Every deliberate sniff may activate a brain system that has survived millions of years of evolution.
A mouse searching for food may sniff several times each second. A person checking whether a cantaloupe is ripe usually leans in for one slow, deliberate breath.
Those behaviors look completely different, but new research suggests the brain may treat them in much the same way.
Two complementary Northwestern University studies found that mice can perform a single intentional sniff, while humans use brain rhythms that closely resemble those seen in rapidly sniffing rodents. Together, the findings suggest mammals share an ancient neural system for gathering information through smell, even when their breathing patterns and behavior differ dramatically.
The studies were published together in Science Advances.
“The true similarity is this single sniff, but it’s not just a sniff,” said corresponding author John M. Barrett, research assistant professor of neuroscience at Northwestern University Feinberg School of Medicine. “Mice even move their hands while sniffing, which shows it’s volitional; they’re doing it on purpose.”
Different Sniffs, Same Brain Process
Smell begins with breathing, but it is not a passive sense. Animals actively control when and how they inhale, changing the flow of odor molecules into the nose and shaping the information sent to the brain.
Rodents are especially known for rapid sniffing. Humans breathe much more slowly, which raised a long-standing question: How can both species identify odors with similar speed and precision when their sampling rates are so different?
The Northwestern teams approached that puzzle from opposite directions. One group studied how mice coordinate breathing and movement while examining food. The other recorded activity directly from the human olfactory bulb, the brain structure that receives the earliest neural signals from the nose.
Their results converged on the same conclusion. Humans and mice appear to rely on a shared timing system for processing smells.
Why Sniffing Could Reveal Disease
That similarity matters because changes in sniffing have been associated with autism, Alzheimer’s disease, and Parkinson’s disease. Understanding how healthy smell circuits operate could help researchers recognize when those systems begin to break down.
“Knowing we have this evolutionarily conserved set of mechanisms helps us understand how mammalian brains work, which could ultimately help us understand how they fail in pathology,” said first author Andrew Sheriff. “It helps us know how the brain works so we know how to fix it when it doesn’t work.”
The mouse study began with a small behavior that was easy to overlook. When mice handled food, they sometimes d and lifted it toward their noses before eating. Rather than continuing their usual rapid sniffing, they appeared to take one carefully timed breath.
Researchers in the laboratory of Gordon M. G. Shepherd in the Department of Neuroscience at Northwestern University Feinberg School of Medicine worked with collaborators at the University of Pennsylvania and the University of Florida College of Medicine to investigate.
Led by Mang Gao and Barrett, the team created a robotic multi-camera system that followed freely moving mice as they searched for food and ate. The researchers tracked breathing along with movements of the animals’ heads and forepaws.
Breathing and Movement Work Together
The recordings showed that the mice timed one sniff to the exact moment food reached the nose. Their breathing, head position, and hand movements came together as a coordinated action.
This was not the same as the repetitive sniffing mice use while searching. It looked more like a quick inspection, similar to the way a person may raise food to the nose before deciding whether to take a bite.
The mice sniffed more strongly when handling less appealing food. However, odor alone did not trigger the behavior. When researchers disrupted the animals’ sense of smell, the mice continued performing the single food sniff. The behavior stopped only when the scientists silenced the motor cortex, a brain region involved in voluntary movement.
“This means when mice sniff food, they’re not doing it as a reflexive response to an odor, but rather as a proactive act of deliberate sensory sampling,” said Gao, a postdoctoral scholar in the Shepherd lab. “It turns out the mice choose to perform these quick ‘smell checks,’ which is characteristic of a lot of human olfactory behavior, rather than being passively triggered to sniff.”
The study is the first to document this intentional, non-reflexive sniffing behavior in rodents during natural foraging.
How Humans Process Odors So Quickly
The second study examined the problem from the human side. Researchers in Christina Zelano’s laboratory in the Department of Neurology at Feinberg, working with Dr. Bruce Tan in the Department of Otolaryngology at Feinberg, wanted to understand how people can recognize smells quickly despite inhaling far more slowly than rodents.
“We wanted to understand how we can identify odors as fast as rodents do even though we sniff over 10 times slower,” said Sheriff, a postdoctoral scholar in Zelano’s lab. “By recording directly from the human olfactory bulb using a novel technique, we were able to find rhythms of odor processing that closely resemble those of rodents, suggesting conserved time windows for olfaction across species.”
Using a minimally invasive, high-precision method developed in the Zelano lab, the team measured activity in the olfactory bulbs of healthy volunteers as they took one intentional breath. That single inhalation triggered low-frequency brain waves known as theta oscillations (2–8 Hz). The rhythm matched the same frequency range at which rodents repeatedly sniff.
One Breath, Multiple Brain Cycles
This means the human brain does not need to match each theta cycle with a separate breath. Instead, one slow inhalation can activate several internal processing cycles, allowing odor information to be divided and organized rapidly within a single sniff. The theta rhythm also helped structure faster bursts of neural activity associated with analyzing the smell itself.
In rodents, breathing and theta activity are so closely synchronized that they are difficult to separate. Human breathing is slower, making it possible to see that the brain rhythm can continue independently of the physical sniff.
“The implications of our findings are significant,” said co-author Qiaohan Yang, a graduate student in Northwestern University Interdepartmental Neuroscience. “In rodents, sniffing and theta are so tightly fused that the two are nearly indistinguishable. In humans, the slower sniff rate pulls them apart, revealing the theta oscillation as a distinct, independently generated rhythm that a single deliberate inhalation is sufficient to engage.”
Smell Is an Active Decision
The studies add to a broader understanding of perception as something the brain actively constructs.
A sniff is not simply air entering the nose. Its timing can be coordinated with movement, attention, expectation, and decision-making. Mice appear to choose when to perform a focused smell check, while the human brain uses one breath to create a rapid internal sequence for analyzing odor.
The difference between species may therefore lie less in the basic machinery than in how each animal uses it. Mice run the shared system through rapid breathing cycles. Humans compress similar neural timing into a slower inhalation. Both strategies allow the brain to collect information quickly enough to guide the next action, whether that means eating a crumb, rejecting spoiled food, or deciding that a piece of fruit is ready.
Together, the studies suggest that evolution did not invent a completely new olfactory system for humans. It retained the same core design and adjusted how that design operates within a very different pattern of breathing and behavior.
References:
“Dexterous single sniffs for ethological active olfaction” by Mang Gao, John M. Barrett, Rita Fischer, Donald R. McCrimmon, Daniel W. Wesson, Minghong Ma and Gordon M. G. Shepherd, 3 July 2026, Science Advances.
DOI: 10.1126/sciadv.aed3610 “Theta oscillations are an organizational unit of odor processing in the olfactory bulb” by Andrew Sheriff, Mahmoud Omidbeigi, Gregory Lane, Qiaohan Yang, Guangyu Zhou, Adam Dede, Naelly Arriaga, Vivek Sagar, Ania M. Holubecki, Rodrigo M. Braga, Leslie M. Kay, Bruce K. Tan and Christina Zelano, 3 July 2026, Science Advances.
DOI: 10.1126/sciadv.aee1002 Funding for the mouse study was provided by the National Institutes of Health (NIH). Funding for the human study was supported by the National Institute on Deafness and Other Communication Disorders of the NIH.
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