From mice to monkeys to humans, ultra-detailed maps of the brain regions that control movement

Before you continue reading, put your hand on your forehead
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You may not think it, but this simple exercise requires the concerted efforts of millions of different neurons in several areas of the brain, followed by signals that move from your brain to the spinal cord at a speed of 200 miles per hour and then move yours.

At the cellular level, rapid movement is a highly complex process.
Like most things involving the human brain, scientists still cannot fully understand how they fit together
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Now, for the first time, neurons and other cells in the brains of humans, mice, and monkeys that control movement have been accurately mapped
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Its creator is a large alliance of neuroscientists united by the National Institutes of Health’s brain research through the advancement of the innovative neurotechnology (Brain) program (Brain).

Today, 17 articles were published in the journal Nature, including a flagship paper describing the entire atlas
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"In the human brain, there are more than 160 billion cells
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Our brain has more than 20 times the population of the world's population," said Dr.

This large-scale collaborative project funded by the BRAIN initiative involves dozens of research teams across the country who have jointly completed a cell-by-cell map of the primary motor cortex

Part of the reason the researchers chose the primary motor cortex is that it is similar in all mammalian species-although the brains of humans, monkeys, and mice are quite different, the way we control movement is very similar because it is new The representative of the cortex, the neocortex is the outermost layer of the mammalian brain.
It not only integrates sensory and motor information, but also produces our complex cognitive functions
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This complete map is a big step in creating a catalog or census of all brain cell types through the Brain Initiative Cell Census Network (BICCN)

Just like the census, the purpose of the cell census is to classify all different types of brain cells, their attributes, relative proportions, and physical addresses, so as to obtain a picture of the cell populations that make up our brain
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Understanding the cellular structure of the "normal" brain is a key step in understanding what goes wrong in the disease

"If we really want to understand how the brain works, we must delve into its basic units
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This is the cell," said Dr.

The creators of the atlas used several different methods to measure various cell attributes, and define a cell type by associating and integrating these attributes.
These attributes include a set of genes turned on by the cell; the "epigenetic" landscape of the cell It defines how genes are regulated; the three-dimensional shape of cells; their electrical properties; and how they connect with other cells
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Single-cell gene expression and epigenetic data are particularly important because researchers can use this data to integrate data from all other types of cells to create a common framework to classify cell types and make comparisons within and between species
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These studies not only require cooperation between researchers to design and execute experiments, but also need to coordinate and share data from the Atlas project and other projects under BICCN
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The Brain Cell Data Center (BCDC) is headquartered at the Allen Institute
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The data center, led by Dr.
Michael Hawrylycz, a brain science researcher at the Allen Institute, helped organize the BICCN alliance and provide a single point of access to research data archiving centers across the country
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"One of our many limitations in developing effective treatments for human brain diseases is that we don't know enough that cells and connections are being affected by a certain disease, so we can't accurately locate them, we need targets," said Dr.
John Ngai , Director of the National Institutes of Health Brain Initiative
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The Allen Institute has played an important role in coordinating the large amounts of data generated by the brain cell survey project, which provides detailed information about the types and characteristics of the cells that make up the brain
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This information will eventually make it possible to develop new therapies for neurological and neuropsychiatric diseases
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Scientists from the Allen Institute for Brain Science participated in 9 of the 17 published studies and led or co-led 6 of them
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The four main studies led by the Allen Institute are as follows:

• How to compare the cell types in the primary motor cortex of mice, humans, and marmosets
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  The research team found that in these three species, most motor cortex brain cell types have similar counterparts, and there are specific differences between species in terms of cell ratio levels, shape and electrical properties, and the opening and closing of individual genes
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  For example, in this area of ​​the brain, human excitatory neurons are approximately twice as large as inhibitory neurons, while mouse excitatory neurons are five times as large as inhibitory neurons
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  The researchers also delved into the famous Betz cells, which are huge neurons that exist in us, monkeys, and many other large mammals, which extend to the spinal cord
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  Researchers also captured known electronic records from human Bezier cells for the first time
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  Mice have evolutionary-related neurons based on a common genetic program, but their shape and electrical properties are very different from humans
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• This is a broader analysis of human brain cell types, focusing on the second and third layers of the six neocortex
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  Compared with rodents, these cortex and the entire neocortex of humans and other primates are much larger and contain more types of cells
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  Researchers at the Allen Institute used a triple technique called Patch-seq to measure the electrical properties, genes, and three-dimensional shapes of several neurons in these layers in tissue samples donated by brain surgery patients
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  This study features these neurons in living human tissues and demonstrates the diversity of neuron types that are specifically used to communicate between different areas of the human cortex, including in-depth research on a type of neuron in Alzheimer’s disease.
  A special type of human neuron that is particularly vulnerable
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• This is the largest collection so far, and a complete whole-brain reconstruction of more than 1,700 different neurons in the rat brain has been carried out
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  Because the axons and dendrites of the cell are long and thin, this three-dimensional neuron tracking method is extensive and complex, but it can obtain important information about the long-distance connections of different types of neurons through axon dendrites to distant brain regions.
  
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  Researchers from the Allen Institute found that the axon trees of these neurons exhibit extremely diverse patterns, some with only a few concentrated branches, while others are spread over large areas
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  For example, in a structure called claustrum, some neurons send axon branches around the entire neocortex in a coronal fashion
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  A typical connection pattern like this is a key attribute used to help distinguish brain cell types
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• The cellular composition of the primary motor cortex of mice, according to the genome opened by each cell ("transcriptome") and the gene regulation modification ("epigenome") on the chromosomes of the cell, approximately 500,000 neurons and other brain cells Cell type classification
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  Using a series of technologies, researchers at the Allen Institute and their collaborators generated 7 types of transcriptomes and two types of epigenome data sets, and then developed computational and statistical methods to integrate these data sets into Shared cell types in the "evolutionary tree"
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  This research has uncovered thousands of marker genes and other DNA sequences that are specific to every cell type
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DOI

10.
1038 / s41586-021-03950-0

A multimodal cell census and atlas of the mammalian primary motor cortex BRAIN Initiative Cell Census Network (BICCN)