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Learning to read mouse pee
1 MAY 2008

A mouse in the house: Reading the signals of urine
For an itty-bitty organ hidden inside the nose, the vomeronasal organ carries a lot of clout -- if you are one of the many vertebrates that respond to chemicals called pheromones. Scientists have long known that the vomeronasal organ (VNO), a sort of parallel olfactory system, is critical to male territorial aggression and mate selection among mammals, but few have looked at exactly how VNO neurons pick up the signals and transmit them to the brain.

The vomeronasal organ is a sort of parallel olfactory system that is essential to male territorial aggression and mate selection. A mouse study shows how it works.

In both the VNO and the olfactory sense -- what we civilians call "smell" -- neurons are studded with receptors that can each identify particular chemicals. Mice typically use urine to mark territory and attract mates, and now a study shows how nerve cells in the mouse VNO can detect pheromones carried in mouse urine. Pheromones are trace compounds that inform the sniffing mouse about the status of the urinating mouse.

Image shows long, skinny neurons, ending at the same plane.

The mouse vomeronasal organ responds to chemicals in the environment. With a separate connection to the brain, it is a sixth sense that tells the mouse about the sex, mating status and identity of another mouse -- based on compounds in urine. Courtesy C. Ron Yu, Stowers Institute for Medical Research

Researchers in C. Ron Yu's lab at the Stowers Institute for Medical Research tested mice carrying a gene that caused VNO neurons to light up when they picked up whatever particular pheromone they were programmed to detect. By associating the activity of specific neurons to the urine of individual animals, the researchers found that males and females both devote about 1 percent of their VNO receptors to detecting urine from males and 2.6 percent of them to detecting urine from females.

Bright spots show activation of vomeronasal neurons after they detect urine from a male mouse. Courtesy C. Ron Yu

A separate group of VNO neurons detected females in estrus, meaning they were ready to mate.

Because the mouse has about 250 varieties of VNO neurons, each primed to detect a specific pheromone, the response pattern was uniquely associated with the urine of a particular mouse. Thus the VNO system would enable a mouse to identify individuals, based solely on urine.

All of these abilities have obvious value in helping mice identify potential mates, but the VNO may be doing other things as well, since only about 40 percent of the VNO receptor cells responded to mouse urine. The others may be responding to non-urinary cues or to the urine of other species, says Yu, a neuroscientist who specializes in the olfactory system.

Human impact
At first blush, this stuff may be interesting. But it's irrelevant to humans, which, Yu says, probably lack a working VNO. "Most mammals have the vomeronasal organ, but in most primates, including humans, it is vestigial," he says. And despite the repeated assertions (perfume-makers, are you tracking?) that humans do respond to pheromones, Yu says that most of the genes needed to make VNO receptors in primates are silent.

He does admit, however, that pheromones may work through our sense of smell. Nevertheless, the study does have a couple of implications for us top primates. For one thing, the mice can identify an individual mouse by looking at several pheromone signals, and thus a relatively simple system can be used to identify a vast number of individuals.

A couple, backlit, with lake and sailboats before them. She smiles, his arm is around her.

Romance is in the air at the Memorial Union Terrace at the University of Wisconsin-Madison. Any chance these folks communicate with pheromones? 2003 photo by Jeff Miller, University of Wisconsin-Madison.

The same system may work in our brains, Yu says. "We don't necessarily have a cell dedicated to recognizing a particular object [although we wonder if a dollar-detector is evolving... ]. We observe different features of the object, and then can generalize."

And humans, like mice, can make an identification without looking at all available data, Yu adds. A guitar, for example, has six strings, a neck, frets, a body with (originally) a tone hole. But even if John Lee Hooker plays a guitar without tone holes, we can recognize his axe as a guitar rather than an oboe. Adding up signals, Yu says, "is a very robust way of encoding sensory input."

A difference in the brain
A second implication concerns where the sensory inputs enter the brain. Although both the olfactory system and the VNO alert the brain to the presence of chemicals in the environment, the information goes to different locations. Olfactory neurons connect to the cortex, a site of higher information processing, and "are probably able to generate some kind of learned association between the sensory input and behavior," Yu says.

Like this: "Hmm ... smells like cheese, but I notice it smells spoiled. Based on experience, I better nibble, not gobble."

The VNO, in contrast, "directly activates some endocrine [hormonal] or emotional sensors," says Yu. "We know pheromones trigger innate behaviors that do not require learning."

Like this: "Receptive female ahoy. Defend your territory!" (Except that the signal is automatic, not learned.)

Although humans don't have a VNO, Yu says, some of our senses may connect to less thoughtful parts of the brain, as well as to the cortex. A sudden clang, for example, may start the "startle response," triggering an immediate defensive action, "so you don't have to process everything through the cortex before you react," he says.

Similarly, Yu says, the main olfactory system may connect to the amygdala, an emotional center of the brain. In this way, a smell "could provide a much quicker relay, some kind of primal reflex" that would not require any further mental processing, he says.

Like this: "Stinks like mouse pee. Ecch. I'm outta here!"

-David Tenenbaum

• Encoding Gender and Individual Information in the Mouse Vomeronasal Organ, Jie He et al, Science 320, 535 (2008).

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Running head image mouse: Oak Ridge National Laboratory

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