Whether it’s pine trees in a forest or coffee brewing, every odor triggers a process inside the nose that activates a unique combination of cells that signal the brain to identify the odor. The sense of smell plays an important role in preferences and aversions for aromas, specific foods, and flavors. It also provides a warning system, alerting us to danger signals such as a gas leak, spoiled food, or a fire.
The number of possible cell combination patterns to identify the many thousands of odors in the environment is huge, and researchers seeking to understand these patterns have been limited by current methods used to study the mechanisms involved in our sense of smell. Presently, cell-based assays and mice carrying genes from other species (transgenic) are used to identify which odorant receptors are activated by certain smells. However, transgenic models are limited in the number of odorant receptors that can be tested at a given time, and cell-based assays are limited because they are unable to copy mucus-like conditions found in the nose. Now, a novel method developed by NIDCD-supported scientists from Duke University provides a new resource to identify the molecules and mechanisms involved in odor detection. The study’s findings were published online on August 31, 2015, in the journal Nature Neuroscience.
The ability to smell depends on specialized sensory cells, called olfactory sensory neurons, which are found in a small patch of tissue inside the nose. These cells connect directly to the brain. Each olfactory neuron expresses one odorant receptor gene. There are a large number of odor receptor genes—mice have about 1,000 and humans have about 350. When odor molecules are released by substances around us, they stimulate these odorant receptors. Once the neurons detect the odor molecules, they send messages to the brain, which identifies the smell.
The Duke researchers, led by Yue Jiang, Ph.D., and Hiroaki Matsunami, Ph.D., developed a new method in mice that automates the process to identify a large number of odorant receptors that respond to specific smells. This model improves upon existing methods because it is not limited to the number of odorant receptors that can been tested at a given time; in addition, the model more accurately mimics conditions found in humans.
There are many more smells in the environment than there are odorant receptors, and any given odor molecule may stimulate a combination of odorant receptors, creating a unique activation pattern for a particular smell. Scientists are in the early stages of understanding the complexity of the relationship between the many odors that we encounter every day and odorant receptors.
“One odor activates a certain subset of odorant receptors, but which receptors are activated is largely unclear,” said Dr. Matsunami. “In this study, we developed a new in vivo method using laboratory mice that allows the pairing of any odor with the receptors that it activates.” The method is also advantageous because it can be performed in active mice and more readily simulates real-life situations. This allows scientists to screen for all mouse odorant receptors and greatly increases their ability to provide a comprehensive understanding of the odorant receptor activation patterns.
Using this technique, the researchers isolated and examined the genetic material from olfactory sensory neurons in mice that were activated by a specific odor. They were able to identify the odorant receptors that responded to the odors. The researchers also observed similarities between odorant receptors that respond to a given odor and were able to predict similar responses in other odorant receptors.
The researchers are also expanding the list of chemicals available for detecting odorant receptors. This will allow for a more complete matching between receptor and odorant to better understand how odors are coded in the nose.