NIH BRAIN Initiative debuts cell census of mouse motor cortex – for starters

Researchers also identify mouse brain cells for mating, parenting, aggression.

The same cluster of neurons (inside the blue square at upper right) is preferentially activated in virgin females, mothers and fathers displaying parenting behavior when exposed to mouse pups. Drs. Catherine Dulac, Xiaowei Zhuang, and colleagues, Harvard University

Researchers funded by the National Institutes of Health have reached a milestone in their quest to catalog the brain’s “parts list.” The NIH BRAIN Initiative Cell Census Network (BICCN) has issued its first data release. Posted on a public web portal(link is external) for researchers, it profiles molecular identities of more than 1.3 million mouse brain cells and anatomical data from 300 mouse brains – among the largest such characterizations to date.

BICCN research teams(link is external) focused initially on a key area of the mouse motor cortex, an area of the brain that controls movement, as a first major step in the 5-year effort. Initiated in 2017, the BICCN projects aim to build comprehensive, three-dimensional common reference brain atlases that will ultimately integrate molecular, anatomical and functional data on cell types in mouse, human and non-human primate brains. To expedite scientific impact, they are making their data immediately available to the research community via the web portal.

“No single research group could do this by themselves—they needed to leverage the power of a team,” explained Joshua Gordon, M.D., Ph.D., director of the National Institute of Mental Health (NIMH), which is helping to coordinate the BRAIN Initiative effort. “The BICCN is a product of nine different teams each bringing to bear their finely-honed tools to the same brain region at the same time. By doing so, they could compare results and create a unified resource for the community.”

Molecular fingerprints

The new molecular fingerprints cover comprehensive information on gene transcription and epigenomic signature maps of the brain cells. Each type of cell is classified according to its molecular characteristics and identifiable by telltale marker genes.

“We are witnessing an unprecedented and accelerated evolution of technologies that permit molecular fingerprinting of individual cells,” noted Andrea Beckel-Mitchener, Ph.D., chief of Functional Neurogenomics Program at NIMH. “The BICCN projects enable new studies in the wider scientific community by providing novel tools and data to understand basic biology and disease conditions at the cellular level. Over the next few years, we expect similar data from millions of human cells that will help us understand what goes awry in human brain disorders.”

“We are proud to be a key part of this initiative, both as a developer of the cell types atlas and as the home for the Brain Cell Data Center (BCDC), which is designed to bring these data, tools and knowledge to the public,” added Michael Hawrylycz, Ph.D.,(link is external)Investigator at the Allen Institute for Brain Science, Seattle, Washington, one of the participating teams.

Mating, parenting, aggression

In a related development, NIH-funded researchers just announced the discovery of cellular secrets of key social behaviors – mating, parenting, and aggression – in the brains of mice, by combining a new imaging-based method of single cell analysis with a more established single cell gene sequencing method.

The ability of the imaging-based method to be used in intact tissue made it possible, for the first time, to pinpoint specific populations and gene expression characteristics of cells involved in the social behaviors. This is just one of the findings emerging from a new cell atlas of the mouse hypothalamus preoptic region, which is known to mediate key social behaviors and homeostatic functions, such as sleep, thirst, and thermoregulation. The atlas mapped cells’ spatial organization, profiled gene expression, and identified activity markers.

In work that shows why cell types matter, Drs. Catherine Dulac(link is external), Xiaowei Zhuang(link is external), of Harvard University, Cambridge, Massachusetts, and colleagues, report on specific mouse cells involved in social behaviors in the November 1, 2018 issue of the journal Science.

The new evidence suggests that circuits comprised of neuron types with distinct gene expression signatures control such behaviors and functions. Distinct cell clusters in the brain were active in mating, parenting, and aggression. Depending on the behavior, telltale cell activity signatures characterized virgin females, aggressive virgin males and males that fathered mouse pups. In each case, the activated neurons tended to be of the type that reduce circuit activity. This line of research holds promise for unraveling how different brain cell types communicate to form functioning circuits and how this process may be disrupted in certain brain disorders, say researchers.

Grants: MH113094, MH111502, HD082131, HD092542, EY028625

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

About the National Institute of Mental Health (NIMH): The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

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