Scientific Understanding of Consciousness
Cerebral Cortex of Mouse — Allen Institute project
Nature 483, 97–398 (22 March 2012)
Neuroscience: Observatories of the mind
Nature | Comment
Christof Koch is at the Allen Institute for Brain Science, Seattle, Washington 98103, USA, and at the California Institute of Technology, Pasadena, California 91125, USA.
R. Clay Reid is at Harvard Medical School, Boston, Massachusetts 02115, USA, and will join the Allen Institute this summer.
Neuroscience now involves some 10,000 laboratories worldwide, pursuing distinct questions about the brain across a panoply of spatio-temporal scales and in a dizzying variety of animal species, behaviours and developmental time-points. At any large neuroscience meeting, attendees are struck by the pace of discovery, with 50,000 or more practitioners heading away from each other in all directions.
The Allen Institute for Brain Science in Seattle, Washington is initiating an experiment in the sociology of neuroscience — a huge endeavour that will involve several hundred scientists, engineers and technicians at the institute. Philanthropist Paul G. Allen, who founded the institute in 2003, has pledged US$300 million for the first four years of an ambitious ten-year plan that will accelerate progress in neuroscience, bringing his total commitment so far to $500 million. The goal is to attract the best young scientists and build a series of 'brain observatories', with the aim of identifying, recording and intervening in the mouse cerebral cortex, the outermost layer of the brain. Unlike the telescopes that peer at remote events in space and time, our instruments will track the flow of information in complex, interbraided neural circuits within a layer of tissue one millimetre thick.
The goal is to synthesize knowledge from all relevant disciplines — from genomics, anatomy and physiology to computer modelling — into a comprehensive theory of how the mouse uses its cortex to see. Following Allen's founding mandate for the institute, we will curate and publicly share all data and other resources (such as transgenic animals, probes and neuronal morphologies) for free, even before publication.
We believe that this initiative signals the arrival of large-scale science in a field that is populated by small groups. It will require rewarding the team, rather than a few lead investigators, for its collective effort. We envisage a time in the future when sophisticated, well-equipped brain observatories — 'mindscopes' — will complement the many academic neuroscience labs that will continue to make the bulk of discoveries.
Although the institute's project will focus on visual stimuli in mice, it will capture fundamental aspects of higher brain functions: perception, conscious awareness and decision-making, and how they lead to action. Once neuroscientists know the basic mechanisms in the mouse, they may start to understand more-complex forms of perception in other animals, including humans.
The project will start with the anatomy of cortical neurons, using molecular techniques to count and catalogue the diverse array of cells that transmit information into and out of the visual cortex, as well as those that lie solely within the cortex. Then we will observe and measure the electrical activity of a sizeable fraction of those neurons to learn how the function of the cortex follows from its structure. It is a big question, but less daunting if one considers the cortex as being composed of many copies of a basic local circuit.
Studies of the human brain have been revolutionized by magnetic resonance imaging, which reveals brain regions activated in real time. However, the underlying signals are slow and fuzzy, and brain regions are not the building blocks of the mind — neurons, in their immense complexity, are the atoms of perception and thought.
Fortunately, scientists can now study individual mammalian neurons in living brains, by making neurons fluoresce using genetic engineering. Neurons can be made to emit flashes of light when they are active or, using the most recent optogenetics techniques, can be controlled with light. In this way, researchers can transiently and reversibly control certain events in specific cell types at defined times. Perturbing the nervous system lets neuroscience 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.
Other technological advances enable neuroscientists to visualize every axon, dendrite and synapse in a circuit using three-dimensional electron microscopy. Another observatory in the visual-brain programme is designed to record the electrical activity of thousands of neurons simultaneously. When all of these techniques are stitched together, one can imagine a full physiological and structural characterization of entire brain regions.
Finally, we will use all of this information to generate realistic and dynamic computer models of the mouse cortex and its associated structures, and use these to build theories of how the visual cortex behaves. The modelling facility will be next door to the labs so that collaborators can mingle easily. This should shorten the time between prediction and experimental validation, a virtuous circle that will be iterated until the model faithfully reproduces the data.
There is a risk that this project will not work out as we anticipate, and that the various brain observatories — looking at anatomy, physiology and modelling, for example — will not synergize to form a sophisticated understanding of the mouse visual cortex. There is no guarantee that neuroscience is ready to become big science — but the only way to find out is to try.
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Science 23 March 2012: Vol. 335 no. 6075 pp. 1426-1427
A Vision of How Mouse Vision Can Reveal Consciousness' Secrets
Newsmaker Interview of Christof Koch by Yudhijit Bhattacharjee
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Neuroscientist Christof Koch has spent the past 25 years puzzling over the mystery of consciousness. A professor at the California Institute of Technology since 1986, Koch worked closely for years with the legendary Francis Crick exploring how the firing of neurons gives rise to perception, the experience of pleasure and pain, and other manifestations of conscious awareness.
Now, Koch is embarking on a seemingly narrower quest at the Allen Institute for Brain Science in Seattle, Washington, one that he nonetheless hopes will ultimately lead to breakthroughs in understanding consciousness. It's a 10-year project to study vision in the mouse brain, funded by a new donation of $300 million from Microsoft co-founder Paul Allen, who had already financed the start-up of the 9-year-old Seattle research center. The project, announced publicly this week, will build on the institute's foundational work of mapping the mouse brain to study how information flows through the mouse cortex—a millimeter-thick layer of tissue—to help the animal see. Although the specific goal is to understand vision, Koch says he and his colleagues also intend to study higher-order brain functions such as perception, decision-making, and conscious awareness.
And that, for Koch, is the bridge between the project and his grander desire to understand consciousness. “Once neuroscientists know the basic mechanisms of vision in the mouse, they may start to understand more complex forms of perceptions in other animals, including humans,”
Koch, who now spends three-quarters of his time at the Seattle institute as the project's chief scientific officer, has over the past several months described the project's vision to neuroscience labs around the country. The goal is to hire a few hundred neuroscientists, anatomists, geneticists—as well as technicians and engineers—to work toward the initiative's goal.
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