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First Comprehensive Census of Cell Types in Brain Area Controlling Movement

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Credit: SciePro/Shutterstock; BRAIN Initiative Cell Census Network, Nature, 2021

The primary motor cortex is the part of the brain that enables most of our skilled movements, whether it’s walking, texting on our phones, strumming a guitar, or even spiking a volleyball. The region remains a major research focus, and that’s why NIH’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative – Cell Census Network (BICCN) has just unveiled two groundbreaking resources: a complete census of cell types present in the mammalian primary motor cortex, along with the first detailed atlas of the region, located along the back of the frontal lobe in humans (purple stripe above).

This remarkably comprehensive work, detailed in a flagship paper and more than a dozen associated articles published in the journal Nature, promises to vastly expand our understanding of the primary motor cortex and how it works to keep us moving [1]. The papers also represent the collaborative efforts of more than 250 BICCN scientists from around the world, teaming up over many years.

Started in 2013, the BRAIN Initiative is an ambitious project with a range of groundbreaking goals, including the creation of an open-access reference atlas that catalogues all of the brain’s many billions of cells. The primary motor cortex was one of the best places to get started on assembling an atlas because it is known to be well conserved across mammalian species, from mouse to human. There’s also a rich body of work to aid understanding of more precise cell-type information.

Taking advantage of recent technological advances in single-cell analysis, the researchers categorized into different types the millions of neurons and other cells in this brain region. They did so on the basis of morphology, or shape, of the cells, as well as their locations and connections to other cells. The researchers went even further to characterize and sort cells based on: their complex patterns of gene expression, the presence or absence of chemical (or epigenetic) marks on their DNA, the way their chromosomes are packaged into chromatin, and their electrical properties.

The new data and analyses offer compelling evidence that neural cells do indeed fall into distinct types, with a high degree of correspondence across their molecular genetic, anatomical, and physiological features. These findings support the notion that neural cells can be classified into molecularly defined types that are also highly conserved or shared across mammalian species.

So, how many cell types are there? While that’s an obvious question, it doesn’t have an easy answer. The number varies depending upon the method used for sorting them. The researchers report that they have identified about 25 classes of cells, including 16 different neuronal classes and nine non-neuronal classes, each composed of multiple subtypes of cells.

These 25 classes were determined by their genetic profiles, their locations, and other characteristics. They also showed up consistently across species and using different experimental approaches, suggesting that they have important roles in the neural circuitry and function of the motor cortex in mammals.

Still, many precise features of the cells don’t fall neatly into these categories. In fact, by focusing on gene expression within single cells of the motor cortex, the researchers identified more potentially important cell subtypes, which fall into roughly 100 different clusters, or distinct groups. As scientists continue to examine this brain region and others using the latest new methods and approaches, it’s likely that the precise number of recognized cell types will continue to grow and evolve a bit.

This resource will now serve as a springboard for future research into the structure and function of the brain, both within and across species. The datasets already have been organized and made publicly available for scientists around the world.

The atlas also now provides a foundation for more in-depth study of cell types in other parts of the mammalian brain. The BICCN is already engaged in an effort to generate a brain-wide cell atlas in the mouse, and is working to expand coverage in the atlas for other parts of the human brain.

The cell census and atlas of the primary motor cortex are important scientific advances with major implications for medicine. Strokes commonly affect this region of the brain, leading to partial or complete paralysis of the opposite side of the body.

By considering how well cell census information aligns across species, scientists also can make more informed choices about the best models to use for deepening our understanding of brain disorders. Ultimately, these efforts and others underway will help to enable precise targeting of specific cell types and to treat a wide range of brain disorders that affect thinking, memory, mood, and movement.

Reference:

[1] A multimodal cell census and atlas of the mammalian primary motor cortex. BRAIN Initiative Cell Census Network (BICCN). Nature. Oct 6, 2021.

Links:

NIH Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative (NIH)

BRAIN Initiative – Cell Census Network (BICCN) (NIH)

NIH Support: National Institute of Mental Health; National Institute of Neurological Disorders and Stroke

5 Comments

  • Roseanne Woo Haltresht says:

    This is a significant milestone for illnesses such as Parkinson’s, where a cure is still elusive. As the wife and caregiver of a Parkinson’s patient, a heartfelt CONGRATS to Dr Collins and the NIH Team! Well done!

  • K Rao says:

    I’m sure under the inspirational leadership of Dr Collins and his dedicated team we would get to see the treatment strategies by precise identification of cells and by treating those cells would solve or at least reduce a broad range of mental disorders in years come.

  • Andrew Goldstein says:

    Incredible progress. I would be interested in learning more about the degree to which each neuronal and non-neuronal cell type can be classified as specialist or generalist. In other words, to what extent can each cell type multi-task versus being confined to very specific activities. Perhaps this would have something to do with brain plasticity?

  • zuccheri gianni says:

    Thanks to Dr. Collins.
    Reading with great interest what this research on cells brings to light, we can glimpse closer prospects of future therapies for severe neurological conditions.
    When we place on the side of the skull a device that generates powerful electromagnetic fields, capable of going beyond the bony walls of the skull that protect the brain, it causes an accelerated stimulation on the evolution paths of the various cells (it could be good or harmful) that was not present in the previous thousands of years?
    Will the use of Transcranial magnetic stimulation, TMS, in the recovery of neurological lesions (also of the motor cortex) have major developments both in research and in daily clinical practice?

    • Zuccheri Gianni says:

      On the other hand, TMS and repetitiveTMS therapy is also employed in neurological damage involving the optic pathways, as indicated in several studies
      (eg Management of toxic optic neuropathy via a combination of Wharton’s jelly-derived mesenchymal stem cells with electromagnetic stimulation), as a hope for those who lose sight.
      What happens if, instead of electromagnetic stimuli controlled with therapeutic tools, the brain is subjected to an avalanche of electromagnetic waves (as in the case of cell phones), several times a day and for several hours?
      Will the growing organism, which has continuous cell replication and differentiation, suffer even more?
      Could these EM waves, along the most traced path within the brain parenchyma, lead to a privileged development of some areas over others, subverting a balance that was firmly pre-established in the genetic evolutionary plans?

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