Areas of Focus
The goal of the Graybiel Laboratory is to gain an understanding of basal ganglia circuits sufficiently to provide clear potential avenues for therapeutic intervention in neurologic and neuropsychiatric disorders as well as fundamental insights into brain function. The main projects in the lab focus on discovering neural mechanisms underlying habit learning, motivation, motivationally based decision-making, and how these networks translate their signals to the action systems of the brain to build up our behaviors. These studies are paralleled by work on the related issue of how behaviors can be driven first consciously by particular goals and then be transformed into habitual behaviors hardly requiring conscious attention: in essence, how the brain decides which behaviors are successful enough to repeat and eventually make into habits.
These neural functions all deeply involve the striatum of the basal ganglia, a large region in the forebrain whose activity is disturbed in human disorders ranging from Parkinson’s disease to OCD, autism spectrum disorders, depression, stress-related disorders, and addictive behaviors. Dopamine, depleted in Parkinson’s disease, is normally strongly influential on these circuits. So are other neurotransmitters, including serotonin. The entire neocortex plays upon this huge striatal region, suggesting that it is critical to the process of taking cortical commands and reorganizing them and re-weighting them depending on reinforcement contingencies.
To work on these systems, lab members use many state-of-the art methods and engineer mice so that precise biological mechanisms can be addressed. The lab is focused on experiments on the brains of rodents and non-human-primates performing tasks involving reward-based learning, decision-making under conditions of motivational conflict (such as cost-benefit conflict), and other motivational contexts using electrophysiology, optogenetics, chemogenetics, calcium imaging, photometric methods, dopamine-monitoring, immunohistochemistry, along with molecular methods including mouse engineering to detect specific neural populations in neocortex and striatum. The lab is engaged in studying several models of human disease states, including Parkinson’s disease, Huntington’s disease, and obsessive-compulsive disorder and related neuropsychiatric conditions. Finally, the lab works collaboratively with other scientists to match the lab’s tasks to tasks that can be performed by human subjects, including patients; to help engineering projects to improve tools for brain analysis and therapy; and is using anatomical methods based on the research findings to analyze the brains of individuals who suffered from brain disorders. The lab emphasizes data analysis and computational analytic methods to help in interpreting findings.