Jay Baraban of Neuroscience
on learning how drug abuse rewires the brain:
What do you study?
BARABAN: We are trying to understand how the brain adapts to a constantly changing environment. We look at the level of synapses—the microscopic connections between neurons in the brain—and investigate synaptic plasticity: how neurons change their connectivity and communication with each other.
More specifically, we look at the changes in synaptic function caused by drug abuse. We’re investigating why exposure to a single molecule—cocaine, or morphine—can cause very long-lasting changes in behavior. It’s as if taking cocaine creates some sort of chemical memory, so you will seek the drug at the expense of other things in your life. Even once you’re off the drug, you’ll have cravings for it if you are exposed to stimuli that remind you of the drug. We’re trying to understand the molecular mechanisms that control those cravings—how does the desire for the drug get written into the brain, and how can it be erased?
And what have you learned?
BARABAN: Studies focusing on a protein called Narp discovered by Paul Worley’s lab, also in the Neuroscience department at Hopkins, have provided important clues to understanding the type of synaptic plasticity that mediates drug craving. Narp is released at synapses located in parts of the brain that regulate craving and appears to control the ability of these synapses to adapt to changes in the environment.
How does Narp affect behavior?
BARABAN: Studies conducted by Irving Reti when he was a postdoc in my lab in collaboration with Peter Holland of Psychiatry have looked at how the presence of Narp affects mouse behavior. If a mouse gets an injection of morphine on one side of the cage, it will spend more time on that side of the cage. Later, if you stop giving morphine on that side of the cage, mice with normal levels of Narp will eventually stop hanging out there. But mice that do not have Narp will continue to prefer going to that side of the cage. They don’t seem to be able to erase their association of that side of the cage with getting morphine. In other words, not having Narp seems to make the mice more prone to addiction-like behaviors.
How did you get into research?
BARABAN: My background is in psychiatry. I did my psychiatry rotation in medical school at Yale on a research ward where they were testing new treatments, which was really exciting. They were bringing in patients to study new medications and understand the basis of diseases. On the ward, they tried to translate advances made in animal models in the lab, where I did my Ph.D. research, to improving patient care. It taught me that basic research on the neurobiology of behavior is critical for really making progress in understanding what happens in psychiatric disorders and developing new treatments.
--Interviewed by Vanessa McMains, written by Sarah Lewin
Jay Baraban on how neurons encode messages in the brain: