Principal Investigator Ann Graybiel
The core function of the basal ganglia, in Graybiel’s view, is the type of learning that leads to the formation of habits -- sequences of behavior that are learned to the point where they become automatic. Many everyday motor actions become habitual through repetition, but we also develop habits of thought and emotion. If cognitive and emotional habits are also controlled by the basal ganglia, this may explain how damage to these structures can lead not only to movement disorders but also to repetitive and intrusive thoughts, emotions and desires.
Graybiel’s team uses electrical recordings, behavioral tests and gene-based approaches to study these issues. They recently demonstrated dramatic changes in neural activity in the striatum as animals learned new habits, and found that these changes are coordinated with activity patterns in the hippocampus, a brain structure involved in memory of facts and events. Along with her clinical collaborators, Graybiel has discovered that the functional subdivisions that she previously identified in the striatum are disproportionately vulnerable in Huntington’s disease and in models of Parkinson’s disease and dopa-responsive dystonia. She is currently focusing on new methods for influencing striatal activity, and on novel genes that her group has discovered in this brain region. These genes appear to be critical for the brain’s response to drugs of abuse and to L-dopa, a major therapeutic drug for Parkinson’s disease. Graybiel is exploring the potential of these genes for therapeutic drug development.