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Mapping the mammalian motor cortex

A top down and side view of where neurons in one layer of the cortex project around the brain. Peng et al, Nature 598, 174–181 (2021)

The human brain is an incredibly complex organ. It’s made up of about 90-100 billion nerve cells, or neurons, along with roughly the same number of other cells. There are trillions of neuronal connections in the brain, and each person’s brain is unique. How your brain develops and functions depend on many factors, including your genetics and the environments you grew up in. Understanding the differences in people’s brains may help scientists better understand mental health and diseases, such as schizophrenia, addiction, seizure disorders, and Alzheimer’s disease.

To develop a comprehensive reference catalogue of all the cell types in the brain, NIH’s ) brought together more than 250 scientists at more than 45 institutions across three continents for a coordinated mapping effort. The group started by mapping the locations, molecular profiles, and functions of all of the cells in one brain region: the motor cortex. The motor cortex is responsible for directing complex body movements and is known to have a similar role across mammalian species. The researchers compared the cells in this brain region across three species: humans, monkeys, and mice. Their results were published in a series of 17 papers in the journal Nature on October 6, 2021.

In the flagship paper, the researchers gave an overview of the reference atlas. Based on experiments with millions of cells, they described a cross-species, data-driven framework of brain cell types in the motor cortex. They characterized the cell types and traced neural circuits using a variety of diverse approaches.

The effort revealed that motor cortex cells could be organized in a hierarchy of families and classes. At the highest level, the researchers identified 25 general cell types—16 neuronal and nine non-neuronal—that were distinct and conserved across the three species. But the team also found important differences in gene expression between species that may account for variation in the way these three species process neural information. The cell types in the human brain, for example, showed more diversity.

The group also created a wiring diagram of the motor cortex by tracing where the defined cell types project to and from in the brain. Most of the cells formed a complicated network, with multiple connections in different brain areas.

In addition, the team developed genetic tools to precisely monitor and modulate the neural activity of specific cell types. These tools will be useful for future studies to parse out the roles of the different cell types.

“This work represents a crucial step that will dramatically enhance the pace of advances in understanding the brain,” says Dr. Joshua Gordon, director of NIH’s National Institute of Mental Health (NIMH).

“Thanks to this groundbreaking collaboration, we now have a comprehensive understanding of the brain cells found in the motor cortex of the brain and their basic functional properties,” says NIH Director Dr. Francis S. Collins. “The atlas will provide a springboard for future research into the structure and function of the brain within and across species.”