A Nose for Research
using the nose to unlock the mind
PrintWhen you were a kid and a friend asked you, “If you had to lose one of your five senses, which would you choose?” you undoubtedly chose smell. The olfactory system, which includes your nose and the areas of the brain that enable you to interpret scents, has always been a bit of an underdog. In the laboratory of Dr. Stuart Firestein, however, Columbia neuroscientist and professor, the nose becomes a window into the secret lives of neurons.
Don’t let his broody walk and quintessential grey-professor-hair fool you. Firestein is a decidedly West Coast intellectual. His manner is easy and, when it comes to research, he’s in it for the adventure. “I’m really interested in the brain,” he says, “but that’s too big, so I’ve picked on a part of it, which is the nose.” He studies olfaction not only as a sensory system, but also as a model for some of the brain’s most fundamental and mysterious processes.
Currently, Firestein and his team have two major research topics: development and ageing. Using the mouse olfactory system as a model, they are exploring how the growth of new brain cells is regulated and tracking how neurons move and change over time. These topics are difficult to study in humans because they take, well, a lifetime. The short lifespan of the mouse (about 18 months) makes it possible for scientists to study the processes of brain development and ageing as discrete, repeatable phenomena.
The olfactory system is a particularly apt model for development because it has an unparalleled ability to make new neurons. While most areas of your brain are lucky to gain a few neurons per year, the olfactory system gets 30,000 new cells a day. “That’s a lot of neurons. You’d think it would itch or something,” jokes Firestein. The large-scale proliferation, and the quick turnover (each neuron lives only 3 to 4 months), make the olfactory system an efficient model for human development and ageing.
“For us,” he says, “the question is not only how do these cells regenerate, but how do the new cells integrate into an existing brain. That’s a big question.” There are between 300 and 1000 different kinds of neurons in your nose, each detecting a different smell and sending a message along a specific pathway to the brain. Firestein is trying to figure out how new cells are able to replace older cells to such an extent and so quickly in this complicated network.
Firestein studies this process by tagging certain neurons and following them around the olfactory system. He uses a marker called green fluorescent protein that, once delivered to a neuron, makes it glow green whenever a UV light is shined on it. “If we inject on Wednesday, we can look at the mouse six months later, and know that the marked cells were born at 4:00 in the afternoon on Wednesday April 8th. This gives us a way of birth-dating cells.” Firestein uses this technique whenever he needs to see where a neuron is going.
Right now, Firestein’s lab is carrying out an experiment to explore how the production and integration of new neurons in the olfactory system is regulated. Using a technique similar to radiation therapy for cancer, they destroy the new olfactory neurons being produced in the brain and track the unscathed, mature neurons to see how they respond and if they still die off at their usual rate. “Results are never as clear as you’d like,” says Firestein, “[But] somewhat to our surprise, if you cut off the supply of new cells, the old cells seem to know this and they stay around much longer.” His team is working to uncover how this regulation system works, and whether it can shed light on how neurons communicate and “know” where to go in an already-established system.
In another vein of research, Firestein asks: Does the ability to produce new cells decrease as an animal ages? When a mouse is about a year old (approximately 50 in human years), it stops producing as many new olfactory neurons. If the mature neurons in an aged mouse’s nose are destroyed however, it starts producing new neurons at a much faster rate in order to compensate. The capacity to produce new cells is not lost; it’s just turned off somehow. “So one wonders, is this happening to us? Even in our skin: As a person gets older, their skin loses elasticity, loses tone, but if you cut them, they heal—they do make new skin cells. And is that what’s going on in our organs?”
One quality that Firestein has not yet examined is just as intriguing: why it is the only sense that connects directly to the primitive brain structures that govern emotion and memory without first being passed through higher levels of processing. Your nose is why when you catch a whiff of your ex’s cologne you get much more vivid, visceral memories than you would from hearing their name or seeing their picture.
Firestein has decided to put off this question for the moment. “It’s another area that interests us, and I’m sure we’ll get to it eventually,” he says. Even when he’s looking through a microscope, Firestein has his eye on the big picture: how olfaction relates to the brain as a whole. With his daring approach to research, the underdog of the senses may become a model for the greatest mysteries of neuroscience.
*Correction: The original sentence, "One quality that Firestein has not yet examined is just as intriguing: why it is the only sense that connects directly to the primitive brain structures that govern emotion and memory," was not completely correct. All of the senses connect to these brain structures, but
only olfaction connects directly without first being passed through higher levels of processing. The sentence has been appended, and we apologize for the error.
23 April 2009
vol. 6, issue 11
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