The brain is by far our most complex organ, with its billions upon billions of neurons that talk to each other through a vast network of synaptic connections. But there are simpler ways we can improve our understanding of it than mapping this impossibly intricate web. Enter a millimeter-long roundworm known as Caenorhabditis elegans, which scientists have been using as a model to study the human brain for some time, but have now compiled what they call the first complete map of its entire nervous system.
The reason the nervous system of C. elegans has served as a popular model for studying the human brain is largely due to its relative simplicity. Where the human brain contains around 100 billion neurons, C. elegans needs a grand total of 302 neurons to move around, eat food and keep itself away from danger. And conveniently, it contains many of the same molecules found in the human nervous system.
A complete diagram of these neurons and their connections is known as a connectome, and this kind of neuronal map could help us understand the role they play in driving certain behaviors in C. elegans. In turn, this could enlighten our understanding of the human nervous system, and what happens when these connections break down. This is of particular interest to a branch of scientific research dedicated to exploring the relationship between faulty connections and neurological disorders such as schizophrenia, depression and autism.
Leading the charge at Australia's Monash University is Professor Alex Fornito, whose team at the Brain and Mental Health Lab leverage advanced imaging technologies to map human brain connectivity and better understand its relationship to health and disease. He was not involved in the new study, but likens a complete human connectome to the Human Genome Project in terms of a scientific pursuit.
"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," Fornito tells New Atlas. "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."
Scientists actually published a map of the C. elegans nervous system back in 1986. The work involved analyzing neural structures on thousands of images and manually connecting the dots, creating a web of around 5,000 connections between the structures on one image and another. This work was critical in making the worm a popular model for studying human biology, but the map wasn't overly detailed, only describing the nervous system of the female worm and leaving out large sections of the body.
Fast-forward a few decades and scientists have now filled in the blanks. Led by Scott Emmons, a professor of genetics at Albert Einstein College of Medicine, the researchers combined these older roundworm images with new ones and then employed purpose-built software to stitch them together, forming complete wiring diagrams for both sexes of C. elegans. These include all the connections between the neurons and the worm's muscles, tissues like the gut and skin, and the synapses between the muscle cells.
"It was simply digital imaging," Emmons explains to New Atlas. "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."
The early surveys of these maps reveal some interesting insights. For example, Emmons says the synaptic pathways between the two sexes are similar, but 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.
The researchers describe this achievement as a major milestone in the field of connectomics, as it is known, and say the complete diagram can serve as a starting point for further exploration of how these neural connections control the worm's behavior. And because of the molecules it shares with the human nervous system, it could help us better understand that and possibly even uncover new therapeutic treatments for some neurological conditions further down the track.
"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," Emmons tells us.
This is obviously a long way off. Emmons says that a complete human connectome is a realistic goal but is many years, and possibly decades, away. But every time we advance our understanding of the brain's connectivity, we edge 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.
"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," says Fornito.
You can hear from Emmons, the lead author on the new study, in the video below, while the research was published in the journal Nature.
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