Visualizing Scent Networks in the Olfactory System
Dr. Leonardo Belluscio
April 2001 - It has happened to everyone. A scent fills the air and suddenly you are transported across memory space to another place and time. It may be the scent of new-mown hay or grandma’s peach pie – the ability of smells to evoke vivid memory is a near universal experience.
Yet the sense of smell is probably the least studied and least understood of our senses. It has lagged behind studies of sight, hearing, and even touch. Part of the reason is likely that, as humans, sight and hearing are our dominant senses and are given greater importance. Early studies in olfaction focused primarily on anatomy and physiology, showing that odors evoke signals from the olfactory sensory neurons in the nose that converge onto the olfactory bulb. Output neurons from the bulb then project directly to olfactory cortical brain regions, making the sense of smell somewhat unique in its anatomical wiring. Our other senses are interpreted by cortical areas of the brain after more extensive neural processing.
Another reason that the sense of smell may have been neglected is that, until recently, experiments into the molecular basis of olfaction have been difficult to conduct.
All that has changed over the last ten years with the cloning of a large family of odorant receptors. Today there is a new cadre of scientists charging into the field of olfactory research. Among them is Leonardo Belluscio, who is conducting research supported by a Career Award in the Biomedical Sciences. He has helped pioneer a new method for actually watching the process of scent recognition as it happens.
Dr. Belluscio did his graduate work on the molecular basis of olfaction with Richard Axel, M.D., of Columbia University.
“I wanted a more complete understanding of the olfactory system in order to better compare it to other sensory systems, and it was clear to me that molecular biology alone would not allow me to do this,” Dr. Belluscio says. “I decided to combine molecular biology with physiology and imaging to allow me to ask more sophisticated questions.”
To do that, Dr. Belluscio chose to pursue postdoctoral work with Lawrence Katz, Ph.D., a Howard Hughes Investigator at Duke University Medical Center. Dr. Katz is well known for his work in visualizing the neural events of the visual cortex, and Dr. Belluscio thought he could adapt some of his techniques to studying the olfactory system.
He spent the first year learning new techniques and applying them to describe the functional organization of the olfactory bulbs of a mouse model. With the BWF Career Award, he decided to focus his interests on studying the mechanisms of learning and memory in the olfactory system.
“The grant allowed me to take on a somewhat riskier project than I might have otherwise,” he said. “It allowed me to gamble a little bit, hoping that it would pay off.”
Dr. Belluscio began his work by creating a map of neural activity in the olfactory bulbs of mice. To do that he used a new technique that allows him to detect olfactory activity by measuring the shift in oxygen-carrying blood toward active nerve sites. Scientists know that blood flow is redirected to areas of intense activity in the brain, so they can correlate activity with blood flow. The technique is gaining acceptance in the olfactory field because it is relatively non-invasive for the animal and gives a comprehensive detailed picture of nerve impulses over the imaged area, Dr. Belluscio says.
He created maps of olfactory nerve activity when mice were presented with a series of odorous molecules called aldehydes, a class of compounds that are highly fragrant and often used in perfumes and other consumer products, and thus were a good choice as model scents for Dr. Belluscio’s work. Thus he created some of the first visual maps of how the brain processes smells, something that has been done only indirectly in the past. His work appears on the cover of the March 15, 2001, issue of the Journal of Neuroscience.
In the paper, he describes how his visual maps correlated well with molecular studies over the last few years:
- Olfactory neurons from each nostril activate symmetrical regions within the two olfactory bulbs.
- Olfactory neurons that respond to structurally similar odorants project to similar locations or are clustered in regions of the olfactory bulbs.
- Patterns of activation within the olfactory bulbs are similar, but not identical among different individuals.
- When a combination of two odorants is presented, the odorant map produced by the bulb is essentially an overlay of the individual odorant maps.
Now that he has laid some of the groundwork for visualizing scent networks in the olfactory system, he wants to continue toward his research goals.
“We think that the experience of smell can be influenced by environment and learning,” says Belluscio. “Our future studies will focus on changes in the olfactory bulb with learning.”
He plans to teach the mice in his studies to associate a specific smell with a reward and see how that combination of scent and memory changes the olfactory map – a first step in understanding the link between scent and memory. Understanding that link has repercussions for more than basic research purposes. Doctors have observed that one of the first clues that a patient has Alzheimer’s disease is a diminished sense of smell. The same is true of Parkinson’s disease and other neural disorders. So an understanding of the neural pathways in smell may shed light on the mechanisms of neural network creation and its subsequent degeneration.
“Studying the sense of smell is a model system to look at learning and memory in one of our most ancient of neural networks,” he says.
Questions for Dr. Leonardo Belluscio:
Name: Leonardo Belluscio, Ph.D.
Title: Postdoctoral Fellow
Recipient: Career Award in Biomedical Sciences
Affiliation: Duke University Medical Center, Department of Neuroscience
How did you first discover you wanted to be a scientist?
As a kid I was always interested in knowing how things work, usually by taking them apart and then trying to put them back together. I suppose to some extent I'm still trying to do that now in the laboratory.
Why did you choose to enter your particular field of study?
I would say it was my experience as a technician at Regeneron Pharmaceuticals that introduced me to the field of neuroscience and sparked my interest in brain research. Later in graduate school I came to appreciate the unique qualities of the mammalian olfactory system and its usefulness as a model system for understanding many neural processes, from system development to modifications like learning and memory to neuronal regeneration.
What has your BWF grant meant for your research?
It has given me a financial advantage in bargaining for jobs, as well as some extra confidence by helping me to establish an independent laboratory in a more timely fashion. Scientifically, the award has provided me a bit of a safety net in case I don't get another grant immediately. Also, it is allowing me to pursue some riskier projects that I would otherwise not consider.
What is the best thing about your job?
The independence. I get to choose the research that I do, the questions I ask, how to address those questions and with whom to address them.
What is your philosophy with respect to your research?
Consider ideas and concepts from other fields, you'll be surprised how often they give insight into your own research. Also, keep an open mind. Realize that the results you get are not always what you would expect and not always the most popular answer.
What kind of advice would you give a scientist just entering academic research?
Know what you are getting yourself into. A lot of time will be spent in the lab doing unsuccessful experiments that tell you very little. Your life will be much happier if you truly enjoy being in the lab doing the science and you're not solely focused on getting results.
What area of science is in most need of new researchers?
Bioinformatics. There is a wealth of data being produced through the many genome projects that needs to be analyzed and understood.
If you had unlimited resources, what one big scientific question would you pursue?
How does the brain encode a memory?
What do you do for fun?
When I have some free time I like to go flying or ride my motorcycle. For vacations I like to go camping or fishing, but mostly I end up doing projects around the house.
What do you plan to do when you retire?
Probably the same things I do now but in different proportions. I also plan to spend more time fishing and maybe even learn to sail.
What is your favorite book?
"The Fountainhead" by Ayn Rand.
-- This story was written by Megan Butler, Communications Intern