Roger Nicoll, MD, still remembers the two books that changed his life. One, was discovering the drawings of "the beautiful structure of neurons" by Nobel laureate Santiago Ramón y Cajal. Nicoll was convinced that the different kinds of brain cells Cajal described must have different functions. Then came the book by Nobel laureate John Carew Eccles describing the use of electrodes to record impulses from individual neurons. Nicoll, a first-year medical student, was instantly captivated by the potential of Eccles' technique to reveal the functions of the types of neurons he saw in Cajal's drawings.

"I decided to take a year off to learn this technique," recalls Nicoll, now a professor of cellular and molecular pharmacology at UCSF. "I was hooked. I went back and finished medical school and I've been doing exactly what was in that book for the rest of my life."

According to his colleagues, he is the world's expert on how the connections between neurons become stronger with use over time, called synaptic plasticity. This has potentially profound implications because researchers believe that synaptic plasticity is the mechanism behind learning and memory. This means that Nicoll is arguably poised to solve one of science's greatest mysteries: the mechanism that allows the human brain to process, store and recall information.

Nicoll will be among the first group of researchers moving to the new Mission Bay campus in 2003. In his new space, Nicoll will be closer to those colleagues he now collaborates with and ones with whom he has long been interested in establishing connections. "My own research is going to be very positively affected by the move."

When he's not studying the brain, Nicoll does "things to distract my mind." He enjoys playing tennis year round. During the winter, he skis and, during the summer, he windsurfs regularly on the weekends. "On Monday, I come in and I'm pretty much beaten up and ready to switch from physical to mental activity."

A New Jersey native, Nicoll developed his interest in the nervous system while an undergraduate at Lawrence University in Wisconsin. He recalls classes in comparative biology that delved deeply into classical evolution, including evolution of the brain.

"What stood out to me was that, as organisms became more complicated, the organ that had to be the most sophisticated was the nervous system. The crowning achievement in evolution is the human brain. That fascinated me."

Once at the University of Rochester Medical School , Nicoll tried to find ways of studying such a complex structure. "It was kind of a black box." He flirted with various careers, from neurology to neurosurgery. But, he became disenchanted with approaches that seemed too crude.

Then came the book by Eccles. After a year at the National Institutes of Health, Nicoll's future in academic research, in general, and electrophysiology, in particular, was set.

He has focused much of his career on synaptic plasticity. His findings have gone a long way toward resolving controversy in that field. "For a long period of time, the field was hung up in a debate. Nobody could agree on whether the persistent change resided in the presynaptic or postsynaptic side" of the connections between neurons.

Based on a variety of experiments done by Nicoll and his colleagues, most researchers agree that the post-synaptic side of the synapse is where the important changes are taking place. Nicoll's work has also shown that the increasing strength of electrical current at the synapse is due to the movement of current-regulating ion channels from inside the cell to its surface.

These new findings meant Nicoll had to learn a new field, something he finds exciting but daunting. "I'm not the least bit the molecular biologist," he admits. But, in hopes of continuing to unravel the secrets of synaptic plasticity, Nicoll now collaborates closely with UCSF's Mark von Zastrow, PhD, associate professor of psychiatry, and David Bredt, MD, PhD, professor of physiology, among others.

Bredt studies the workings of ion channels -- proteins imbedded in the cell membrane of neurons at the synapse that regulate the flow of ions across the membrane. Bredt says Nicoll's use of electrophysiology to deduce the movement of ion channels changed the course of the field.

"That was a major breakthrough in the last five years," Bredt said. The two are now working together to expand on these findings using molecular biology techniques. Their working hypothesis is that memory reflects changes in the number of the cell-surface molecules they are studying.

In addition to advancing his field, Nicoll has made some unexpected and intriguing discoveries. For example, he found a novel signaling pathway in the brain that uses endocannabinoids, substances made by neurons that act on the same receptors as marijuana. "What is so exciting about this is that virtually all of the behavioral effects of marijuana are due to its action on this one type of receptor. Since we now have a pretty good idea of what this receptor does at the cellular level, marijuana provides a remarkable tool to try to bridge the gap between receptors and molecules in the brain and complex behavior," Nicoll says.

Bredt says that despite Nicoll's stature in the field, he remains an accessible teacher and colleague, "People always assume he has a big operation, but he maintains a small lab. He's always available and you know he's there if his briefcase is there. His door is always open." Bredt also describes Nicoll as a remarkably dedicated and creative scientist who has trained the world's top electrophysiologists. "He manages to stay ahead of them," he says. "After 40 years in the field, his focus is at least as great as it ever was and that's quite inspiring."

Nicoll credits the amazingly complex human brain with holding his attention for four decades. "I've been looking at the individual building blocks of the brain and how they are put together. I haven't really wavered at all since my first year in medical school. And, there's at least another hundred years worth of work left to be done."

Source: Camille Mojica Rey

Last updated February 7, 2006

Roger Nicoll

Scientist Roger Nicoll, MD, holds the two books that changed his life. One, by Santiago Ramón y Cajal contained "the beautiful structure of neurons," and the other book by Nobel laureate John Carew Eccles described the use of electrodes to record impulses from individual neurons.

QB3 building

Roger Nicoll, professor of cellular and molecular pharmacology at UCSF, talks to neuroscience graduate student Kaiwen Kam about an experiment that involves recording electricity from brain cells. Photos by Christine Jegan.