The National Institutes of Health on Thursday announced a detailed map of the basal ganglia, a brain region that helps turn thoughts into actions. Researchers working through the NIH BRAIN Initiative built the atlas, which records the identities, activities and locations of millions of individual cells, according to the agency.
NIH said the work is part of the BRAIN Initiative Cell Atlas Network, a large effort to create baseline maps of the brain at single-cell detail. Researchers could use such maps to pinpoint which cells contribute to disease, the agency said. John Ngai, Ph.D., director of the NIH BRAIN Initiative, said the work is “paving the way toward targeted therapies” for Huntington’s and Parkinson’s disease.
According to NIH, the basal ganglia are a cluster of brain structures that determine how people carry out deliberate physical actions, learn and focus. The team performed single-cell sequencing, a method that reads the genetic activity of individual cells, on donated human brain tissue taken after death. Advanced imaging then tied those cell traits to 3D positions in the brain. The atlases cover neurons and glial cells, a second major group of brain cells, in the mature brain and during early development. They also cover non-human primate, marmoset and mouse brains.
One research group used the human atlas to organize sequencing data from people with autism. NIH said the resulting maps showed possible disruptions in certain cell populations of the striatum, which the agency described as the basal ganglia’s “heavily trafficked intake component.” The agency said standard methods likely would not have found these. Most autism research has focused on the cortex, the brain’s outer layer, and NIH said this study suggests deeper circuits may also be involved.
Another paper built on earlier BRAIN Initiative work that uses genetic switches, called enhancers, to target specific brain cells. Scientists used one enhancer to raise levels of a dopamine precursor in striatum cells in mouse models of Parkinson’s disease. NIH said this targeted approach eased symptoms and reduced the severity of common side effects. The release described results in mice only.
The collection also describes open-source tools. These include a program that prepares data to be compared with the reference atlas and a web-based platform for exploring the basal ganglia without specialized hardware or software. Scientists funded by the network also created the Neuroanatomy-anchored Information Management Platform, which places all studied human brain samples onto a standard 3D brain atlas.
Amy Bany Adams, Ph.D., acting director of the National Institute of Neurological Disorders and Stroke, said NIH expects the publicly available atlases to prompt further discoveries. Andrea Beckel-Mitchener, Ph.D., acting director of the National Institute of Mental Health, pointed to the computing infrastructure the researchers built to support future neuroscience.
The 27 papers appear in the journals Cell, Cell Reports Medicine, Cell Systems, Cell Genomics and Neuron. NIH said it supported the research through the BRAIN Initiative, which the two institutes co-lead. The release did not say how much money the work cost. NIH said the network’s broader goal is to map the entire human brain.