Olfaction Like Humans, Mice Can Take a Single Sniff to Deliberately Probe their Environment

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New research has found that like humans, mice also can take a single sniff to deliberately probe their environment — something scientists previously did not know.

Chicago/USA – Picture a mouse taking rapid, staccato sniffs of a crumb it’s found while foraging for food. Now compare that with a human, leaning in for a single, deep inhale to gauge if a cantaloupe is ripe. New research from Northwestern University has found, like humans, mice also can take a single sniff to deliberately probe their environment — something scientists previously did not know.

Two new complementary Northwestern University studies, published together on July 3 in Science Advances, studied olfaction from opposite ends and found rodents and humans rely on the same underlying neurophysiology — the brain’s motor and rhythmic building blocks — to process smells. Although a mouse’s single sniff is much shorter than a human’s, the underlying tempo of smell processing is the same, according to the findings. The results suggest these sensory systems are fundamentally similar and have been preserved through evolution.

Taken together, the findings from the two labs suggest something important: Mammals all rely on a similar underlying system for smell, with each species putting its own twist on the same basic design. The work answers a fundamental question: How do mice and humans sample our environment so we understand it and predict the next thing we want to do?

“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.”

What are the implications for humans?

Behavioral changes in sniffing are linked to conditions like autism and Alzheimer’s and Parkinson’s diseases, so understanding the olfaction system’s basic wiring could help with earlier detection or better treatments, the study authors said.

“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.”

A tale of two papers

One study found mice inspect their food using single sniffs that look remarkably human-like. The other found humans organize odor information at a rapid rate within a single sniff, in a form of olfactory brain processing that looks remarkably rodent-like. Together, these separate but complementary studies suggest there are shared, fundamental biological rules behind how these two mammals’ senses of smell work, and that these have been preserved through evolution.

First study: mice can sniff like humans

The first paper began with a simple observation: When mice handle food, they’ll occasionally bring it briefly to their noses before continuing to eat.

The study was conducted in the lab of Gordon M. G. Shepherd in the department of neuroscience at Northwestern University Feinberg School of Medicine, along with colleagues locally and at the University of Pennsylvania and University of Florida College of Medicine.

The team built a robotic multi-camera recording system to follow mice around as they forage and eat. Led by Mang Gao and Barrett from the Shepherd lab, the scientists tracked at high resolution the mice’s hand and head movements while simultaneously tracking their breathing.

The mice timed a single sniff to the exact moment the food reached their nose, precisely coordinating their hands, head and breathing. Unlike the steady sniffing they use when searching for food, this behavior is quick and deliberate, much like when a human lifts food to their nose for one careful smell before taking a bite.

The mice sniffed more vigorously when handling unappetizing food, the study found, but it was not only the presence of odor that drove the behavior. When the scientists interfered with the mice’s sense of smell, they continued performing food sniffs as normal. What ultimately stopped the behavior was silencing the motor cortex — the region of the brain associated with conscious, intentional 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.”

This is the first study to document this intentional, non-reflexive sniffing behavior among rodents in a real-world setting.

Second study: humans can process odors like mice

The second study, from the lab of Christina Zelano in the department of neurology at Feinberg, in collaboration with Dr. Bruce Tan in the department of otolaryngology at Feinberg, sought to answer how humans can achieve the same perceptual precision as rodents with a single, slow sniff.

“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.”

The team used a minimally invasive, high-precision method developed in the Zelano lab to record sniffing in the brains of healthy human volunteers. When participants breathed in a single intentional inhalation, it elicited low frequency brain waves called theta oscillations (2–8 Hz) in the human olfactory bulb, at precisely the same frequencies at which rodents sniff. This slow brain rhythm helps organize faster bursts of activity that happen when the brain is actually processing a smell, the study found, meaning the human brain can generate the theta rhythm from a single sniff and use it the same way rodents use their sniff cycle.

“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.”

Funding for the mouse study was provided by the National Institutes of Health (NIH) (grants R34DA059723 and R37NS061963). Funding for the human study was supported by the National Institute on Deafness and Other Communication Disorders, of the NIH (grants R01DC016364, R01DC018539 and R01DC021663 to CZ) and NIH training grant T32 NS047987.

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