Scientists rewired the brain of a mutant worm using parts of a hydra

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Brains aren’t the easiest organs to study, with their delicate wiring and the subtle whispering of messages from neurotransmitters. Now that research might be a little easier, as we’ve learned that we can swap some critical chemical systems with the host animal by not being smarter.

In a proof-of-concept study conducted by a team of American researchers, the microscopic worm Caenorhabditis elegans was genetically gifted pieces of a nervous system taken from a radically different creature – a curious freshwater organism known as the Hydra.

The exchange was reminiscent of teaching a foreign language to a specific brain circuit, and finding that it does its job as well as before.

“There is a great diversity of synaptic connections in the brain of any animal”, Explain Josh Hawk, neuroscientist at the Marine Biological Laboratory in Massachusetts.

“Being able to choose what to put in another organism will help us unravel and understand how and why brains do what they do.”

Like us, the nematode C. elegans has a closely related nervous system governed by chemical messengers called neurotransmitters. Different circuits use their own types of neurotransmitters, which are released in the thin spaces between neurons called synapses.

For the most part, these narrow voids are where a brain does a lot of its work. Synapses are the logic gates computer circuits in the brain – blocking some signals, enhancing others, turning chemical fluctuations into something deep.

Neuroscientists can understand a lot about the functions of a nervous system by tinkering with this traffic light system using a variety of drugs, genetic modifications, and light-actuated switches.

Turning things on and off and watching chaos can tell you a lot about how a nervous system works. After all, much of what we’ve learned in neuroscience has emerged from observing the consequences of a broken brain.

“But to really understand how they work, you want to know if you can rebuild them – fix them – once they’re broken. And that’s very difficult to do,” said lead author of the study, Daniel Colón-Ramos of Yale University School of Medicine.

The trick in this case was to “fix” a broken circuit in the nematodes with parts borrowed from another organism, which runs on very different biochemical software. Hydra are not worms. They are most closely related to the sea anemone, with tiny, sprawling bodies ruled by a spread of loosely connected neurons arranged in a simple net-like structure.

Stranger still, the cells making up this neural mesh communicate with each other by projecting peptides which then diffuse into the hydra’s body, activating the corresponding receptors on other cells.

“There are hundreds of neuronal peptides in Hydra, each of which could be a different communication channel “, said Falcon.

“For me, this is the most exciting thing. It should open up a whole area that no one has ever explored before.”

To test the concept, Hawk and his colleagues genetically modified specimens of C. elegans to lose their ability to feel full. These hungry worms showed foraging behaviors regardless of how much food they had consumed, giving researchers clear activity to watch out for in their mutants.

From this group of worms, they created two new lineages – one with the gene for a hydra neuropeptide and another with the corresponding receptor gene.

The offspring between the two families united the two halves into one nervous system. Without their usual ‘I’m full’ brain circuitry, they had to rely on the hydra’s neuropeptides to signal the end of mealtime.

Successful exchange is only the first step. Thanks to the functioning of hydrous neuropeptides, it is possible to separate the neurons that use them to signal and make them communicate at long distance.

“It gives you more flexibility as a researcher to manipulate neurons that are not adjacent to each other”, said Colon-Ramos.

This specific combination of messenger and receptor, dubbed HySyn, may just be the start of a vast toolkit of replacement transmitters that researchers could use to decipher the intricacies of neural circuitry.

This research was published in Nature Communication.


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