By mapping millions of smell-sensing neurons in mice, scientists discovered precise striped patterns inside the nose, overturning decades-old assumptions about how olfaction is wired.
A cross section of a mouse nose. Image credit: Datta Lab, Harvard Medical School.
“For most of us, the sense of smell is an integral part of everyday life,” said Harvard Medical School’s Professor Sandeep (Robert) Datta.
“It plays a critical role in providing information about our surroundings, alerting us to potential dangers, enhancing our sense of taste, and evoking emotions and memories.”
“Yet from a scientific perspective, olfaction is super-mysterious.”
Working in mice, Professor Datta and colleagues discovered that unlike what scientists had long believed, the neurons expressing these receptors have a high degree of spatial organization: they form horizontal stripes based on receptor type from the top of the nose to the bottom.
Moreover, they established that the receptor map in the nose matches up with smell maps in the olfactory bulb of the brain, providing clues about how information moves from the nose to the brain.
“While the smell map is an exciting discovery in its own right, it also provides foundational information that could help scientists develop therapies for loss of smell, which are currently lacking,” Professor Datta.
“We cannot fix smell without understanding how it works on a basic level.”
“Maps have long existed that describe how receptors in the eye, ear, and skin are organized to capture and interpret auditory, visual, and touch information. And scientists have figured how these maps correspond with those inside the brain.”
“However, olfaction has been the one exception; it’s the sense that has been missing a map for the longest time.”
In the new study, the researchers combined single-cell sequencing and spatial transcriptomics techniques to examine around 5.5 million neurons in more than 300 individual mice.
The first technique allowed them to identify which smell receptors were expressed by neurons in the nose, and the second let them determine the locations of those receptors.
“This is now arguably the most sequenced neural tissue ever, but we needed that scale of data in order to understand the system,” Professor Datta said.
The scientists discovered that the neurons are organized into tight, overlapping, horizontal stripes from the top of the nose to the bottom based on the type of smell receptor they express.
This highly organized receptor map was consistent across the mice and mirrored the organization of smell maps in the brain, just like researchers have observed in vision, hearing, and touch.
The authors then investigated how the smell map in the nose forms and identified retinoic acid — a molecule that helps control gene activity — as a key driver.
They found that a gradient of retinoic acid in the nose guided each neuron to express the correct type of smell receptor based on its spatial location.
Adding or removing retinoic acid caused the receptor map to shift up or down.
“We show that development can achieve this feat of organizing a thousand different smell receptors into an incredibly precise map that’s consistent across animals,” Professor Datta said.
A paper describing the results was published in the journal Cell.
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David H. Brann et al. A spatial code governs olfactory receptor choice and aligns sensory maps in the nose and brain. Cell, published online April 28, 2026; doi: 10.1016/j.cell.2026.03.051
