How to read the mind of a jellyfish

The human brain has 100 billion neurons, creating 100,000 billion connections. Understanding the precise circuits of brain cells that orchestrate all of our daily behaviors, such as moving our limbs, reacting to fear and other emotions, etc., is an incredibly complex puzzle for neuroscientists. But now fundamental questions in behavioral neuroscience can be answered with a much simpler new model organism: tiny jellyfish.

Caltech researchers have now developed a sort of genetic toolkit designed to tinker with Clytia hemisphaerica, a type of jellyfish about 1 centimeter in diameter when ripe. Using this toolkit, the tiny creatures have been genetically engineered so that their neurons individually glow with fluorescent light when activated. Because a jellyfish is transparent, researchers can then observe the glow of the animal’s neuronal activity as it behaves naturally. In other words, the team can read a jellyfish’s mind as it feeds, swims, evades predators, and more, to understand how the animal’s relatively simple brain coordinates its behaviors.

An article describing the new study appears in the journal Cell November 24. The research was conducted primarily in the lab of David J. Anderson, Seymour Benzer biology professor, Tianqiao and Chrissy Chen Institute for Neuroscience Leadership Chair, Howard Hughes Medical Institute Investigator and director of the Tianqiao and Chrissy Chen Institute for Neurosciences.

When it comes to model organisms used in laboratories, jellyfish are an extreme outlier. Worms, flies, fish and mice – some of the most commonly used laboratory model organisms – are all more closely related, genetically speaking, to each other than to a jellyfish. In fact, worms are evolutionarily closer to humans than to jellyfish.

“Jellyfish are an important point of comparison because they are so far removed from kinship,” says Brady Weissbourd, postdoctoral researcher and first author of the study. “They let us ask questions like: are there shared neuroscience principles in all nervous systems? Or, what might the early nervous systems have looked like? By exploring nature more broadly, we can also discover useful biological innovations. It’s important to note that many jellyfish are small and transparent, making them exciting platforms for systems neuroscience. This is because there are some amazing new tools for imaging and manipulating neural activity using light, and you can put a whole living jellyfish under a microscope and have access to the whole. of the nervous system at the same time.

Rather than being centralized in one part of the body like our own brain, the jellyfish brain is diffused throughout the animal’s body like a net. The different parts of a jellyfish’s body can function apparently autonomously, without centralized control; for example, a surgically removed jellyfish mouth may continue to “eat” even without the rest of the animal’s body.

This decentralized body plane appears to be a very successful evolutionary strategy, as jellyfish have persisted throughout the animal kingdom for hundreds of millions of years. But how does the decentralized nervous system of jellyfish coordinate and orchestrate behaviors?

After developing the genetic tools to work with Clytie, the researchers first looked at the neural circuits that underlie the animal’s eating behaviors. When Clytie hooks a brine shrimp in a tentacle, it folds its body to bring the tentacle to its mouth and simultaneously leans its mouth towards the tentacle. The team sought to answer: How does the brain of the jellyfish, apparently unstructured and radially symmetrical, coordinate this directional folding of the body of the jellyfish?

By examining the glowing chain reactions occurring in animal neurons as they ate, the team determined that a subnetwork of neurons that produces a particular neuropeptide (a molecule produced by neurons) is responsible for the folding. towards the interior of the body located in space. Additionally, although the jellyfish’s neural network initially appeared diffuse and unstructured, the researchers found a surprising degree of organization that only became visible with their fluorescent system.

“Our experiments revealed that the seemingly diffuse neural network that underlies the circular umbrella of the jellyfish is actually subdivided into plaques of active neurons, organized into quarters like slices of pizza,” says Anderson. “When a jellyfish catches a brine shrimp with a tentacle, the neurons of the ‘pizza slice’ closest to that tentacle activate first, causing that part of the umbrella to fold inward. , bringing the shrimp to the mouth. Importantly, this level of neural organization is completely invisible if you look at the anatomy of a jellyfish, even with a microscope. You have to be able to visualize the active neurons to see it, which we can do with our new system.

Weissbourd points out that this only scratches the surface of understanding the full repertoire of jellyfish behaviors. “In future work, we would like to use this jellyfish as a handy platform to understand precisely how behavior is generated by entire neural systems,” he says. “In the context of food passage, understanding how tentacles, umbrella and mouth coordinate with each other allows us to address more general issues of modularity function within nervous systems and how these modules fit together. coordinate with each other. The ultimate goal is not just to understand the nervous system of jellyfish, but to use it as a springboard to understand more complex systems in the future.

The new model system is easy to use for researchers anywhere. The jellyfish lines can be maintained in artificial seawater in a laboratory environment and shipped to collaborators who wish to answer questions using the small animals.

The article is titled “A Genetically Tractable Jellyfish Model for Evolutionary Systems and Neuroscience”. In addition to Weissbourd and Anderson, additional co-authors are Tsuyoshi Momose of Sorbonne University in France, graduate student Aditya Nair, former postdoctoral researcher Ann Kennedy (now Assistant Professor at Northwestern University) and former technician of Bridgett Hunt research. Funding was provided by the Caltech Center for Evolutionary Science, the Whitman Center of the Marine Biological Laboratory, the Life Sciences Research Foundation, and the Howard Hughes Medical Institute.

About Alma Ackerman

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