Buck’s Research Helps Unravel Mysteries of Scent
Photo: Bill Branson
“Through the sense of smell, humans and other mammals can detect a vast array of chemicals in the environment,” said Buck, Nobel laureate (2004) and full member of the basic sciences division at Seattle’s Fred Hutchinson Cancer Research Center, at the annual Margaret Pittman Lecture recently in Masur Auditorium.
Smell is governed by the olfactory system, which she notes “is characterized by exquisite sensitivity and discriminatory power.” Certain odors trigger changes in reproductive and stress hormones or cause instinctive aggressive or fearful behavior.
“All of these so-called odorants are small molecules, but somehow they are perceived as having different odors based on their different structures,” she explained. If the molecular structure of an odorant changes—even slightly—the perception changes. That’s why pear and banana odorants, for instance, have similar molecular structures but don’t smell the same.
Buck said, in mouse studies, odor signals move through two neural pathways in the brain: the main olfactory pathway and the vomeronasal pathway.
When odorants enter the nose, olfactory sensory neurons activate. These neurons are found in the olfactory epithelium lining the nasal cavity, an air-filled space above and behind the nose.
The neurons transmit signals to the main olfactory bulb, an area of the brain. More specifically, the neuron signals converge on areas of the bulb called glomeruli. From there, the signal moves to the olfactory cortex and, finally, to other areas of the brain thought to control perception and deep limbic areas such as the amygdala and hypothalamus, parts of the brain influencing basic drives and emotions, including fear.
The olfactory system can also detect pheromones, chemicals that influence basic drives and instinctive behaviors, through both the main and vomeronasal pathway. Vomeronasal neurons transmit signals through another region of the olfactory bulb and then travel to the amygdala and hypothalamus.
Photo: Bill Branson
In 1991, Buck and her then-colleague Dr. Richard Axel first discovered odorant receptors while studying rodents. There is one type of receptor in each olfactory sensory neuron. Each receptor can detect multiple odorants and each odorant can be detected by multiple receptors. Humans have roughly 350 different receptors, while mice have about 1,000. Millions of sensory neurons populate the olfactory epithelium.
“The olfactory receptor gene family is the largest one known. It comprises about 1-4 percent of all known genes in humans and mice,” Buck said.
Her lab is now studying how the olfactory system stimulates instinctive behavioral changes in mice. In one recent study, mice were exposed to bobcat urine or TMT, a component of fox odor. Researchers in her lab used an engineered virus to identify the region in the olfactory cortex that’s associated with the fear response.
“Predator odors can induce instinctive fear responses in mice that include instinctive behavior as well as increases in blood stress hormones,” she said.
Buck and her colleagues discovered a tiny region of the cortex responsible for the hormonal response. This area is called the “amygdalo-piriform transition area,” or AmPir. When artificially activated, the AmPir stimulated the release of stress hormones.
And when blocked, there was no hormonal response to predator odors. However, the animals still froze when exposed to predatory odors. Buck suspects the hormonal and behavioral responses are controlled by different areas of the olfactory cortex.