Scientists Create the First Detailed ‘Smell Map’ of Odor Sensors in the Mouse Nose—and Sniff Out Some Surprising Discoveries
In two new studies, researchers used genetic techniques to upend a longstanding assumption that nerve cells with scent detectors were randomly arranged. They don’t know whether the same spatial organization is found in human noses
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How, exactly, the nose’s odor detectors are arranged has long remained a mystery.
Other sensory organs have been charted within the past century, and researchers now know that cells responsible for touch, sight and sound are organized in specific spatial patterns. For instance, hearing a certain frequency triggers precise cells in the inner ear, which then send signals to the brain.
But the nose, scientists thought, was different: It was simply arranged in broad zones.
“Basically, the vibe is, ‘Things are super random, and you can’t make any predictions, and there’s no real spatial structure in the nose,’” Sandeep Robert Datta, a neurobiologist at Harvard Medical School, tells the New York Times’ Emily Anthes.
Now, two studies published April 28 in the journal Cell describe a highly organized smell, or olfactory, system in mice, allowing researchers to start putting order to the chaos. In one, Datta and colleagues mapped more than 1,100 types of odor receptors—proteins attuned to certain scents—in the animal’s nose. The other identified a similar map and offers an atlas of how these receptors connect to the brain.
The work overturns past ideas about olfaction and could help researchers develop new therapies for people who have lost the sensation, which Covid-19 has contributed to. “Smell has a really profound and pervasive effect on human health, so restoring it is not just for pleasure and safety but also for psychological well-being,” Datta says in a statement. “Without understanding this map, we’re doomed to fail in developing new treatments.”
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To chart the receptors, he and his colleagues analyzed roughly five million individual nerve cells, or neurons, from the noses of hundreds of mice. Fine-scale genetic techniques helped them determine where different types of smell receptors were located. Analyses revealed that neurons with similar receptor types are organized into tight horizontal bands from the top to the bottom of the nose.
In the atlas study, another team mapped where certain genes were translated into different olfactory receptors in tissue from the mouse nose and the brain region where odor information is sent. Both research groups ended up with similar maps that were highly consistent between individual mice. What’s more, the brain chart resembled the one in the nose.
“Having this comprehensive understanding … is absolutely essential to understand how we process scent,” Catherine Dulac, a neuroscientist at Harvard University who co-authored the atlas study, tells the Times.
Datta’s team also investigated why the receptors formed a stripe pattern. A molecule called retinoic acid plays a key role, they found. It helps control gene activity and was present in a gradient across the nose, guiding which of the nose’s neurons would express which type of smell receptor.
Fun fact: How does human scent-detection compare?
Humans have an estimated 400 different types of odor receptors. That doesn’t necessarily mean we have a worse sense of smell than mice or other animals with a larger variety.
“There’s been a ton of back-and-forth in the field about how this is all mapped out, and this nails it. I think it really changes the way people think about the olfactory system and just solves a huge problem in the field about how the mapping happens,” says Joel Mainland, an olfactory neuroscientist at the Monell Chemical Senses Center in Philadelphia who was not involved in either study, to Nature’s Chris Simms.
Neuroscientist Alyssa Brewer, who also wasn’t involved, agrees. The work “beautifully resolves a longstanding question about the peripheral olfactory system in mice,” says Brewer, of the University of California, Irvine, to Live Science’s Payal Dhar. “But it opens up an equally exciting set of questions about what happens next, both upstream in the brain and across species.”
Human smell receptors haven’t been mapped, so researchers aren’t sure if they’re organized the same way as in mice. But Datta suspects we have a similar system, per Nature, and is now working to find out.