By David Orenstein, The Picower Institute for Knowing and Memory
October 17, 2023
MIT researchers studied a single nerve cell in the C. elegans worm, finding its role in controling numerous habits. This nerve cell utilizes different neurotransmitters and can “borrow” serotonin, potentially providing insights into psychiatric treatments in more complex organisms.
Study discovers that in worms, the HSN neuron uses several chemicals and connections to orchestrate egg-laying and locomotion over the course of several minutes.
A new MIT research study that focuses on a single cell in one of natures most basic worried systems supplies an in-depth illustration of how individual nerve cells can utilize numerous ways to drive complex habits.
In the C. elegans worm, which just has 302 afferent neuron, the nerve cell HSN releases several chemicals and makes numerous connections along its length to not just control the animals instantaneous egg laying and locomotion, however likewise to then slow the worm down for numerous minutes after the eggs are laid. To control that latter phase of the habits, HSN transfers the neurotransmitter serotonin to a fellow neuron, which re-releases it to influence behavior minutes later on.
” Our results expose how a single neuron can influence a broad suite of behaviors over multiple timescales and show that neurons can borrow serotonin from one another to control behavior,” the scientists report in Current Biology.
The studys senior author is Steven Flavell, associate teacher in The Picower Institute for Learning and Memory and the Department of Brain and Cognitive Sciences. Postdoc Yung-Chi Huang is the studys first author.
In a C. elegans worm, the neuron HSN has a vital role in directing numerous collaborated behaviors. This image identifies HSN in green, revealing its extension all the method to the worms head (identified in red). Credit: Flavell Lab/Picower Institute
A Busy Neuron
Heading into the research study, HSNs connections to other neurons had actually currently been mapped (C. elegans is the only animal where the complete connectome among nerve cells is understood), and it had likewise been associated with egg-laying. Flavells lab, on the other hand, has observed that when the worms lay eggs, they speed throughout patches of food a bit like a farmer will drive a tractor to distribute seeds throughout fertile soil. Additionally, researchers had observed that when HSN is ablated, worms do not engage in a particular feeding behavior of slowing down to dine on patches of food.
However how this single nerve cell had these relatively paradoxical effects on habits (egg laying, speeding up to do that, and slowing down after) remained a mystery. Flavell and Huangs team utilized a wide array of strategies and experiments to discover how HSN does its numerous jobs.
To develop that HSN undoubtedly has a causal role in controlling these behaviors, they manipulated the neurons activity utilizing optogenetics, a method in which cells are genetically crafted to be controlled by flashes of light. In addition to validating HSNs key role in egg laying, these and other hereditary manipulation experiments likewise validated that HSN causes the worm to accelerate and then, after a bout of roaming and egg laying, to decrease for numerous minutes. The lab also tracked the electrical activity of HSN during these habits (by tracking the flow of calcium ions within the cell as animals freely moved) and saw that specific patterns of the cells activity were connected with egg laying and mobility.
Lots Of Molecular Means
Having actually established that HSN causes the three related behaviors, the laboratory then zeroed in on how it does so.
HSN is understood to launch a large range of neurotransmitter chemicals consisting of serotonin, acetylcholine, and various peptides. To figure out how the neuron drives rapid mobility, the group methodically knocked out each HSN neurotransmitter and then stimulated HSN to see whether the worms might still speed up when HSN could not produce one chemical or the other.
Knocking out serotonin in HSN, on the other hand, handicapped the worms slowing behavior. When HSN couldnt produce serotonin, for instance, NSM could not slow the worms down. The group even more showed that NSM uses the serotonin transporter SERT (called MOD-5 in C. elegans) to take up HSNs serotonin and re-release it.
Physiological Analysis
Turning to HSNs anatomy, the group recognized that control of mobility and control of egg-laying took place along various points of HSNs axon. Cutting HSNs axon in between the midbody and head did not interfere with the animals egg-laying, but did avoid the coordination of egg-laying and locomotion, suggesting that HSNs projection to the head collaborates HSNs action on the egg-laying circuit with its action on the mobility circuit.
In all, the research study demonstrated how HSN utilizes lots of parallel neurotransmitter outputs in various ways to control the animals behavior.
” Our results show how cellular morphology, numerous transmitter systems, and non-canonical modes of transmission like neurotransmitter “loaning” enhance a single nerve cell with the capability to orchestrate several features of a behavioral program,” the authors wrote.
The finding that nerve cells can take up and re-release serotonin produced by other neurons to control habits reveals an unique function of serotonin signaling that could have crucial medical implications, Flavell states. The particle that uses up the serotonin, SERT/MOD -5, is the target of serotonin-specific reuptake inhibitors (SSRIs) like Prozac. This research study raises the possibility that SSRIs might affect how neurons share serotonin with one another, which might be appropriate for their mode of action in treating a wide range of psychiatric disorders.
Referral: “A single nerve cell in C. elegans orchestrates multiple motor outputs through parallel modes of transmission” by Yung-Chi Huang, Jinyue Luo, Wenjia Huang, Casey M. Baker, Matthew A. Gomes, Bohan Meng, Alexandra B. Byrne and Steven W. Flavell, 27 September 2023, Current Biology.DOI: 10.1016/ j.cub.2023.08.088.
In addition to Huang and Flavell, the papers other authors are Jinyue Luo, Wenjia Huang, Casey Baker, Matthew Gomes, Bohan Meng, and Alexandra Byrne.
The National Institutes of Health, the National Science Foundation, the McKnight Foundation, The Alfred P. Sloan Foundation, The Picower Institute, and The JPB Foundation contributed funding for the study.
Heading into the study, HSNs connections to other nerve cells had currently been mapped (C. elegans is the only animal where the full connectome amongst neurons is understood), and it had actually also been associated with egg-laying. In addition to validating HSNs essential role in egg laying, these and other hereditary adjustment experiments also validated that HSN causes the worm to speed up and then, after a bout of roaming and egg laying, to slow down for numerous minutes. To identify how the nerve cell drives rapid mobility, the team systematically knocked out each HSN neurotransmitter and then stimulated HSN to see whether the worms could still speed up when HSN couldnt produce one chemical or the other. Turning to HSNs anatomy, the group discerned that control of mobility and control of egg-laying occurred along various points of HSNs axon. Cutting HSNs axon between the midbody and head did not disrupt the animals egg-laying, however did prevent the coordination of egg-laying and mobility, suggesting that HSNs forecast to the head collaborates HSNs action on the egg-laying circuit with its action on the locomotion circuit.
