The human brain contains billions upon billions of neurons that interact with each other creating a vast network of synaptic connections. Because it is too complex, scientists around the world have been studying a simpler organism as a model to the human brain – a millimeter-long roundworm known as Caenorhabditis elegans (C. elegans).
C. elegans was the first multi-cellular organism to have its entire genome sequenced. They have only about 1,000 cells and they only need a few hundred neurons (302 in the hermaphrodite/female sex, 385 in the male) to move around, eat food and keep itself away from danger. In addition, C. elegans conveniently contain many of the same molecules found in the human nervous system.
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, said:
These connected networks serve as starting points for deciphering the neural control of C. elegans behavior. 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.
After many decades of research upon research, a team of scientists from Albert Einstein College of Medicine led by Dr. Emmons has managed to compile what they call the first complete map (wiring diagram) of its entire nervous system. Their achievement marks 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. The study has been published in the journal Nature.
Dr. Emmons said:
Structure is always central in biology. 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.
A connectome is a complete diagram of the neurons and their connections. It is, in a sense, a kind of neuronal map that could help researchers understand the role the nervous system plays in driving certain behaviors. This is of particular interest to a branch of scientific research dedicated to exploring the relationship between faulty connections and neurological disorders like schizophrenia, depression, and autism. There is a hypothesis among researchers that some neurological and psychiatric disorders, such as schizophrenia and autism, are “connectopathies” – problems caused by “faulty wiring.”
Dr. Emmons said:
This hypothesis is strengthened by the finding that several mental disorders are associated with mutations in genes that are thought to determine connectivity. Connectomics has the potential to help us understand the basis of some mental illnesses, possibly suggesting avenues for therapy.
In principle, if we can better understand how brain connectivity affects risk for mental illness, and if we can determine which specific neural circuits are the most relevant, we could develop new therapies that more precisely target the mechanisms that trigger illness onset.
Professor Alex Fornito, who was not involved in the study, from Australia’s Monash University leads a team at the Brain and Mental Health Lab leverage advanced imaging technologies who is mapping human brain connectivity to better understand its relationship to health and disease. He told New Atlas:
The brain is a heavily connected network of cells, and the way in which different cells connect to, and communicate with, each other gives rise to all of our thoughts, emotions, and behavior. It then follows that changes in brain wiring and communication should be closely related to one¹s risk for mental illness. These changes are likely to be subtle, as they often cannot be seen on a brain scan with the naked eye, and they are the product of a complex interplay between genes, environment, and development.
The Mind Of A Worm
The first map of the C. elegans nervous system was published back in 1986 by late British biologist Sydney Brenner, who in 2002 shared the Nobel Prize in Physiology or Medicine for his C. elegans research. Lab member John White led the efforts which involved analyzing neural structures visible on thousands of serial electron micrographs of the roundworm. These micrographs were images that consisted of a cross-sectional “slice” a thousand times thinner than a human hair. They had to 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.
Their phenomenal dedication that took 20 years is what launched the field of connectomics and established the roundworm as an essential animal model for the study of biology and human disease. Although, in the end, their map, titled “The Mind of a Worm” left out large portions of the worm’s body and included only the female (hermaphrodite) sex, not the male.
Filling In The Blanks
Dr. Emmons’ team took over to finish the job once and for all. They took Dr. Brenner’s old images and combined them with new roundworm electron micrographs using a specially developed software, forming complete wiring diagrams for both C. elegans sexes. These next level 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, even including estimates of the strength of those synapses.
Dr. Emmons explained to New Atlas:
It was simply digital imaging. A digital camera on the electron microscope, digital scanners for the old prints and the PC, which weren’t available to the original mappers in the 1970s. The new connectomes are now in digital format.
Upon analysis of the maps, they found some interesting new insights. They observed differences in the strength of some, particularly those related to reproductive functions in the female and those related to copulation in the male. “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.
Conclusion
Every time we advance our understanding of the brain’s connectivity with research like this, we come closer to new therapies for neurological disorders that don’t alter the brain as a whole like current drugs do, and instead zero in a specific cause.
Dr. Emmons said:
If known circuits that are dysfunctional can be identified, possibly therapies can be devised to enhance, or restore, or circumvent the functions of those circuits.
