Optogenetic induction of phasic pauses in dopamine signaling in awake, behaving rats
2012 Seed Grant
Mitchell Roitman, Ph.D.
Department of Psychology
University of Illinois Chicago
Why do so many of us struggle with addiction or depression, or both? A BRF grant is helping Mitchell Roitman, Ph.D., look for answers.
“Our work has implications for disorders of reward-directed behavior like overeating that can lead to obesity—which is a huge problem in the United States—or consuming rewards that we shouldn’t, like some drugs.”
Human beings are wired to maximize what benefits us and minimize what harms us. That wiring is somehow crossed in people with diseases like obesity, addiction and depression. Can neuroscience uncover ways to help?
As he tells it, the thrill of learning drew Mitchell Roitman, Ph.D., to research. “I just loved being in the laboratory,” he said. “That’s how I learned best. I got hooked.”
Now Dr. Roitman is hooked on understanding the very reward system that sparked his commitment to research. He’s particularly interested in what drives us to seek harmful rewards, like overeating, drinking too much alcohol, or taking drugs that ultimately become addictive.
Cues and rewards: cause and effect?
Neurologically, Dr. Roitman explained, feelings of reward and reinforcement are triggered by a system that uses dopamine to help the brain send signals. When we sense cues that we associate with feelings of reward, the brain often produces a very brief spike in the level of dopamine.
“We think these dopamine spikes are important in establishing cue-reward associations,” he said. “But it’s still not known whether these are learned associations—bar sign means beer—or whether the associations actually promote behavior—bar sign means beer, bar sign activates dopamine, I go in and get a beer.”
The BRF awarded Dr. Roitman a 2012 seed grant to help him develop a new research tool to study the neurobiology of reward and aversion. The new tool combines highly advanced dopamine measurement, a particular strength of his lab at the University of Illinois at Chicago, with optigenetics.
Optigenetics is a technique that utilizes light and genetics to control the activity of neurons. Dr. Roitman is using optigenetics to install light-sensitive channels in dopamine neurons. Using brief pulses of light, dopamine neurons can be turned on or off to give scientists an opportunity to observe corresponding behaviors. For example, if dopamine neurons are off when an animal sees cues that mean sugar treat, does addictive behavior (consuming the treat) turn off as well?
What happened; what’s next?
Over the year of BRF funding, Dr. Roitman’s team proved the tool works. Specifically, they were able to cause brief pauses in dopamine signaling in an important region of the brain called the nucleus accumbens.
Next, the team will look for causal relationships in animals between brief changes in dopamine concentration and reward and aversion. Using preliminary data from the BRF study, Dr. Roitman has applied for additional funding from the National Institutes of Health to further his research.
Future promise: decoding addiction and depression.
Another aspect of his research relates to loss of reward. Often, Dr. Roitman said, depressed individuals lose the ability to experience pleasure. This is called anhedonia, and may be linked to the absence of dopamine spikes. Using the new research tool, Dr. Roitman will attempt to establish a causal relationship between turning dopamine neurons off and this negative affect.
Developing insights that will contribute to a deeper understanding of the neurobiology that underlies depression. This outcome, combined with the possibility of discovering a path to overcoming addiction, offers truly promising results.