Monday, June 1, 2009

A case for smelly boys

Last week, I had the opportunity to attend the conference of the Canadian Association for Neuroscience. It was a fantastic meeting, and in addition to interesting talks from great scientists, there were excellent opportunities to snag free food, which is a surefire way to keep grad students interested. Many talks gave me ideas for this blog, but I settled on an article from Dr Sam Weiss from the University of Calgary. Dr Weiss gave the keynote talk on adult stem cells and his research on new brain cells struck me as relevant in many ways.

Not so long ago, the scientific community believed that you were born with a given amount of brain cells (called neurons). During development, some would die (the whole “use it or lose it” paradigm), and then you’d have more or less a stable number of neurons until you got old, at which point your neurons would start dying again. Essentially, it would be a one-way street: you could never get more neurons, just fewer. Well, lucky for us, it turns out that’s not the case. Neurogenesis, the birth of new neurons, happens throughout your lifetime in two specific regions of your brain: the hippocampus, an important region for memory, and the olfactory bulb, an important part of the brain for the sense of smell. The jury is still out on the significance of neurogenesis and how those neurons are integrated in your existing networks, but there’s a lot of research going on on neurogenesis because, well, it gives us hope that our brains aren’t doomed from age 30 on.

The article from Dr Weiss’ lab looks at how neurogenesis might be relevant for a natural behaviour of both female mice and female humans: how to pick a quality mating partner (a daunting task!). The researchers started by exposing female mice to odors from male mice, and then used a special chemical that dyes newly dividing cells to quantify neurogenesis in the brains of the female mice. After exposing the females to male odors for 2 days, the researchers saw no change in the numbers of new cells in the females’ brains. But after 7 days of exposure, there was a significant increase in proliferating cells in both the hippocampus and the olfactory bulb (I want to say that there’s a message here that guys should be persistent, but I’m not one to extrapolate results like that). Could this observation have been a fluke? It’s unlikely, given the large number of controls in the study. For example, the researchers show that this effect was not present when they simply exposed the females to new odors, it was not present when they exposed the females to odors from castrated males, and it was not present when they used a drug that blocks the females’ sense of smell. So far, I’m convinced.

Now male mice exist in a hierarchy, a kind of pecking order (some would argue just like male humans). Some males are more dominant, others are subordinate. To see if the brains of female mice react differently to dominant or subordinate males, the researchers exposed the female mice to a mix of dominant and subordinate male odors for 2 days (remember, 2 days doesn’t lead to an increase in neurogenesis). This initial phase of the experiment was important to establish memories of these odors. The females were subsequently exposed to either a dominant male odor or a subordinate male odor for 7 days. What the researchers observed then is that females exposed to dominant male odors show a marked increase in new neurons compared to females exposed to subordinate male odors. A biological explanation for the success of the 10-billion-dollars-a-year perfume industry, perhaps?

The last experiment is the most relevant for animal behaviour. Just like the previous experiment, female mice were exposed to a mix of dominant and subordinate male odors for 2 days to establish memories (again, no increased neurogenesis in this time frame). The females were then exposed to either one of the types of male odors for 7 days. The females were later put in a box with 3 compartments side by side (see figure below). The female was in the middle compartment, a subordinate male was on one side and a dominant male on the other. The mice could smell each other but not touch. The purpose of the experiment was to see which of the males would be more interesting to the female (which male she’d choose as a mating partner). Almost without fail, the females previously exposed to a dominant male (those females with increased neurogenesis) preferred the dominant male, while the ones previously exposed to a subordinate male (no increase in neurogenesis) had no preference. But here’s the really neat part: when the researchers used a drug that blocked neurogenesis during the “acquaintance” period with either a subordinate or a dominant male, the females no longer consistently chose the dominant males in the last part of the experiment, regardless of what they had been exposed to previously.

What does this mean? Well, the researchers conclude that male mice have odor signatures and female mice can identify and remember these signatures to carefully select prospective mating partners. Male odors stimulate an increase in new neurons in the female mice’s brains and these new neurons play an important role in selecting the best possible mate. This research is exciting because it means that not only do we make new neurons as adults, but those neurons may actually play a biologically relevant role in our brains. The other reason this research is exciting is because it is looking at an important specie-specific behavior. When studying the brain, many researchers using animal models like to use “humanized” tests and mazes to make the results easy to extrapolate to humans. When an old mouse can’t remember a given spot in a maze, it makes for a good story to suggest that this is akin to an old person not remembering their way home. In this study, I think it’s great that they are studying a phenomenon that we know happens in humans (neurogenesis), but using a real mouse behaviour context to really assess the significance of what they are observing in the greater scope of brain function.

And now, a shameless teaser for my next post: Heard all the hype surrounding the newly discovered “missing link” fossil? Stay tuned for the report of the research paper…

Reference: Male pheromone-stimulated neurogenesis in the adult female brain: possible role in mating behavior. Mak G.K., Enwere E.K., Gregg C., Pakarainen T., Poutanen M., Huhtaniemi I., Weiss S. Nature Neuroscience 2007 10:1003-10.

Experiment diagram from: Alpha males win again. DiRocco D.P., Xia Z. Nature Neuroscience 2007 10:938-40.

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