Harvard Scientists Listen In as Nose Talks to Brain

The smell of a cooking steak is obviously different from, say, three-day-old socks. But the brain has to organize a lot of information to make what seems like a simple distinction.

A group of researchers at Harvard Medical School (HMS) have recently discovered more of the details about how different smells are delivered to the brain—and they may eventually be able to explain why that steak smells so good.

When you get a whiff of a steak, thousands of molecules from the steak bind to different receptors in the nose. The receptors then send signals to the brain, which takes the information and turns it into the sensation you smell.

But there are far fewer types of receptors—about 1,000—than there are smells in the environment, and scientists have been unsure about the exact way the brain sorts them all out.

In the Nov. 8 issue of Nature, however, a research group led by HMS Professor of Neurobiology Linda B. Buck reported that specific receptors in the nose stimulate discrete patterns of neurons in different regions of the olfactory cortex, which is the part of the brain responsible for the sense of smell.

Studying mice, Buck found the patterns for a given receptor were similar among the individual mice.

“We think this is a very important study showing the organizing principles of a sensory system,” said Zhihua Zou, one of the first authors of the study and an HMS research fellow in neurobiology.

These insights may help explain how the brain tells the difference between smells and why certain odors have strong emotional associations—or why sizzling steaks smell so good.

One of the olfactory receptors (ORs) that the study investigated is called M50. According to Zou, when stimulated by a smell, M50 affects the hypothalamus, a part of the brain that, among other things, controls appetite.

“For a mouse, smell could be the most important information for whether it eats or not,” said Zou.

Zou, who worked for three years on the experiments that went into the paper, said that they provide evidence that certain ORs in the nose stimulate specific—and sometimes overlapping—areas of the brain.

“It’s one of the first times that a study has provided data about how information from multiple distinct olfactory receptors are integrated,” HMS Professor of Neurobiology R. Clay Reid said.

The possible overlap of signals from different ORs is surprising because it implies that a single neuron in the brain could be stimulated by more than one type of receptor in the nose.

In the experiments, a single receptor in the nose stimulated about 2 to 5 percent of the neurons in the olfactory cortex. The researchers had expected only about 0.1 percent of the neurons to be stimulated if the signals from receptors did not overlap.

But the overlap may help the brain distinguish different smells.

“To generate a single distinct sense of smell, the signals are probably integrated in the olfactory cortex,” Zou said.

Using a labeling technique that tracked the signal of single type of receptor, the group followed the signals of those receptors all the way to the brain.

Zou said the process of developing the mice used in the study and getting results was sometimes frustrating.

“We had so many problems that we thought about stopping many times,” he said. “But the results are wonderful.”

According to Reid, the study is important for understanding more about how smells are perceived and the work may eventually help in understanding other sensory systems.

“This is a first step in making a meaningful comparison between the olfactory system and other systems,” he said.

—Staff writer Jonathan H. Esensten can be reached at esensten@fas.harvard.edu.