Team rewires a behavioral circuit in the worm using hydra parts

Date:
September 29, 2021
Source:
Marine Biological Laboratory
Summary:
New research highlights the development of HySyn, a system designed
to synthetically reconnect neural circuits using neuropeptides
from Hydra, a small, freshwater organism, into the model organism
C. elegans.



FULL STORY ==========================================================================
For two people to communicate in a loud, crowded room, they need to
be standing side by side. The same is often true for neurons in the
brain. But the same way a cell phone allows two people to communicate
clearly across the room, new research at the Marine Biological Laboratory
(MBL) opened up a new channel of communication in the worm C. elegans
brain.


==========================================================================
The research, published in Nature Communications, highlights the
development of HySyn, a system designed to synthetically reconnect
neural circuits using neuropeptides from Hydra, a small, freshwater
organism. (Neuropeptides modulate the activity of neurotransmitters to
increase or decrease the strength of impulses between neurons.) For the
first time, the researchers created genetic lines of mutant C. elegans
that expressed neuropeptides from the Hydra brain, creating an artificial synapse that rewired a behavioral circuit in the worm. Because none of
the other synapses in the brain, besides those fitted with the hydra
receptor and neuropeptide, could hear the "command," it was like giving
them a cell phone so they could communicate.

"These neuromodulatory peptides let you communicate at a distance," said
MBL Fellow Daniel Colo'n-Ramos of Yale University School of Medicine. "It
gives you more flexibility as a researcher to manipulate neurons that are
not adjacent to each other." Colo'n-Ramos, senior author on the paper,
was postdoctoral advisor for the paper's first author, former MBL Grass
Fellow Josh Hawk. The work and analysis was performed at the MBL and at
Yale University in Colo'n-Ramos's lab.

The researchers used a mutant line of C. elegans that was missing the
neural connection that controlled specific behavior -- the behavior that
told them that they were full and needed to stop searching for food. By
taking genes that encode a neuropeptide and its receptor from Hydra and
putting them into the C.

elegans worm, researchers were able to restore the neural circuit that
controls this behavior. They created two separate genetic lines -- one
that contained the neuropeptide and one that contained the receptor. The offspring of the pair contained the full neural peptide pathway. But,
according to Hawk, it's just one possible pathway to focus on.

"There are hundreds of neural peptides in Hydra, each of which could be
a different channel of communication," said Hawk. "To me, that's the
most exciting thing. This should open up a whole area that no one has
ever explored before." Hawk called this study a "proof of principle"
for the HySyn tool. Unlike most organisms, Hydra don't have a classic neurotransmitter system in the brain.

Instead, they rely completely on a net of neuropeptides. Each of
these Hydra neuropeptides has the opportunity for a unique line of communication. Hawk focused on a particular neuropeptide that creates
a slow-building signal, like the slow-building sensation of fullness
as you eat a meal. Connecting different neurons with this neuropeptide
could create a slowly rising pain response or strengthen a new memory.



========================================================================== There are many different types of communication in the brain. Some are
fast, on the order of milliseconds. But others are slower. That's what
Hawk was focusing on, the slow neuromodulatory response that told the
C. elegans: "I'm full, don't go seek out new food." The researchers
created an artificial, neuromodulatory synapse that told the C. elegans
it was time to relax.

"Usually, we can break things in science. That's very powerful. When we
break things we can see what they are necessary for, which also tells us
a little about how they work. But to really understand how they work,
you want to know if you can rebuild them -- fix them -- after they
are broken. And that is very hard to do," said Colo'n-Ramos. "That
[Hawk] could rebuild the connections between cells was very exciting
and innovative." Hawk wasn't just putting back missing components in
the C. elegans brain; he was putting in entirely new components from
Hydra -- fixing what was broken with a different set of parts. It showed
the researchers that it wasn't necessarily the identity of the parts themselves, but the communication and modulation between the synapses
that regulated the behavior.

Hawk said he hopes future research focuses on knocking out lines of communication in the brain and rebuilding them in a different way
with HySyn.

"This is the beginning of a set of tools, and as those tools are expanded,
it gives us a real ability to tweak connections in the brain in a variety
of permutations," he said.

"There's a lot of diversity of synaptic connection in any animal's
brain. Being able to pick and choose what to put in another organism
will help us untangle and understand how and why brains do what they do,"
said Hawk.



==========================================================================
The researchers are confident that HySyn will work in a variety of
organisms.

They tested it in vertebrate cells as well as in C. elegans.

Hawk added that he hopes researchers will focus on learning about the
strength of connections within the brain. "In theory, can you tear down
the worm brain and then rebuild it and find out what is lost when you
rebuild it certain ways.

It's what we did as kids: If you want to know how something works, you
break it down and rebuild it. But we need more tools to do that." HySin represents a contribution to that toolset.

In addition to his time as a Grass Fellow in 2019, Hawk was faculty member
for the MBL's Neural Systems and Behavior (NS&B) course from 2015-2019.

"Josh was able to leverage knowledge from the MBL and the people
he met and put all that knowledge together, with his own interests
in neuroscience, and make a significant contribution. This is what
programs like the Grass Fellowship and MBL help catalyze in science,"
said Colo'n-Ramos.

"It's like an emblematic MBL project," Colon-Ramos
said. "High risk, high reward. Lots of fun and
bringing in a lot of knowledge from the MBL community." ========================================================================== Story Source: Materials provided by Marine_Biological_Laboratory. Original written by Emily Greenhalgh. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Josh D. Hawk, Elias M. Wisdom, Titas Sengupta, Zane D. Kashlan,
Daniel A.

Colo'n-Ramos. A genetically encoded tool for reconstituting
synthetic modulatory neurotransmission and reconnect neural circuits
in vivo.

Nature Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-24690-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210929142810.htm

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