Key brain regions talk directly with each other, say Pitt scientists

PITTSBURGH, April 19 – Researchers at the University of Pittsburgh have found new evidence that the basal ganglia and the cerebellum, two important areas in the central nervous system, are linked together to form an integrated functional network. The findings are available online this week in the Proceedings of the National Academy of Sciences.

"The basal ganglia and the cerebellum are two major subcortical structures that receive input from and send output to the cerebral cortex to influence movement and cognition," explained senior author Peter L. Strick, Ph.D., professor of neurobiology and co-director of the Center for the Neural Basis of Cognition, Pitt School of Medicine.

Each subcortical structure houses a unique learning mechanism. Basal ganglia circuits are thought to be involved in reward-driven learning and the gradual formation of habits. In contrast, cerebellar circuits are thought to contribute to more rapid and plastic learning in response to errors in performance.

"In the past, these two learning mechanisms were viewed as entirely separate, and we wondered how signals from the two were integrated," Dr. Strick said. "Using a unique method for revealing chains of synaptically linked neurons, we have demonstrated that the cerebellum and basal ganglia are actually interconnected and communicate with each other."

This result not only has important implications for the normal control of movement and cognition, but it also helps to explain some puzzling findings from patients with basal ganglia disorders.

For example, Parkinson's disease is known to be caused by the degeneration of a specific set of neurons and their synapses in the basal ganglia. However, one of the treatments for the characteristic "resting" tremor of Parkinson's disease is to interrupt signals from the cerebellum to the cerebral cortex. Imaging studies of patients with Parkinson's disease and patients with dystonia, another disorder thought to be of basal ganglia origin, show abnormal increases in activity in the cerebellum.

"Our findings provide a neural basis for these findings," Dr. Strick said. "In essence, the pathways that we have discovered may enable abnormal signals from the basal ganglia to disrupt cerebellar function. The alterations in cerebellar function are likely to contribute to the disabling symptoms of basal ganglia disorders. Thus, a new approach for treating these symptoms might be to attempt to normalize cerebellar activity."

Andreea C. Bostan, a doctoral student in the Center for Neuroscience at the University of Pittsburgh, and Richard P. Dum, Ph.D., Center for the Neural Basis of Cognition, co-authored the paper. The study was funded by the Department of Veterans Affairs and the National Institutes of Health.

As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997 and now ranks fifth in the nation, according to preliminary data for fiscal year 2008. Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see www.medschool.pitt.edu.