“The brain is by far the most complex system in the known universe”, says Christof Koch, Chief Scientifi c Offi cer at the Allen Institute for Brain Science. “We need to have a complete listing of its parts and how they’re wired up, otherwise we’ll never fi gure it out.” And it’s that wiring map that Koch is setting out to fi nd. He has recently moved over from the California Institute of Technology in Pasadena to spearhead a new expansion at the Seattle-based Allen Institute, best known for creating gene-expression maps, or brain atlases, for mouse, monkey, and human brains, and making them freely available online. Now, the Institute’s industrial-sized laboratories—the engine rooms that enabled that huge undertaking—are again whirring into action, as the Institute aims to delve deeper into the inner workings of the brain, to fi nd out how it computes and processes information. If they achieve their 10-year mission, which is anchored around a recent US$300 million cash injection from benefactor and Microsoft co-founder Paul Allen, they stand to change the way we understand and therefore treat neurological disorders. The expansion will see the Institute’s workforce more than double to 350 people over the next 4 years. To steer this venture, they have recruited what Allan Jones, its CEO, describes as “all-stars in the fi eld of neuroscience”. Koch—a computational neuroscientist and long-time collaborator of Francis Crick, with whom he shared a fascination for the neural basis of consciousness—certainly fi ts that bill. As you would hope from a scientist of his standing, Koch is in no two minds about the scale, complexity, and importance of the task at hand. He off ers an analogy of how our current lack of foundational understanding about the building blocks of the brain stifl e the successful treatment of many neurological conditions. Fainthearted neurologists might want to look away. “Imagine if you take your car to a car mechanic, and the car mechanic says, ‘I don’t know how it works—I don’t even know how many parts there are—I just sort of mess around with it and after a while sometimes it works’”, he tells The Lancet Neurology. Drawing parallels with the pharmacological treatment of psychiatric and neurological disorders, he goes on to add: “it’s the same as a mechanic thinking ‘well there’s oil missing, we’ll dump some all over the car and hope maybe a little bit seeps into the motor where it’s actually needed’”. Wanting to “intervene in the circuits of the mind”, Koch—working on the assumption that the basic nuts and bolts of the brain are the same across all mammalian species—is focusing on the visual system in mice, aiming to understand, in vivo, every step along the information-processing pathway, from the eye all the way up to cortical computation. To do so he is building “observatories” that, using advanced electrophysiology or two-photon microscopy calcium imaging, allow him to “peer inside the brain of the mouse”. Also in his armoury is optogenetic manipulation. “With genetic engineering, you can essentially intro duce light switches into a specifi c subpart of any one cell, including brain cells”, he explains. “With beams of light you can turn those cells on or off selectively. You can do this with the precision of milliseconds. You can play the piano.” Rather than playing the piano, Koch will be playing (or at least using a simulator based on) Quake, a mazelike video game popular in the 1990s. Mice will be guided around this virtual reality maze, and along with Clay Reid, who has joined the team from Harvard Medical School, Koch will use optogenetic manipulation to switch on or off diff erent neuronal pathways, and “move from correlation to causation, from observing that a given circuit is activated whenever the animal makes a decision to inferring that this circuit is necessary for decision-making”, as he and Reid reported in a recent article. Koch is the fi rst to admit that although this research might improve treatments or preventive strategies for neurological disorders in the future, it is a long way from making a clinical impact. But there is another strand to the Institute’s expansion, headed up by Ricardo Dolmetsch, who joins from Stanford University, that should have neurologists’ ears pricking up. Dolmetsch will be working with inducible pluripotent stem cells, taking skin snips from individuals with neuropsychiatric and neuroFor the Allen Institute’s Brain Atlases see http://www.brainmap.org/
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May 1, 2013
Carina Braun 
Open Access