Neuroscientists roll out first comprehensive atlas of brain cells

When you clicked to read this story, a band of cells across the top of your brain sent signals down your spine and out to your hand to tell the muscles in your index finger to press down with just the right amount of pressure to activate your mouse or track pad.
A slew of new studies now shows that the area of the brain responsible for initiating this action -- the primary motor cortex, which controls movement -- has as many as 116 different types of cells that work together to make this happen.
The 17 studies, appearing online Oct. 6 in the journal Nature, are the result of five years of work by a huge consortium of researchers supported by the National Institutes of Health's Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative to identify the myriad of different cell types in one portion of the brain. It is the first step in a long-term project to generate an atlas of the entire brain to help understand how the neural networks in our head control our body and mind and how they are disrupted in cases of mental and physical problems.
"If you think of the brain as an extremely complex machine, how could we understand it without first breaking it down and knowing the parts?" asked cellular neuroscientist Helen Bateup, a University of California, Berkeley, associate professor of molecular and cell biology and co-author of the flagship paper that synthesizes the results of the other papers. "The first page of any manual of how the brain works should read: Here are all the cellular components, this is how many of them there are, here is where they are located and who they connect to."
Individual researchers have previously identified dozens of cell types based on their shape, size, electrical properties and which genes are expressed in them. The new studies identify about five times more cell types, though many are subtypes of well-known cell types. For example, cells that release specific neurotransmitters, like gamma-aminobutyric acid (GABA) or glutamate, each have more than a dozen subtypes distinguishable from one another by their gene expression and electrical firing patterns.
While the current papers address only the motor cortex, the BRAIN Initiative Cell Census Network (BICCN) -- created in 2017 -- endeavors to map all the different cell types throughout the brain, which consists of more than 160 billion individual cells, both neurons and support cells called glia. The BRAIN Initiative was launched in 2013 by then-President Barack Obama.
"Once we have all those parts defined, we can then go up a level and start to understand how those parts work together, how they form a functional circuit, how that ultimately gives rise to perceptions and behavior and much more complex things," Bateup said.
Together with former UC Berkeley professor John Ngai, Bateup and UC Berkeley colleague Dirk Hockemeyer have already used CRISPR-Cas9 to create mice in which a specific cell type is labeled with a fluorescent marker, allowing them to track the connections these cells make throughout the brain. For the flagship journal paper, the Berkeley team created two strains of "knock-in" reporter mice that provided novel tools for illuminating the connections of the newly identified cell types, she said.