An Atlas of the Motor Cortex Makes Its Debut

The power of scientific collaboration was front and center in October, when a consortium of researchers spanning three continents published an atlas of the primary motor cortex — the brain region that guides movement — in mice. Together, the researchers analyzed millions of cells to determine their molecular identify, classify their type and situate them in the brain’s complex architecture. The data they have generated will serve as a foundational resource for neuroscientists worldwide — and move the field toward even more ambitious projects, such as complete 3D atlases of the mouse or human brain. Learn more about this milestone and other new discoveries from researchers affiliated with the Kavli Neuroscience Institutes.

Neuroscience hits a major milestone

On October 6, more than 250 scientists working as part of the BRAIN Initiative Cell Census Network (BICCN) published a trove of data describing the mammalian brain in unprecedented detail. The special collection, consisting of 17 research articles, provides an atlas of cell types and a neuronal wiring diagram of the primary motor cortex of the mouse, along with comparable data from the monkey and human. Among the lead authors were several researchers affiliated with the Kavli Neuroscience Institutes, including:

• Eran Mukamel, an advisory board member of the Kavli Institute for Brain and Mind (KIBM) at the University of California, San Diego. Mukamel’s team analyzed more than 500,000 cells to create a multimodal atlas of 56 neuronal cell types in the mouse primary motor cortex.

• Edward Callaway, Co-director of KIBM and a professor at the Salk Institute for Biological Studies, led a team that studied chemical modifications on more than 11,000 cells in the mouse cortex and how they influence brain circuitry.

• Arnold Kreigstein, a member of the University of California, San Francisco’s Kavli Institute for Fundamental Neuroscience. Kreigstein led a team that studied gene expression patterns in hundreds of thousands of developing brain cells. The researchers’ findings shed light on how the brain’s complex architecture comes to be, as well as the molecular signals that guide the development of specific cell types.

“Thanks to this groundbreaking collaboration, we now have a comprehensive understanding of the brain cells found in the motor cortex of the brain and their basic functional properties. The atlas will provide a springboard for future research into the structure and function of the brain within and across species,” said Francis Collins, Director of the U.S. National Institute of Health (NIH), in a statement about the atlas.

In addition to endowing the Kavl Neuroscience Institutes, The Kavli Foundation has also committed funding to the BRAIN Initiative, a public-private partnership that launched in 2013 to advance our understanding of the brain, and continues to support it in other ways.

This gene may drive intelligence

What makes the human brain unique? That question drives the research of Franck Polleux, a neuroscientist affiliated with Columbia University’s Kavli Institute for Brain Science. Building on a decade of work, Polleux and his team published a study in Nature in October that hones in on single gene that may enhance our ability. Polleux’s team expressed SRGAP2C — a human gene that appeared roughly 2.4 million years ago, around the time the Homo lineage began to evolve — in mice. When they looked for structural, functional and behavioral changes in the mice with the human gene, they found neurons in the cortex formed more connections and were more responsive to sensory input. The mice also learned a sensory-dependent task faster than mice without the human gene. The new study adds to the growing body of evidence that the duplication of genes like SRGAP2 over the course of evolution helped boost human intelligence and set us apart from other animals.

Finding the origin of seizures

For many patients with epilepsy, the only treatment option is surgery. However, there are few signposts to guide surgeons to the brain tissue in which seizures originate. As a result, seizures recur in anywhere from 30 to 70 percent of people who undergo epilepsy surgery. Johns Hopkins University graduate student Adam Li and principal investigator Sridevi Sarma set out to change that. They developed a computational model that predicts the likelihood that any single brain region contributes to a seizure, improving clinicians’ ability to diagnose and treat the disease. The model, recently described in an article in the journal Nature Neuroscience, relies on a new biomarker they call “neural fragility,” a measure of the instability of electrical connections in a brain region. The research team is now working toward commercializing discovery.

Read “Patterns in the Brain,” a recent Kavli profile of Sridevi Sarma, who is a member of the Kavli Neuroscience Discovery Institute at Johns Hopkins.

These immune cells protect neurons

Daniel Mucida, an immunologist at Rockefeller University who is is a member of the Kavli Neural Systems Institute, came to study the gut for immunology but “stayed for the neuroscience,” according to this interview. The enteric nervous system, a collection of 100-million neurons and glial cells, orchestrates the life-staining movement of nutrients, waste and fluid in our digestive tract. Past research by Mucida and his team showed that immune cells help protect enteric neurons from damage and even death following infection by pathogens like Samonella and parasitic worms. In a new study, published in October in the journal Cell, they describe how gut macrophages, which have been primed by prior infections, protect gut neurons from death when future infections happen. “We’re describing a sort of innate memory that persists after the primary infection is gone,” said Mucida in a news article. “This tolerance does not exist to kill future pathogens, but to deal with the damage that infection causes—preserving the number of neurons in the intestine.” The findings may eventually benefit people with intestinal disorders like Irritable Bowel Syndrome.

How the brain finds focus

The brain’s ability to cut through noise is important for all our senses, including touch. To perform a skilled hand movement like typing or dicing an onion, the brain needs to ignore tactile information coming in from all over the body that competes for our attention. In a new study in mice, published in the journal Science, neuroscientists James Connor and Eiman Azim describe the brain circuits that control how much sensory information flows from the hands to the rest of the brain. They show that inhibitory neurons in the cuneate nucleus, a part off the brainstem, enhance or suppress this flow, affecting the animal’s ability to carry out a skilled hand movement. The findings could help researchers design better prosthetics or even robots; they may also provide a blueprint for how the brain modulates other kinds of sensory feedback. Connor and Azim are based at the Salk Institute for Biological Studies, where Azim is a member of the Kavli Institute for Brain and Mind.