Mouse Olfactory Receptors Mapped in Detail, Overturning Long-Held Model

Researchers have mapped olfactory receptors in the mouse nose in unprecedented detail, revealing a highly organized structure that overturns a long-standing model of smell detection. The research, published in Cell, shows that around 1,100 olfactory receptors are expressed on sensory neurons in the mouse nose.

These receptors are organized in tightly regulated spatial locations in the epithelial tissue lining the nasal cavity.

The nasal receptor maps match smell maps in the olfactory bulb of the brain. “For 30 years, we’ve taught students that the mouse olfactory epithelium is divided into a handful of broad zones, within which receptor choice is essentially random,” said Johan Lundström, a psychologist and experimental neuroscientist at the Karolinska Institute in Stockholm.

“This is a landmark paper that overturns one of the foundational textbook models of olfactory organization,” Lundström added.

Researchers examined about five million neurons from hundreds of individual mice. They used single-cell sequencing to identify which smell receptors were expressed by neurons in the nose and spatial transcriptomics to map out where key genes are being expressed. The olfactory receptors are arranged in horizontal stripes running from the top of the nose to the bottom.

Each receptor adopts a particular position in the nose, according to Sandeep Robert Datta, a neurobiologist at Harvard Medical School in Boston, Massachusetts. “There are a thousand positions in the nose,” Datta said. Harvard researchers found that the 1,000+ types of smell receptors in mice form tight, overlapping horizontal stripes from the top of the nose to the bottom.

The map is driven by retinoic acid, a molecule that acts as a spatial guide. A gradient of retinoic acid tells each neuron which receptor to express based on its exact latitude in the nose.