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Nov 7, 2013

Cori Bargmann Has BRAINs on Her Mind

The neuroscientist and BRAIN Initiative co-chair gives GEN an update on the project that aims to “revolutionize our understanding of the human mind."

Cori Bargmann Has BRAINs on Her Mind

“For a lot of the way that different brain regions work together to generate complex functions, we’re really stumbling around in the dark,” says Dr. Bargmann. “The point of the BRAIN Initiative is to turn on some lights.”

  • Like the $100 million BRAIN Initiative which she co-chairs, Cori Bargmann’s interests span all levels, from the simplest neuronal structures to the most complex structure of all, the human brain. And interestingly, in the cases of both the BRAIN Initiative and Cori Bargmann, Ph.D., every level of complexity is important and every level contributes to the understanding of the whole.

    The “whole” in the case of the BRAIN Initiative (Brain Research Through Advancing Innovative Neurotechnologies) is complex indeed. Announced by President Obama on April 2, 2013, it aims to “revolutionize our understanding of the human mind and uncover new ways to treat, prevent, and cure brain disorders like Alzheimer’s, schizophrenia, autism, epilepsy, and traumatic brain injury.” To grasp the complexity of this goal, keep in mind that when studying a single human brain, researchers are dealing with a structure laced together with 10 billion neurons, 100,000 miles of biological wiring, and 100 trillion synapses.

    At 52 Dr. Bargmann, who co-chairs the project along with Stanford’s William Newsome, is well-qualified for the job, having spent her adult life as a star in the neuroscience field. She received her doctorate from MIT and now heads a laboratory at Rockefeller University. Her career has been littered with prizes including, most recently, sharing the million dollar Kavli Prize in Neuroscience in 2012 and, this year, the $3 million Breakthrough Prize for her studies on the relationships between genes, the nervous system, and behaviors in the roundworm C. elegans.

    C. elegans, one of the simpler animals to study, has only 302 neurons and 8,000 synapses, but its very simplicity makes it a powerful model for the analysis of neural circuits. Her work with C. elegans provided the first evidence for the detailed neuronal pathway between a specific olfactory receptor protein and behavior. Further, her lab has identified genes and neural pathways for C. elegans actions that determine how sensory inputs regulate these circuits. These fundamental principles of neural circuit logic also apply to mammals.

    The scope of C. elegans circuitry may be relatively simple, but when the President appointed Dr. Bargmann as co-chair of the BRAIN Initiative, the job included an extraordinarily broad and complex portfolio of objectives:

    • Help solve important economic and societal problems including brain diseases such as depression, Alzheimer’s, Parkinson’s, autism, PTSD, traumatic brain injuries, and schizophrenia;
    • Serve as a “North Star” for high-impact, multi-disciplinary collaborations among government, industry, universities, nonprofits, and philanthropists;
    • Create a foundation for industries and jobs of the future;
    • Capture public imagination and increase support for public policies that foster science, technology, and innovation; and
    • Inspire the next generation of scientists, engineers, and entrepreneurs

    But how to accomplish all this? “The announcement,” she said in a recent interview, “left some of us scratching our heads, trying to figure out how it would all fit together.”

  • Tackling BRAIN

    They had the precedent of the highly successful Human Genome Project (HGP)–which not incidentally generated $141 in economic activity for every dollar invested in it. However, as she puts it, “The HGP had a clearly defined end point. The BRAIN Initiative is both a much more amorphous and also a much more difficult problem.”

    She and 14 others scientists who serve on the committee concluded that the approach would have to be highly interdisciplinary. “We looked at each other and realized that, in spite of the many disciplines we all represented, we couldn’t speak for all the disciplines that would be needed.”

    Accordingly, this past summer they held workshops in San Francisco, New York, Boston, and Minnesota and invited top speakers to formulate ideas. The meetings were open so patient advocacy groups, physicians, and the lay public could also attend and provide comments. Among the disciplines represented: chemistry and molecular biology; electrophysiology and optics; structural neurobiology; computation, theory, and data analysis; and human neuroscience.

    They categorized the needed information. They would need to know how the parts of the brain were connected, the patterns of chemical and electrical activity that flow through the brain, and how perturbing the system affected activity and behavior. They also needed a scientific plan to study brain activity in time and space, given that the nervous system consists of interacting molecules, cells, and circuits across the entire body, and that important functions can occur in milliseconds, minutes, or take a lifetime.

  • New Technologies a Big Help

    Thinking about the timing for the BRAIN Initiative itself, she says, “It was propitious because of recent advances in technology, advances that are enabling neuroscience to leap beyond being an observational science into being a causal science as well.

    “Seven years ago,” she continues, “optogenetics began enabling us to enter the circuits of a brain with surgical precision, to increase or decrease their activity at will. Today’s optogenetic tools enable us to manipulate whatever neurons we desire, while the animal reports back to us by its behavior.”

    The second recently available technology increases the scope of activity that can be measured in the brain. “We used to be able to look at the brain’s 10 billion neurons either one neuron at a time, or with a satellite view of millions of neurons at a time, but neither view captures the circuits by which the brain actually works. Using improved multi-electrode recording arrays, as well as new optical recording methods with genetic and chemical sensors of neuronal activity, we can now simultaneously track the individual activity of hundreds of thousands of interconnected neurons.”

    To explain why this intermediate scale is important, she invites us to imagine trying to understand how a hospital works by following one random person around. “If we followed only the receptionist, we’d get a very distorted view of what happens there. A view of the hospital’s lights from an airplane won’t help us much either. We need to follow enough individual people to see the ways that doctors, patients, staff, and visitors interact with each other.

    “In the last few years,” she points out, “we’ve developed tools that can optically monitor tens of thousands of neurons. We are now able to monitor neuronal activity on the scale that we need to understand what circuits are actually doing.”

    A third development that makes this a propitious time for the BRAIN Initiative is the power of Big Data. It’s the ever-expanding computational and analytical power of Big Data that’s needed for dealing with the extraordinary volume of real-time data coming from current research.

    “The new technologies are not completely mature, and we’d like them to be ten times better, but as we link them together, we can better link together neural activity and behavior,” she summarizes.

    Although Dr. Bargmann has spent most or her research career studying the relatively simple organism C. elegans, she enjoys all levels of the scientific enterprise. “Science is a mystery with a solution, and being a scientist is a privilege. Over the course of my career I’ve watched surprising advances in human medicine emerge from the most basic scientific discoveries. It’s rewarding both because you can see what the field has accomplished in society and because you get the incredible joy of interacting with really smart people. I can’t imagine not being a neuroscientist. It’s just a great human experience.”



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