UF neuroscientists including Habibeh Khoshbouei have found that well before symptoms of Parkinson’s disease appear, activity of dopamine neurons in the substantia nigra is already altered. The team used electrophysiology, histology, and high-speed calcium imaging to map real-time network connectivity. They found that while the protein a-synuclein disrupts dopamine-producing cells in that region, they remain mostly intact in the nearby ventral tegmental area.

Parkinson’s symptoms typically begin after a significant loss of dopamine neurons in the substantia nigra. “Understanding the earliest functional breakdown of dopamine neurons helps us design drugs or gene therapies aimed at restoring healthy firing patterns and network connectivity before irreversible damage occurs,” says Khoshbouei. The team will next focus on understanding how long it takes for stressed networks in the substantia nigra to degenerate. They also plan to analyze side-by-side comparisons of the substantia nigra and ventral tegmental areas.

• Habibeh Khoshbouei