Ann M. Graybiel

Laureate Profile

Ann M. Graybiel, PhD, of the McGovern Institute for Brain Research at the Massachusetts Institute of Technology (MIT), pioneered our understanding of the important role that basal ganglia, a group of nuclei (clusters of neurons) deep within the forebrain, play in a wide range of neurological disorders. At the time she started her research, in the 1970s, most scientists were ignoring that area of the brain. Graybiel, however, persevered. In a groundbreaking experiment, she found that the striatum, the largest nucleus within the basal ganglia, was not a homogenous mass of cells (as was commonly believed at the time). Instead, it had a distinct and sophisticated architecture with column-like modules — dubbed striosomes by Graybiel — that distributed nearly every known neurotransmitter. She also found that striosomes were surrounded by a matrix, which was itself modular. In an extraordinary series of subsequent experiments, Graybiel went on to demonstrate the functionality of this architecture. One of her key findings was that the striosomes projected mainly into the dopamine pathways of the substantia nigra, a basal ganglia structure involved in reward as well as movement. This led her to discover that dopamine-related activity in the striatum undergoes massive reorganization during the learning of new habits — evidence that the striatum plays a key role in behavioral learning. Graybiel and her team also found that changes in striatal neural activity during the learning process lead to the formation of habits, including pathological habits, such as those that characterize obsessive compulsive disorder. More recently, Graybiel has discovered that different families of genes are expressed in striosomes, and that some of those differences are associated with exaggerated compulsive behaviors. Furthermore, using optogenetics, she demonstrated that those behaviors can be manipulated. Graybiel’s groundbreaking contributions to science regarding the architecture and function of basal ganglia have not only deepened our understanding of how the healthy brain works, but have also helped to identify what goes wrong in the brains of people with neurodegenerative and neuropsychiatric disorders, including Parkinson’s disease, Huntington’s disease, Tourette’s syndrome, obsessive compulsive disorder and depression.