WORM ATLAS: An in-progress 3D reconstruction of the C. elegans connectome. Dots represent the cell bodies of neurons; long lines represent the neurons' axons and dendrites. Image: The OpenWorm Project, image generated by neuroConstruct
In the 1970s biologist Sydney Brenner and his colleagues began preserving tiny hermaphroditic roundworms known as Caenorhabditis elegans in agar and osmium fixative, slicing up their bodies like pepperoni and photographing their cells through a powerful electron microscope. The goal was to create a wiring diagram—a map of all 302 neurons in the C. elegans nervous system as well as all the 7,000 connections, or synapses, between those neurons. In 1986 the scientists published a near complete draft of the diagram. More than 20 years later, Dmitri Chklovskii of Janelia Farm Research Campus and his collaborators published an even more comprehensive version. Today, scientists call such diagrams "connectomes."
So far, C. elegans is the only organism that boasts a complete connectome. Researchers are also working on connectomes for the fruit fly nervous system and the mouse brain. In recent years some neuroscientists have proposed creating a connectome for the entire human brain—or at least big chunks of it. Perhaps the most famous proponent of connectomics is Sebastian Seung of the Massachusetts Institute of Technology, whose impressive credentials, TED talk, popular book, charisma and distinctive fashion sense (he is known to wear gold sneakers) have made him a veritable neuroscience rock star.
Other neuroscientists think that connectomics at such a large scale—the human brain contains around 86 billion neurons and 100 trillion synapses—is not the best use of limited resources. It would take far too long to produce such a massive map, they argue, and, even if we had one, we would not really know how to interpret it. To bolster their argument, some critics point out that the C. elegans connectome has not provided many insights into the worm's behavior. In a debate* with Seung at Columbia University earlier this year, Anthony Movshon of New York University said, "I think it's fair to say…that our understanding of the worm has not been materially enhanced by having that connectome available to us. We don't have a comprehensive model of how the worm's nervous system actually produces the behaviors. What we have is a sort of a bed on which we can build experiments—and many people have built many elegant experiments on that bed. But that connectome by itself has not explained anything."
Because a lone connectome is a snapshot of pathways through which information might flow in an incredibly dynamic organ, it cannot reveal how neurons behave in real time, nor does it account for the many mysterious ways that neurons regulate one another's behavior. Without such maps, however, scientists cannot thoroughly understand how the brain processes information at the level of the circuit. In combination with other tools, the C. elegans connectome has in fact taught scientists a lot about the worm's behavior; partial connectomes that researchers have established in the crustacean nervous system have been similarly helpful. Scientists are also learning how to make connectomes faster than before and to enhance the information they provide. Many researchers in the field summarize their philosophy like this: "A connectome is necessary, but not sufficient."
"Some people say we don't know anything about how C. elegans's brain works and I am like, 'Yes, we do!'" says Cornelia Bargmann of The Rockefeller University, who has studied the nematode for more than two decades and attended the Columbia debate. "A lot of what we know about C elegans's rapid behaviors we have learned through and with the connectome. Every time we do an experiment, we look at those wiring diagrams and use them as a starting point for generating hypotheses."