In a study published in Nature, researchers describe 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 includes adults of both sexes and reveals 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," said study leader. "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."

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," said the senior author. "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.

For the new study, the team analyzed new roundworm electron micrographs as well as Dr. Brenner's old ones and pieced them together using specially developed software to create complete wiring diagrams of entire adult animals of both C. elegans sexes. The diagrams include all connections between individual neurons, connections from neurons to the worm's muscles and other tissues, such as the gut and skin, and synapses between the muscle cells, with estimates of the strength of those synapses.

"While the synaptic pathways in the two sexes are substantially similar, a number of the synapses differ in strength, providing a basis for understanding sex-specific behaviors," said the senior author. The primary sex differences pertain to reproductive functions: in vulval and uterine muscles and the motor neurons that control them in the hermaphrodite; and in the large number of additional neurons, sex muscles, and connections in the tail that generate the circuits for copulation in the male. But beyond these, a surprising number of synapses between neurons in central pathways shared by both sexes also appear to differ considerably in strength.

"These connected networks serve as starting points for deciphering the neural control of C. elegans behavior," said the senior author. "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."

https://www.einstein.yu.edu/news/1356/first-complete-wiring-diagram-of-an-animals-nervous-system/

https://www.nature.com/articles/s41586-019-1352-7