In humans, throwing a ball, typing on a keyboard, or engaging in most other physical activities involves the coordination of numerous discrete movements that are organized as action sequences. Scientists at the National Institutes of Health and the Gulbenkian Institute in Portugal have identified brain activity in mice that can signal the initiation and termination of newly learned action sequences. Findings published in online issue of Nature.

"This interesting report should advance our understanding of the neurobiology of movement disorders, and open new avenues of research for their treatment and prevention," says Kenneth R Warren, acting director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the NIH.

The study was conducted by Xin Jin, an investigator in the NIAAA Laboratory for Integrative Neuroscience, and Rui M Costa, principal investigator of the Champalimaud Neuroscience Programme at the Gulbenkian Institute. The researchers trained mice to press a lever exactly eight times to receive a sugar-water reward. As the mice learned this task, the researchers monitored brain cell activity in the animals' basal ganglia, deep brain structures that are known to help start and control movement.

"We recorded activity in the dorsal striatum and substantia nigra during the learning of novel action sequences," explained Dr Jin. "Although previous studies have reported changes in neural activity in these areas during movement, their role in the initiation and termination of newly learned action sequences has not been explored."

Dr Costa and Dr Jin 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. They also noticed that this activity signalling the initiation and termination of each action sequence emerged during learning.

The researchers then evaluated these circuits in mice that had been genetically manipulated to disrupt the development of the start and stop signals. The researchers found the manipulation had impaired the learning of the lever-pressing sequence.

"Our findings demonstrate that as we learn novel action sequences, these basal ganglia circuits develop activity that signals the beginning and end of each sequence," says Dr Costa. "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. 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."

The National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health, is the primary US agency for conducting and supporting research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems. NIAAA also disseminates research findings to general, professional, and academic audiences.