August 2, 2010

Brain Circuits Start and Stop the Action

Scientists identified the neural circuits in mice that signal the start and stop of an action sequence. The finding may advance the understanding of movement disorders and open new avenues of research for their treatment and prevention.

Animal behaviors are, in a sense, sequences of particular actions or movements. The execution of a behavior requires the precise timing and ordering of movements within the sequence. For humans, the proper initiation and termination of action sequences are critical for countless routine behaviors throughout the day, from typing to playing piano to walking. In disorders like Parkinson’s and Huntington's diseases, this ability is seriously compromised.

How we learn and execute behavioral sequences is still largely unknown. Previous studies have found changes in neural activity in the brain’s dorsal striatum and substantia nigra during movement. Dr. Xin Jin, an investigator at NIH’s National Institute on Alcohol Abuse and Alcoholism (NIAAA), and Dr. Rui M. Costa of the Champalimaud Neuroscience Program at the Gulbenkian Institute in Portugal set out to explore the role of these regions in the initiation and termination of newly learned action sequences.

The researchers trained mice to press a lever exactly 8 times to receive a sugar-water reward. As the mice learned this task, the researchers monitored brain cell activity in the animals' dorsal striatum and substantia nigra. Their results appeared in the July 22, 2010, issue of Nature.

The scientists discovered that certain neurons in these regions exhibited a change in activity before the first lever press of a sequence, while other neurons showed a change in activity before the last press of a sequence. These changes in neuron activity emerged as the mice learned how to perform the action sequence to get their rewards.

The researchers next genetically altered mice to disrupt their NMDA receptors, which are known to be involved in learning processes in the striatum. The modified mice could learn to press a lever to get their sugar water. However, the percentage of neurons generating start and stop signals in these mice was significantly lower than in control mice. Tests of the mutant animals' ability to learn the lever-pressing sequence showed that their sequence learning was significantly impaired.

The findings suggest that as we learn new action sequences, certain brain circuits develop activity that signals the beginning and end of each sequence.

"These results could have important implications for disorders where these circuits degenerate, such as Parkinson's and Huntington's disease, in which the initiation and termination of voluntary movement sequences are impaired," Costa says. "More broadly, they are relevant for understanding how we learn and control the execution of behavioral sequences, which may impact disorders of action control like compulsivity."

—by Harrison Wein, Ph.D.