Oct 7, 2021 - Science

Scientists map a key circuit of cells in the brain

Complete, brain-wide reconstructions of several different types of mouse neurons showing their position in a rendering of the mouse brain.

Reconstructions of several different types of mouse neurons showing their position in the mouse brain. Credit: Allen Institute

Scientists have created a catalog of the cells in the brain's movement control center — a first step toward deciphering the circuits of the brain's nearly 90 billion neurons that underpin our movements, thoughts and emotions.

Why it matters: Cells don't operate in isolation. Determining the circuits that connect neurons could help researchers understand processes in the brain and what happens when they go awry from disease.

  • Ultimately, the hope is these brain maps will provide new targets for drugs to treat Alzheimer's and Parkinson's diseases, as well as neuropsychiatric diseases where there is an aberration in the way cells communicate, says John Ngai, director of the NIH's BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative, which coordinated the effort to create a cell census.
  • Ngai and others envision treatments that act on specific cell circuits that give rise to disease rather than every cell. Such targeted treatments could help reduce the side effects seen with some drugs.

Driving the news: Hundreds of researchers collaborated to define and catalog the cells in the primary motor cortex region of the brains of mice, marmosets and humans, they report this week in 17 papers in the journal Nature.

  • The goal of the research is to generate a "parts list for the brain," says Hongkui Zeng, director of the Allen Institute for Brain Science and co-author of some of the papers.
  • There are close to 170 billion cells in the brain (about half are neurons and half are other cells) with trillions of connections between them. Some cells can have similar shapes but differ in their functions and locations.
  • Researchers have struggled to place cells into distinct groups, which would help them figure out the circuits they form and how they function.

What they did: The researchers combined information about the genes being expressed in cells (their transcriptome), their shape, electrical activity and other properties and found more than 100 types of cells in the human motor cortex.

  • Comparing the RNA information with the shape, electrical activity and other properties of cells, the researchers found that RNA patterns can be used to predict a cell's type.
  • They then determined where classes of cells were located within the motor cortex, which is involved in coordinating movement.
  • When the cells from the mouse motor cortex were compared to those in marmosets and humans, they found some key differences between how the cells are organized. But many of the same cells were present in the three species, suggesting those cells are central to the circuits in mammals more broadly and pointing to possible animal models for studying diseases.

Yes, but: A map of the entire human brain circuitry is still far in the future.

  • "Getting a parts list is really only the first step," Zeng says. "We don’t know what the cell types do yet and how they are connected with one another."
  • There's also the issue of how cell circuits vary between individuals and how they change, whether subtly with time or dramatically during development or disease, she says.
  • And there is the sheer size of the human brain: It is 2000 times larger than a mouse brain. "It could take two years to do the whole mouse brain," Zeng says, adding there is a need for tools to speed the process. "We don't want to take 1,000 years to do the human brain."

The big picture: The research published this week is one effort among many chasing a grand goal to map every cell in the human body.

  • It centers around a new frontier in biology — the study of where different cells are located in tissues and how they interact and influence one another.
  • That spatial information gets scientists to the "ground truth" of the biology, says Ben Hindson, chief scientific officer at 10X Genomics, a company that sells tools for analyzing properties of cells within tissues.
  • Spatial biology is being used to study cancer diagnostics, immune responses to cancer therapies, regenerative medicine and more, says Evan Keller, a cancer biologist at the University of Michigan, Ann Arbor, who directs a single cell spatial analysis program at the university.
  • "It's going to help us clinically in terms of diagnosis, prognosis and precision medicine," he predicts.

Editor's note: This story was corrected to note that the human brain is 2,000 times, not 200 times, larger than a mouse brain.

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