sensory neurons terminate, suggesting the reflex depends on a postsynaptic neuronal population in that area.
By screening signaling molecules released by nasal sensory neurons, the study identified neuromedin B (NMB) as a critical neuropeptide for triggering sneezing. Ablation of NMB-sensitive postsynaptic neurons in the sneeze-evoking region, or genetic loss of the NMB receptor, abolished the sneeze reflex in mice.
Importantly, NMB-sensitive neurons send output to the caudal ventral respiratory group (cVRG). Chemical activation of these neurons causes action potentials in cVRG neurons and elicits sneezing behavior, defining a peptidergic nose-to-brainstem pathway that mediates the sneeze reflex and offering molecular targets for future therapeutic strategies.