First complete wiring diagram of an animal's nervous system

Caenorhabditis elegans.

In a study published online today in Nature, researchers at Albert Einstein College of Medicine 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 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. "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 Dr. Emmons. "Connectomics has the potential to help us understand the basis of some mental illnesses, possibly suggesting avenues for therapy."

A Model Organism

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 British biologist Sydney Brenner, who in 2002 shared the Nobel Prize in Physiology or Medicine for his C. elegans research. Dr. Brenner's laboratory, in an effort led by laboratory member John White, published the first map of the C. elegans nervous system in 1986, after painstakingly analyzing neural structures visible on thousands of serial electron micrographs of the roundworm. Each image consisted of a cross-sectional "slice" a thousand times thinner than a human hair. He and his colleagues manually "connected the dots" between each slice, linking the structures from one image to another to create detailed representations of the nerves and the 5,000 or so connections (synapses) among them.

The tour de force effort by Drs. Brenner and White, 20 years in the making, launched the field of connectomics and established the roundworm as an essential animal model for the study of biology and human disease. But their map, informally called "The Mind of a Worm," skipped large portions of the worm's body and included just one of the sexes—the hermaphrodite, or female—not the male.

Taking Up the Baton

For the new study, Dr. Emmons' 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 Dr. Emmons. 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 Dr. Emmons. "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."

Dr. Emmons is currently studying how the roundworm connectome is encoded by its genome.

More information: Whole-animal connectomes of both Caenorhabditis elegans sexes, Nature (2019). DOI: 10.1038/s41586-019-1352-7 , https://nature.com/articles/s41586-019-1352-7

Journal information: Nature

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By Albert Einstein College of Medicine

Early Plans

As early as 1945, Yeshiva University President Dr. Samuel Belkin envisioned the creation of a new medical school. Encouraged by influential public figures, he persuaded the Board of Trustees to initiate discussions with the New York State Board of Regents to amend the University’s charter to include the granting of the degree of Doctor of Medicine, discussions that were successfully completed on December 15, 1950. In June, 1951, Dr. Belkin and New York City Mayor Vincent Impellitteri entered into an agreement whereby the professional care of all patients in the 1,400-bed Bronx Municipal Hospital Center then under construction would be the responsibility of the faculty of the College of Medicine. On March 15, 1953, the day following his 74th birthday, Professor Albert Einstein formally agreed to permit his name to be used for the first medical school to be built in New York City since 1897.

Ground was broken for the first building, now known as the Leo Forchheimer Medical Sciences Building, in October, 1953. Its partial completion was effected in time to welcome the first class of 53 men and three women medical students and about 75 faculty members on September 12, 1955. Entering class size was progressively increased to its present number of 180 students. The total student body now numbers well over 800, including postgraduates attending the Sue Golding Graduate Division of Medical Sciences and the Belfer Institute for Advanced Biomedical Studies.

Early Growth

To accommodate the expanding research programs of the College of Medicine, the Ullmann Research Center for Health Sciences was completed in 1964. More efficient and effective coordination of studies into intellectual disabilities was greatly facilitated by the construction in 1970 of the Rose F. Kennedy Center for Research in Mental Retardation and Human Development on the campus of the Bronx Municipal Hospital Center. The Arthur B. and Diane Belfer Educational Center for Health Sciences, which opened in 1972, provided additional laboratories and classrooms for basic science instruction as well as the 260-seat Riklis Auditorium. The Irwin B. and Sylvia Chanin Institute for Cancer Research, devoted exclusively to basic investigations into malignant processes, opened in 1978. Further enlarging the research capabilities of the College of Medicine, the Samuel H. and Rachel Golding Building, a 10-story biomedical research facility, opened in 1996.

Recent Expansion

In 2008, the College of Medicine embarked on a major expansion program that effectively doubled the size of its campus. Central to that expansion, and a critical part of Einstein’s campus master plan, was the opening of the Michael F. Price Center for Genetic and Translational Medicine/Harold and Muriel Block Research Pavilion, a 223,000 square-foot biomedical research building that houses 40 laboratories. These state-of-the-art facilities bring together world-class scientists and the most advanced technology to facilitate the translation of discoveries at the molecular level to the treatment, cure and prevention of disease.

In 2009, the College of Medicine leased Van Etten from Jacobi/Bronx Municipal Medical Center for 99 years. Einstein soon began transforming the 350,000-square-foot former tuberculosis sanatorium. It now houses the Ruth L. Gottesman Clinical Skills Center, dozens of wet and dry labs, and several of Einstein’s aging research programs, including the Einstein Aging Study, the Longevity Genes Project and Central Control of Mobility in Aging study.

In 2013, the D. Samuel Gottesman Library, located in the Forchheimer Building, underwent a transformation. The lower stacks were turned into a modern, large-group learning studio, and the upper stacks were converted into intimate, small-group learning studios conducive to collaborative, project-based activities. Both areas are designed to foster a dynamic educational experience rooted in team-based learning.

Renovations have taken place in numerous buildings around campus, including the newly renamed Harold and Muriel Block Building, the Irwin S. and Sylvia Chanin Institute for Cancer Research, the Ullmann Research Center for Health Sciences, and the Kennedy Building.

Going Forward

In September 2015, Einstein became a part of Montefiore. As we enter what will surely be a golden age of medicine, the College of Medicine remains steadfast in its core missions: educating students to become caring, curing physicians and world-class scientists, and fostering pioneering programs in biomedical and translational research that will lead to superb patient care. We continue to be guided by the high academic and humanistic values exemplified by our namesake and by the shared Einstein-Montefiore mission of the pursuit of social justice in meeting the healthcare needs of all individuals.

Albert Einstein College of Medicine

(Source: phys.org; July 3, 2019; https://tinyurl.com/yysenmna)
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