Brain atlas unveils dozens of cell types that control movement and could inspire targets in neurological disease

When the National Institutes of Health launched the BRAIN Initiative in 2013, its ambitious goal was to bring together federal agencies, research organizations, academics and companies to improve the world’s understanding of the human neurological system. Now a team of participants led by the University of California, Berkeley, has made a major contribution to that effort.

The Berkeley-led team discovered that the primary motor cortex in the brain, which controls movement, houses up to 116 distinct cells—five times more than had been identified in previous research. They described their findings in 17 studies published in the journal Nature.

The research is part of a substudy called the BRAIN Initiative Census Cell Network (BICCN), which was created in 2017 with the goal of mapping all of the neurons and glia—support cells—in the brain. The scientists used several technologies to characterize brain cells, including single-cell RNA sequencing (scRNA-seq), which measures the levels of messenger RNA in each cell. They also measured gene expression, connectivity and shape. They profiled brain cells from people, mice and marmosets.

“The big advance by the BICCN is that we combined many different ways of defining a cell type and integrated them to come up with a consensus taxonomy,” said co-author and Berkeley assistant professor Dirk Hockemeyer, Ph.D., in a statement. “So, now we can say this particular cell type expresses these genes, has this morphology, has these physiological properties, and is located in this particular region of the cortex. So, you have a much deeper, granular understanding of what that cell type is and its basic properties.”

Among the findings was that humans have double the amount of distinct inhibitory neurons than excitatory neurons in the primary motor cortex. Mice, by contrast, have five times as many different types of inhibitory neurons.

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The BRAIN Initiative has recruited some of the biggest names in the private and public sectors, including General Electric, GlaxoSmithKline, the National Science Foundation and more. In 2019, Abbott signed on to contribute neuromodulation technology to the research. Google was an early participant, teaming up with the Allen Institute for Brain Science to provide the infrastructure to house the huge datasets generated by the effort.

The Allen Institute, funded by the late Microsoft co-founder, is contributing to the push to better characterize the brain. In 2019, the group published a study of 75 different cell types in brain samples donated by epilepsy patients, describing key differences between how excitatory and inhibitory cells act in the human brain versus the mouse brain. They said the findings could inspire better models for studying brain diseases and ultimately novel treatments.

The Berkeley-led team believes the new study is a key step towards building a complete cell atlas of the brain. “This body of work provides a roadmap for exploring cellular diversity and organization across brain regions, organ systems and species,” they wrote in the study.