The strength of inductive science, however, is that new observational tools often reveal unexpected things that force you to confront the disconnect between the current worldview and the revealed world—especially when you have young colleagues, who bring fewer biases to biological phenomena. Microscopes are particularly valuable tools for this endeavor in neurobiology because they are a direct link between cell-biological phenomena and the visual system, our most sophisticated sensory mechanism.

In the 1990s, neuroscience turned sharply toward molecular genetics. Many remarkable technological advances have resulted, including the ability to make mice that express fluorescent proteins from jellyfish. In our lab and others', these animals have dramatically improved the ability to visualize neurons over time in living animals (so-called intravital microscopy). Automated microscopes and computational tools also allow assessment of the structure of many individual nerve cells in one preparation. Together, these innovations may enable us to describe all the synaptic linkages in neuronal circuits, what I like to call "connectomics." By providing a complete description of the wiring of the brain, these maps may give us a window into the inner workings of the mind and may even yield insights into "connectopathies," where the wiring has gone awry.

Some optimists believed that knowing the complete genome sequences of animals meant it was just a matter of time before we would understand essentially all biological phenomena as molecular cascades. My sense is that this optimistic view now holds less sway. So many concurrent and interacting molecular reactions occur within cells that scientists simply cannot reduce a living cell, much less a multicellular organism, to just so many bags of molecules, hoping to extrapolate the organism's full repertoire of behaviors. Observational approaches of neuronal behavior may provide a much-needed bridge between molecules and brains. Just as nature videographers working in the wild show us a far better view of behavior than we could obtain by observing specimens in a museum case or even a zoo, intravital imaging helps us move out of the culture dish and into the real jungle of the brain.

Interview by Julie Corliss

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