Using a new molecular genetic technique, scientists have turned procrastinating primates into workaholics by temporarily suppressing a gene in a brain circuit involved in reward learning. Without the gene, the monkeys lost their sense of balance between reward and the work required to get it, say researchers at the National Institute of Mental Health .
"The gene makes a receptor for a key brain messenger chemical, dopamine," explained Barry Richmond, M.D., NIMH Laboratory of Neuropsychology. "The gene knockdown triggered a remarkable transformation in the simian work ethic. Like many of us, monkeys normally slack off initially in working toward a distant goal. They work more efficiently—make fewer errors—as they get closer to being rewarded. But without the dopamine receptor, they consistently stayed on-task and made few errors, because they could no longer learn to use visual cues to predict how their work was going to get them a reward."
Richmond, Zheng Liu, Ph.D., Edward Ginns, M.D., and colleagues, report on their findings in the August 17, 2004 Proceedings of the National Academy of Sciences, published online the week of August 9th.
Richmond's team trained monkeys to release a lever when a spot on a computer screen turned from red to green. The animals knew they had performed the task correctly when the spot turned blue. A visual cue-a gray bar on the screen-got brighter as they progressed through a succession of trials required to get a juice treat. Though never punished, the monkeys couldn't graduate to the next level until they had successfully completed the current trial.
As in a previous study using the same task, the monkeys made progressively fewer errors with each trial as the reward approached, with the fewest occurring during the rewarded trial. Previous studies had also traced the monkeys' ability to associate the visual cues with the reward to the rhinal cortex, which is rich in dopamine. There was also reason to suspect that the dopamine D2 receptor in this area might be critical for reward learning. To find out, the researchers needed a way to temporarily knock it out of action.
Molecular geneticist Ginns, who recently moved from NIMH to the University of Massachusetts, adapted an approach originally used in mice. He fashioned an agent (DNA antisense expression construct) that, when injected directly into the rhinal cortex of four trained monkeys, spawned a kind of decoy molecule which tricked cells there into turning-off D2 expression for several weeks. This depleted the area of D2 receptors, impairing the monkeys' reward learning. For a few months, the monkeys were unable to associate the visual cues with the workload—to learn how many trials needed to be completed to get the reward.