By Anita Srikameswaran
University of Pittsburgh neuroscientists got the green light this week from the Aligning Science Against Parkinson’s (ASAP) initiative to blaze a little-used trail through the brain that might circumvent the missteps caused by Parkinson’s disease.
The research project, “Basal Ganglia Circuits in Parkinson’s disease,” which began in 2021 with a $12 million, three-year ASAP award, leverages the observation that individuals with Parkinson’s disease can move normally under special circumstances, a phenomenon known as paradoxical kinesia, and that symptoms are sometimes alleviated by placebos, said principal investigator Peter L. Strick, Dr. Thomas Detre Professor of Neuroscience and chair of the Department of Neurobiology at Pitt School of Medicine. The project was awarded an additional $8 million this week.
The disease is typically characterized by progressive disability: walking slows, motion stiffens, and hands tremble due to the death of nerve cells in the basal ganglia area of the brain. Yet sometimes during intense emotion, Parkinson’s-affected individuals can easily run from fires or ride a bicycle.
Strick and his team hypothesized that this restoration of normal movement is possible because of a neuronal pathway they call the Open Loop Circuit (OLC), which provides an alternate route from the basal ganglia to the motor cortex to generate movement.
“With our initial ASAP grant, we showed that the OLC exists in monkeys and humans and that the neurons in this circuit provide a motor command signal that can contribute to movement planning and initiation,” he said. “We found also that the OLC remains intact in parkinsonian monkeys.”
During the next two years of the project, the team will determine whether the OLC continues to function in people with Parkinson’s disease with specialized brain imaging studies, see if it can be stimulated in monkeys to restore movement, and examine the molecular signatures of circuit neurons. If successful, they will test whether activating the OLC with deep brain stimulation can provide new therapies.
Exploring neural circuitry could lead to discoveries of great impact, said Strick, who pioneered brain mapping. “What we know about brain connections right now is just the tip of the iceberg,” he said. “We learn something new from every experiment we do, something fundamental about how the brain works.”
The team includes Professor Robert Turner, Assistant Professor William R. Stauffer and Research Assistant Professor Andreea Bostan, Department of Neurobiology, School of Medicine, and Helen Schwerdt, assistant professor of bioengineering, Swanson School of Engineering, all from Pitt; and neuroscientist-clinician Scott Grafton of the University of California, Santa Barbara.
ASAP is a coordinated research initiative to advance targeted basic research for Parkinson’s disease. Its mission is to accelerate the pace of discovery and inform the path to a cure through collaboration, research-enabling resources, and data sharing. The Michael J. Fox Foundation for Parkinson’s Research is ASAP’s implementation partner and issued the grant.
Photo by Annie O’Neill