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Rae Silver and the rhythm of life

Neuroscientist Rae Silver retrieves brain tissue from storage in a -80 Celcius freezer. Silver has made significant contributions to our understanding of animal behavior through Circadian rhythms. (Photo: Rae Silver)

On an early evening in December, Rae Silver sits at her desk, facing two computer screens and clutching a cup of coffee. "It's very handy to have text and figures on separate screens," she says, using her mouse to double-click through various files on her computer. Pictures of real mice and their fluorescent brain scans flicker on and off the screens as she skims PowerPoint presentations. She is searching for the right visual aids to explain her career's obsession, which is at once intuitive and confounding: Circadian rhythms, or how our bodies and behaviors change in patterns over a 24-hour period.

Silver is a neuroscientist, with joint appointments at Columbia University and Barnard College. In Morningside Heights, she leads the Silver Neurobiology Laboratory in examining how, at a molecular and cellular level, Circadian rhythms regulate our day-to-day life physiology and behaviors — from how we experience jet lag to how we metabolize drugs. As relatable as these rhythms are, Silver is quick to point out there is still so much we don't know about how they work.

A notification box pops up in her right-hand computer screen. "Ha! I've been waiting for this all day," she says, and halts her PowerPoint search to contemplate the 3D computer-generated geometric shapes embedded in the e-mail.

In the comforts of her office — Grateful Dead CDs piled on the floor, bag of chocolate nearby, photographs of her children and colleagues on walls around her — Silver seems a world away from her lab one floor below in the basement, where nearly a dozen researchers hover over mouse cages, microscopes, and high-tech equipment to analyze mouse brain behavior. But as she analyzes the 3D shapes, and explains what they are, it becomes clear that her lab is here in her office, too. It's always been with her.

Growing up in Montreal, Silver was inherently interested in human behavior. She didn't understand, for example, how during brutally cold winters, some people walked around in short skirts or without coats. "I always wore a snowsuit in winter because it was freezing cold," she said. A minor observation, perhaps, but it got her thinking: Why do people behave in certain ways? Variations of this question led her to study psychology and physiology at McGill University and biopsychology at the City University of New York, and ultimately to earn her Ph.D. in biopsychology at Rutgers, where she first learned the significance of Circadian rhythms working with ringdoves under famed ethologist Danny Lehrman.

In these birds, she observed that mother and father bird split the daylight hours laying on their eggs and caring for their young, and therefore, must have internal sensitivity to timing. Silver learned that scientists had identified a tiny area in the brain of mammals, called the suprachiasmatic nucleus (SCN), that seemed to be a "master clock\ controlling this Circadian behavior. She wanted to test this hypothesis, and the SCN quickly became the focus of Silver's impressive career.

In the past 30 years, Silver has made significant contributions to our understanding of animal behavior through Circadian rhythms: She has identified the pathway by which light travels from the eye to the SCN and resets the "master clock.\" She has also discovered how to transplant successfully the SCN from one animal to another. Yet when Silver is alone brushing her teeth, she's thinking about what work there is left to do. These days, her focus is on mapping how the nearly 20,000 neurons work together in the SCN to control Circadian rhythms. We know that this biological clock exists and regulates behaviors, but Silver wants to know just how, precisely, does it work? Each neuron in the SCN has its own gene clock, and synchronizes with all of the other gene clocks, to create the "master clock" that regulates behavior. But the process of this synchronization remains unknown.

Silver has a keen sense of humor about her obsessive focus on the SCN, and understands that some people may ask, why are you spending your life on this circuit? "I too would like to explain consciousness, but I don't think we're near being able to do that," she said. "What we can try to understand is how complicated properties emerge from the operation of individual cells working together."

While the SCN occupies much of her thought, Silver also oversees other brain research in her lab including that of mast cells, which she calls "funny" brain cells because they typically have to do with the immune system. She is curious as to what role they have in the brain.

"Rae Silver has an amazing ability to take large and complicated issues and, using her critical intelligence, boil them down into sets of clear questions," said Donald Pfaff, a neurobiologist at Rockefeller University who has collaborated with Silver for the past four years. From speaking with her, it is clear Silver has a way of making the most abstruse scientific concepts accessible, if not compelling. In her world, neurons are like children who play tag and swing on swings in the playground.

The geometric 3D shapes on Silver's computer that so excited her are visual models for how the neurons synchronize in the SCN. Her colleague and friend, Duncan Foley, an economist and professor at the New School for Social Research sent them. Together with Duncan's son, Niko, a Ph.D. candidate in neuroscience, the two are trying to demystify the SCN one neuron connection at a time. It's a challenging puzzle to solve, Silver concedes, but puzzles are what got her interested in the brain to begin with. "If it were just about reflexes, it would be boring!"