One of the most important goals of modern medical science is to understand in detail how the brain works. However, the brain is made up of billions of closely-mixed neurons, making it very difficult to visualize and map them.
If we fully understand the structure and tissues of the brain, it is expected that we can open a new chapter in brain science, such as discovering treatment routes for long-term intractable brain diseases.
A multidisciplinary research team of five research institutes led by the American Institute of Marine Biology (MBL) targets C. elegans. For the first time, the combined development path was uncovered and published in the journal’Nature’ on the 24th.
The research team computationally detected the hierarchical structure of the neurite tissue in the nematode neurofil. © Mark Moyle et al., Nature, 2021.
“The neural network is a tissue-level organization found in many different types of brains, from worms to humans,” said Daniel Colón-Ramos, a professor at Yale University, a senior author of the paper. Explained.
“However, a neural network is like spaghetti with numerous noodle strands intertwined, making it difficult to understand its structure and function.” Hundreds of neurons overlapping and touching each other, mixing through different parts of the brain, making thousands of choices.
Professor Colon-Ramos said, “In this paper, I’ve also added an explanation of neural network organization in a way that can be understood.”
Neurofil research of the nematode nematode
In this study, the research team focused on the neural ring neurophile, a bundle of 181 neurons that act as the central processing unit of the pretty little nematode.
And by innovatively combining network analysis and imaging strategies, they discovered that neural loops consist of four layers or strata. These layers contained separate areas for processing sensory information and moving behavior.
The research team mapped the sensory organs and muscle quadrants of the nematode to the relevant layers. Together, they discovered unique neurons that consolidate information across layers and create a kind of’cage’ around them.
Finally, using a high-resolution light sheet fluorescence microscope (diSPIM) developed by MBL fellow Dr. Hari Shroff and MBL researcher Abhisek Kumar of the National Institute of Biomedical Imaging and Biotechnology (NIBIB). It has been able to confirm how the layered structure appears in the developing pretty little nematode embryo.
Reconstructing the volume of the L4 nematode neuropil in serial sections of an electron microscope with neurons in the four highlighted layers (S1-red, S2-violet, S3-blue, and S4-green). Video capture. © Mark Moyle et al., Nature, 2021.
Postdoctoral researcher Mark Moyle of the Department of Neuroscience at Yale University, the first author of the thesis, said, “This research is the result of a paradigm shift that combines two fields of computational biology and developmental biology that are difficult to collaborate.” “I was able to understand, and based on this knowledge, I was able to identify the developmental processes leading to the correct combination of the structure.”
The authors believe that this approach could serve as a blueprint for understanding the brain neural networks in other animals.
From city buildings to boroughs
The pretty little nematode has a nervous system that can be best understood of all animals. More than 30 years ago, Dr. John White and Sydney Brenner’s team created the “connectome” of the nymph nematode, a wiring diagram of 302 neurons and about 7,000 synaptic connections between these neurons. Have been announced.
Since that pioneering study, almost all neurons in the nematode have been classified according to their characteristics, such as their shape, functional category, neural circuits to which they belong, and developmental cell lines.
But there was something missing. It is the overall picture of how these cells and neural circuits integrate spatially over time.
The dissected side of an adult hermaphrodite pretty little nematode. © WikiCommons/KDS444
Colon-Ramos’ team analyzed published data on all membrane contacts between 181 neurons in the neural ring. Then a new network analysis was applied to group cells into’neighborhoods’ based on their contact profiles. It was similar to the algorithm Facebook uses to recommend friends based on people’s common contacts.
This revealed the hierarchical structure of the neural network, and the research team was able to understand the cell-to-cell interaction in the context of the functional circuit and the functional circuit in the higher neural network structure ([동영상 1] Reference).
Professor Colon-Ramos said, “If you look at the structure, you realize that all the knowledge about the behavior of animals has its source in the brain structure.”
“Like this, rather than having a separate knowledge of New York’s East and West Sides, Brooklyn and Queens, looking at the whole structure will give you a better understanding of how the whole city fits and you will understand the relationships between neighboring regions.” I heard an analogy.
Therefore, it can now be described as “because these actions are direct circuits to the muscles, they are like reflexes” or “how this connects to other parts of the exercise program”. “If there is a structure, how is information processed?” “We can create new models of how they become and segmented into action.”
In order to highlight the neurophile, the final point of the nematode nematode growing over time was shown in a three-dimensional rotation. Neurofil has the shape of a bright ring structure at the top of the embryo. Video capture. © WikiCommons/KDS444
Reconstruct neural ring development and development
The brain is the product of development, starting with the division of an embryonic cell and ending with a complete organ.
Professor Colon-Ramos said, “Our next question is, how can we dictate the formation of a layered structure? How do all these crystals occur simultaneously in hundreds of cells and are produced in organized layers? How are these decisions coordinated through time and space? The points to do” he introduced.
“The hierarchical structure is the basic unit in which the brain is organized, and the retina is also a layer and the cortex is also a layer.” “You can create models that help you understand.”
This part of the study began in 2014, when Professor Colon-Ramos and Researcher Moil began working at MBL with microscope developers Dr. Schrov and Kumar.
“We started with the creation of a microscope (the diSPIM) that could see embryos with better spatial and temporal resolution than the tools of time,” Schrov said.
They then used a genealogical approach developed by Dr. Zhirong Bao, co-author of the paper at the Sloan Catering Institute, to identify all the cells of the nematode embryo. These results are classified on WormGUIDES.org. “It was a very painful process, but it was an important task to be done,” Dr. Schrov said.
A thesis published on the 24th of the scientific journal Nature. © Springer Nature / Nature
Achieve results through difficult collaboration
The research team has experienced a lot of frustration by adjusting the diSPIM system countless times and integrating other very important technologies while working together in the laboratory at MBL for many years. Was successful ([동영상 2] Reference).
Professor Colon-Ramos said, “This task would have been impossible if we could not shoot long-term using diSPIM and obtain smooth images.” “Many changes in technology development seemed to be gradual, but in reality it was possible to greatly increase the possibility. I was able to do something I couldn’t have done.”
“Often the changes we need are separated from the two areas where we use different vocabulary,” he said. “It took a long, intensive and thorough conversation to match this, which allowed us to collaborate at MBL.” .
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