The wiring of brains is staggeringly complex. Our own brains have tens of billions of neurons connected through perhaps one hundred trillion synapses. This circuitry is the result of our development and experience; the neural activity that courses through and alters it, somehow accounts for our thoughts, our behavior, our memories. To echo Wheeler's synopsis of Einstein's theory of gravity: neural circuits tell activity how to propagate and neural activity tells circuits how to change. One hundred years from now, this brain circuitry will be known; today, for the first time, we can contemplate mapping it in detail. New forms of laser-scanning light microscopy and semi-automated electron microscopy allow high resolution imaging of “connectomes”—that is, complete neural wiring diagrams.
In 2004, Harvard established the Center for Brain Science (CBS) on its Cambridge campus, an interdisciplinary Center aimed at understanding neural circuits—their structure, their function, and how they are changed during development, aging, and disease. Jeff Lichtman and CBS launched the Connectome Project in 2005, to determine the detailed wiring diagrams of neural circuits. The Connectome Project has grown to include several other investigators, at Harvard (Sanes, Zhuang, Reid, and Pfister) and elsewhere. Support to launch the Connectome Project was provided by an anonymous gift and private matching gifts to Harvard and CBS. Subsequent support has come from the Gatsby Foundation, the Howard Hughes Medical Institute, an anonymous foundation, Microsoft Corporation, and the NIH.
Our efforts in the Connectome Project are focused on two imaging modalities, one using photons and the other using electrons. Light can be used to image living tissue and accommodates many spectral channels, but special tricks have to be used to resolve structures much smaller than the wavelength of light.
Here we use a direct approach: use electron microscopy to resolve the finest details in extremely thin slices of the brain circuit, reassemble the slices into a full three-dimensional image in a computer, and automatically trace out the circuit in all of its complexity by analyzing this “virtual brain.”