One by one, the very earliest stages in our perception of sights, sounds, smells, and taste are giving up their secrets through molecular genetics.
A recent entry: two genes that encode what appear to be taste receptor proteins, newly identified by HHMI investigator Charles Zuker of the University of California, San Diego, and Nicholas Ryba of the National Institute of Dental and Craniofacial Research. The researchers think that the TR1 receptor, which was isolated from the taste buds of rats and mice, may recognize sweet (which usually means nutritious), while the TR2 receptor recognizes bitter. Both receptors seem distantly related to the receptors for pheromones.
But how do signals from sense receptors reach other parts of the brain? And how does the brain interpret these signals and respond to them? Progress has been much slower in this area. Some of the most interesting findings about brain connections that lead to perception come from studies of smellparticularly from the work of Richard Axel and Linda Buck, who have solved long-standing problems in this field.
"One riddle was, how can we remember smells over long periods of time when the olfactory neurons in the epithelium survive for only about 60 days, to be replaced by new cells which have to form new synapses?" says Buck. "Now we know the answer: Memories survive because the axons of neurons that express the same receptor always go to the same location in the brain."
How We Recognize Odors
In March 1999, Buck proved that mammals recognize and process odors through a code based on varying combinations of receptors. She likens olfactory receptors to letters of the alphabet, which can be used over and over again to compose a vast vocabulary.
At the Life Electronics Research Center in Amagasaki, Japan, Buck and her colleagues wafted 30 different odorants over some 600 olfactory nerve cells they had taken from the noses of mice. A special dye inside these cells lit up whenever an odorant receptor had been stimulated. Then, at Harvard, the scientists analyzed each responding cells RNA to identify the olfactory protein it produced. In this way, they found out which receptors had been triggered by which odorants. They concluded that mammals use different combinations of receptors to recognize smells and to distinguish, for instance, between the odors of roses and of goats.
Linking Odors and Behavior
That same month, Axel reported that he had discovered odor-detecting receptors in the fruit fly Drosophilaa finding that could open the way to linking odor perception to behavior. Fruit flies are tractable experimental subjects and have sophisticated scent-sniffing organs, which they use to recognize a large repertoire of aromas. Axels team identified 11 genes that encode Drosophila odor receptors. He estimates they belong to a family of between 100 and 200 genes and plans to use these genes to study how specific odors influence the flies behavior.
If his group succeeds in identifying the receptors that are activated by odors that induce mating, for instance, the researchers may be able to map the neural circuitry of the mating response. This could lead to a simple way of preventing crop-eating insects from reproducing. Going further, Axel hopes to link certain olfactory connections in the flies brains to specific kinds of learning and memory.
The Erotic Nose
Exploring the vomeronasal organ, or VNO, which some scientists now call "the erotic nose," two teams of researchers announced in April 1999 that they had mapped out how sensory neurons in the VNOs of mice connect to specific areas of the accessory olfactory bulbs.
One team was led by Peter Mombaerts of the Rockefeller University; the other was led by two HHMI investigators, Catherine Dulac of Harvard University and Richard Axel. Both groups suggest, but have not yet proved, that pheromones bind to special receptors on sensory neurons in the VNOs of mice. This is difficult to demonstrate, they point out, because very few mammalian pheromones have been identified.
Do Humans Sense Pheromones?
The best evidence that humans communicate through pheromones comes from Martha McClintock, who in 1998 completed a study in which she manipulated the timing of womens menstrual cycles. Every day for two months, she and Kathleen Stern of the University of Chicago collected cotton pads from the armpits of nine women in various phases of their ovulatory cycles and then wiped these pads just under the noses of 20 other women, who were asked not to wash their faces for the next 6 hours. The recipients did not know the source of the compounds and could smell only the alcohol, which served both as a control and as a carrier of the compound.
Women who had been exposed to pads from women in the follicular phase (before ovulation) ovulated earlier, shortening their menstrual cycles. However, pads taken from the same donors during their time of ovulation had the opposite effect, delaying the recipients ovulation and lengthening their menstrual cycles. "This study provides definitive evidence of human pheromones," the researchers say. "Well-controlled studies of humans are now needed to determine whether there are other types of pheromones, with effects that are as far-reaching in humans as they are in other species."
Researchers still do not know how humans sense pheromones, however. Ifunlike the VNOs of micethe human VNOs turn out to be nonfunctional, humans may sense pheromones through ordinary odor receptors in the nose, after all.
Top of page
Researchers Discover Human Gene that May Produce Sweet Taste Receptor
April 23, 2001
Researchers Identify Fly Genes
March 9, 2001
Bitter Taste Receptors Identified
March 17, 2000
Drosophila Odorant Receptors Identified
March 15, 1999