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First Complete Wiring Diagram of a Nervous System

In a study published online this past July in Nature, Einstein researchers described the first complete wiring diagram of the nervous system of an animal, the roundworm Caenorhabditis elegans, used by scientists worldwide as a model organism. The study included adults of both sexes and revealed substantial differences between them.

The findings mark a major milestone in the field of “connectomics”—the effort to map the myriad neural connections in a brain, brain region, or nervous system to find the specific nerve connections responsible for particular behaviors.

“Structure is always central in biology,” says study leader Scott Emmons, Ph.D., professor of genetics and in the Dominick P. Purpura Department of Neuroscience and the Siegfried Ullmann Chair in Molecular Genetics at Einstein.

Copyright 2019, Springer Nature

“The structure of DNA revealed how genes work, and the structure of proteins revealed how enzymes function. Now the structure of the nervous system is revealing how animals behave and how neural connections go wrong to cause disease,” Dr. Emmons says.

Researchers have hypothesized that some neurological and psychiatric disorders, such as schizophrenia and autism, are “connectopathies”—that is, problems caused by “faulty wiring.” “This hypothesis is strengthened by the finding that several mental disorders are associated with mutations in genes that are thought to determine connectivity,” Dr. Emmons says. “Connectomics has the potential to help us understand the basis of some mental illnesses, possibly suggesting avenues for therapy.”

Because C. elegans is so tiny—adults are just one millimeter long and have only about 1,000 cells—its simple nervous system of a few hundred neurons (302 in the hermaphrodite/female sex, 385 in the male) makes it one of the best animal models for understanding the billions-times-more-complex human brain. It was also the first multi-cellular organism to have its entire genome sequenced.

Dr. Emmons’ study builds on the groundbreaking work of the late South African-born biologist Sydney Brenner, who in 2002 shared the Nobel Prize in Physiology or Medicine for his C. elegans research. Dr. Brenner’s laboratory published the first map of the C. elegans nervous system in 1986, after painstakingly analyzing neural structures visible on thousands of serial electron micrographs.

That tour de force effort, 20 years in the making, launched the field of connectomics and established the roundworm as an essential animal model for studying biology and human disease.

“Since the roundworm nervous system contains many of the same molecules as the human nervous system, what we learn about the former can help us understand the latter,” says Dr. Emmons, who is currently studying how the roundworm connectome is encoded by its genome.

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