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“Social Smell” Discovered In Mice
Researchers isolate the chemical that defines mouse maleness

Contact: Catherine Herman (518) 437-4980

ALBANY, N.Y. (March 4, 2005) -- In experiments with mice, a team of scientists including UAlbany chemist Eric Block have found the first evidence of neurons responsive to social odors, using a new analytical approach to isolate one of these social odors -- a novel sulfur-containing chemical in urine that enables mice to distinguish between the sexes -- defining maleness in the mice.

The neurons were discovered in the mice's main olfactory system, a group of brain structures used to process smell. Until now, it has been believed that most chemical social signals in mammals are detected by a different system, the accessory olfactory system, that is absent in humans. The researchers said their findings that mice also use their main olfactory system to detect social signals suggest that humans too may communicate via social odors, because humans possess the same set of brain regions.

The researchers, led by Howard Hughes Medical Institute investigator Lawrence Katz at Duke University Medical Center and Distinguished Professor of Chemistry Eric Block at the University at Albany, State University of New York, together with Da Yu Lin in Katz’s lab and Dr. Shao-Zhong Zhang in Block’s lab, published their findings February 20, 2005, in the online edition of the journal Nature.

The researchers used a new combination of analytical techniques to isolate volatile compounds from mouse urine and trace their effects on the neural odor-processing circuitry. Besides mapping the odor effects in the brain, they also isolated a novel sulfur-containing chemical that may enable mice to identify another individual as male or female. They demonstrated that the presence of this chemical in male mouse urine substantially enhances the attractiveness of males to female mice. Importantly, this chemical is only found in male mouse urine, not in urine from female mice or in castrated male mice that lack sex hormones.

“These represent the first comprehensive study of how a complex social stimulus like urine is represented in the olfactory bulb, which is a system that both humans and other mammals possess,” said Katz. “The results were very clear and really quite surprising. We found that in a complex mixture like urine, which has at least a hundred compounds in it, an individual nerve cell in the olfactory bulb acted as a detector for just one of those compounds. This finding will help settle a continuing debate among scientists studying the olfactory system -- whether olfactory neurons are broadly tuned, responding to many different compounds, or whether they act as olfactory feature detectors,” said Katz.

The researchers’ mapping revealed that only a very small area of the olfactory bulb responded to the urine volatiles, said Katz. In particular, Lin and Katz noticed that one component present in only infinitesimal amounts and only in male urine nevertheless evoked a particularly strong response in the mouse neurons. Their analysis suggested the presence of a novel sulfur-containing compound. To confirm the compound’s identity, UAlbany's Eric Block, an authority in the chemistry of organic compounds of sulfur (such as those from garlic, onions and mushrooms), and postdoctoral fellow Zhang synthesized possible candidate molecules, and the researchers tested their effects on neuronal responses. This analysis revealed the compound to be (methylthio)methanethiol, or MTMT. The researchers found MTMT in the urine of intact male mice, but not in urine from females or castrated males, and found that the females were much more attracted to urine containing MTMT, but not to urine that did not contain the compound.

Block said, “It was quite amazing to us that this stinky little molecule, having only ten atoms and present at levels corresponding to only a few molecules mixed with a billion others in a mixture as complex as urine, was able to elicit a strong positive response from female mice. We can now add mice to the list of other animals -- skunks, ants, hamsters, mink, hyenas -- that use small sulfur molecules for social signaling and defensive purposes.” Block said that there is “an important additional piece of information conveyed by the urine sulfur compound, namely that small variations in the levels of MTMT could indicate to other mice the freshness of the urine. This is because other sulfur-containing compounds in mouse urine, or even oxygen in air, can react with MTMT and thereby gradually decrease MTMT concentrations over time.”

Katz said, “There are persistent reports about the influence of odorant communications in all sorts of behavior in humans -- mothers recognizing infants, wives recognizing husbands and of course the influence of perfumes and colognes. Since we’ve found that mice -- which are well known to use odors for social communications -- do so using the main olfactory system, this strongly suggests that sex-specific volatile chemicals in our bodily secretions could also be detected by similar circuitry.” In further studies, Katz and his colleagues are using a vast array of odors, both synthetic and natural, to decipher the olfactory “code” by which the brain constructs elaborate olfactory scenes from combinations of odorants. They also seek to understand how mice combine information from multiple odors to recognize other individual mice, much as humans recognize other individuals by their faces. Such studies may yield insights into the formation of human perception, which enables recognition of specific objects in the environment by combining multiple components, be they visual, auditory or olfactory, said Katz.

“The question is how do you know a rose is different from a skunk, or how a merlot is different from a cabernet?” asked Katz. “It’s because we have a sophisticated olfactory discrimination system that relies on detecting and integrating information from a distinctive set of chemicals."

“One of the important questions remaining to be answered is specifically how a volatile small molecule such as MTMT is recognized by the receptor proteins found in the olfactory bulb. A sustained team effort is needed to solve this riddle, the solution to which will greatly advance our knowledge of this least understood of all of our senses, the sense of smell,” said Block.

Editors: Eric Block may be reached at (518) 442-4459 (W) or (518) 370-1235 (H); e-mail eb801@albany,edu; Lawrence Katz may be reached at (919) 681-6225, e-mail [email protected].

Advance copies of the report are available in PDF format:
https://www.albany.edu/news/pdf_files/NATURE03414_proof1%20copy.pdf