In 2003, Geoff Schoenbaum left his mentor's lab.
He had a Ph.D., an M.D. degree, a new son, his first assistant professorship and nearly $1.3 million in grants to continue brain research developed during his association with Michela Gallagher, a world-class neuroscientist at the Johns Hopkins University.
It was, one might say, a very special time, the year a young scientist found himself squarely astride the shoulders of giants.
His latest work, featured as the cover article the Aug. 28 edition of the journal Neuron, described how one part of the brain, the amygdala, controls representations made in another, the orbitofrontal cortex.
The idea explored was as old as Pavlov's dog: Learning occurs by forming associations between theoretical constructs that represent objects and events, and then those associations guide behavior -- as with Pavlov's hound, where the dog heard a bell, thought of food and salivated. Schoenbaum, in collaboration with Gallagher and others, identified one of the physical networks in rodents' brains that allows such learning to occur.
As the new year approachess, he has begun hiring assistants for his own lab at the University of Maryland School of Medicine. He is ramping up for a five-year study that could be particularly relevant to the teeming life outside the windows of his new office in downtown Baltimore: the neurobiology of drug abuse and addiction.
The focus remains on the brain circuits that he and Gallagher had already started to investigate. He will still rely on rats to illuminate his interests. But the idea that propels his quest has implications that could reverberate far beyond the lab.
The questions he will ask are ones that "haunt any consideration of drug addiction," according to Nora D. Volkow, director of the National Institute on Drug Abuse, which is funding the research.
Why do people addicted to drugs compulsively seek and use drugs, even after the drugs no longer provide pleasure? Why do addicts risk health and well-being to obtain drugs even when they know better?
The answer may be in the brain circuits Schoenbaum has begun to map.
"We think addiction might reflect a disregulation of behavior controlled by this brain system. We know, for example, that if you give rats addicting drugs for weeks, they create long-lasting changes in their brain systems. The drugs change neuro-transmitter levels. They change receptor levels. They even cause structural change that you can see when you cut the tissue up and put it under a microscope -- changes in the branching patterns of the cells, changes in the number of contacts between neurons.
"So the new research asks the question, 'If we give rats a regular course of cocaine and test them on behavioral tasks that are critically dependent on these brain areas, do we see compulsive behaviors that correspond to changes in this circuit? And once we've done that, we'll ask, how can we fix it?"
Why this interest in addiction?
Besides its scientific importance, Schoenbaum acknowledges the social implications have a more personal significance.
"When I first moved to Baltimore, the book The Corner came out, and I read it, and it had a really big effect on me," he says. "The writers did a tremendous job conveying what it's like to be an addict. It's not a moral problem or a problem of willpower -- that's not the issue. Drug addiction leads to a dramatic number of social problems.
"I mean, if you could change addiction, Baltimore would be a different place, right?"