How bad timing befalls the brain

In patients with Parkinson’s disease (PD), carefully timed actions, such as the coordinated behaviors that make up body movements, can be severely disrupted. The brain’s prefrontal cortex, which is involved in planning behavior, receives input from the ventral tegmental area (VTA), a cluster of neurons in the midbrain that produce the neurotransmitter dopamine. Since dopamine neurons are damaged in PD, a team of Yale scientists wanted to know whether VTA neurons could play a role in temporal dysfunction.

Ralph J. DiLeone, Ph.D., associate professor of psychiatry and neurobiology, and colleagues trained mice to press their noses against a wall for food rewards, which would only be given if at least 20 seconds had elapsed since the last reward. Over time, the mice learned to wait 20 seconds before touching the wall.

As reported in the December 11, 2012 issue of Proceedings of the National Academy of Sciences, when the team precisely targeted dopamine receptors in prefrontal neurons to alter their activity, the mice were much less accurate on the 20-second test—they frequently tried to get a reward after only 10 or 15 seconds. The findings could provide a new target for drugs to help PD patients who have difficulty timing their behaviors.