Behavior: C. elegans does a spit take

Eating can turn into spitting because individual parts of a muscle cell are able to contract in different ways.
  1. Michael Hendricks  Is a corresponding author
  1. Department of Biology, McGill University, Canada

Like all animals, the tiny worm Caenorhabditis elegans dislikes bad-tasting food – a probably common occurrence in the compost where it lives (Frézal and Félix, 2015). In fact, recent data showed that just like you and I, the worms can spit out foul-tasting chemicals such as reactive oxygen species (Bhatla and Horvitz, 2015b; Bhatla et al., 2015a). To explain how these types of behaviors can emerge, scientists often focus on correlations between brain activity, sensory inputs and behavioral outputs. However, while neural activity understandably comes to the fore, attempts at mechanistic explanations will always fall short if they do not include another class of excitable cells that are essential for behavior: muscles. Now, in eLife, Robert Horvitz and colleagues from Massachusetts Institute of Technology (MIT) and University of California, Berkeley – including Steven Sando as first author – report on the impressive complexity in muscle coordination required for worms to spit out their food (Sando et al., 2021).

The feeding organ of C. elegans contains a pump that ingests and grinds bacteria before passing them on to the gut. Like the nervous system in the guts of mammals, this ‘pharynx’ is somewhat a fiefdom of its own. Formed of 20 neurons and 20 muscle cells isolated from the rest of the nervous system (both physically and in terms of neuronal connections), the organ regulates food intake autonomously (Avery and Shtonda, 2003; White et al., 1986). In particular, two structures in the pharynx ensure that the worms can eat properly: the metastomal filter stops large particles from entering while the pharyngeal valve acts as a one-way check and keeps food moving in the right direction (Fang-Yen et al., 2009). So how can such a dedicated pump suddenly reverse direction?

By analyzing high-speed videos, Sando et al. noticed that when the worms are spitting, the rate of pumping increases in the pharynx. This seems counterintuitive: if food tasted unpleasant, you probably would not start gorging on it even faster. However, the metastomal filter and pharyngeal valve are held open during this increase, allowing the contents of the pharynx to be rapidly flushed back into the environment.

To examine how the valve stayed open during spitting, the team then focused on a set of muscles known as pm3s. These three muscle cells contract and relax rhythmically to help the pharynx pump food, and to allow the pharyngeal valve to open and close. However, during spitting, pm3s play two simultaneous roles: the anterior portions of the cells stay contracted to keep the valve open, while their posterior sections rapidly contract and relax to drive food out of the pharynx.

To confirm that these changes came from pm3s themselves – and not from forces impinging on the muscle or the valve – Sando et al. had a closer look at muscle activation during pumping and spitting. To do so, they expressed a calcium-sensitive fluorescent protein in pharyngeal muscles, as the concentration of calcium ions increases inside a contracting cell. This revealed that in spitting animals, sustained calcium signals were localized around the pharyngeal valve. This result is consistent with the anterior portion of pm3s (and only this portion) contracting to hold the valve open. But how is this complex activity state of pm3 regulated?

A pharyngeal neuron call M1 is essential for spitting – killing this cell with a laser stops the spitting response in worms. Based on the cells that M1 connects to and further experiments, Sando et al. suggest that this neuron integrates multiple signals that correspond to noxious tastes. The signaling output of the M1 neuron varies in strength according to these inputs: weak activation leads to opening of the pharyngeal valve, and only strong activation results in the valve opening and increased pumping necessary to eject food. In turn, various degrees of spitting behavior could emerge from these different inputs thanks to local contraction of cellular portions of the pm3 muscles.

Sando et al. stopped short of exploring the cellular mechanisms that allow local contraction of pm3s. In other systems, like mammalian smooth muscle, contractility patterns are determined by the spatial and temporal dynamics of calcium ions. These patterns arise from a complex interplay between various sources of ions and the channels or regulatory proteins that compartmentalize and shape calcium dynamics inside a cell. A similar mechanism could be happening here, with various levels of M1 activation targeting different sources of – or regulatory pathways for – intracellular calcium ions in pm3s.

Taken together, the results from Sando et al. highlight that muscles are not just passive conduits for neural commands: instead, they can exhibit dynamics that arise from the interplay between neural signals and their own, varying physiological properties. The functional insights of this study, along with the power of C. elegans genetics, offers an opportunity to study complex muscle dynamics and their neural regulation in a compact and accessible system.

References

    1. White JG
    2. Southgate E
    3. Thomson JN
    4. Brenner S
    (1986) The structure of the nervous system of the nematode Caenorhabditis elegans
    Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 314:1–340.
    https://doi.org/10.1098/rstb.1986.0056

Article and author information

Author details

  1. Michael Hendricks

    Michael Hendricks is in the Department of Biology, McGill University, Montreal, Canada

    For correspondence
    michael.hendricks@mcgill.ca
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3408-3858

Publication history

  1. Version of Record published: August 3, 2021 (version 1)

Copyright

© 2021, Hendricks

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 664
    Page views
  • 46
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Michael Hendricks
(2021)
Behavior: C. elegans does a spit take
eLife 10:e71813.
https://doi.org/10.7554/eLife.71813

Further reading

    1. Neuroscience
    Niraja Ramesh, Marc Escher ... Stephan J Sigrist
    Research Article

    We still face fundamental gaps in understanding how molecular plastic changes of synapses intersect with circuit operation to define behavioral states. Here we show that an antagonism between two conserved regulatory proteins, Spinophilin (Spn) and Syd-1, controls presynaptic long-term plasticity and the maintenance of olfactory memories in Drosophila. While Spn mutants could not trigger nanoscopic active zone remodeling under homeostatic challenge and failed to stably potentiate neurotransmitter release, concomitant reduction of Syd-1 rescued all these deficits. The Spn/Syd-1 antagonism converged on active zone close F-actin, and genetic or acute pharmacological depolymerization of F-actin rescued the Spn deficits by allowing access to synaptic vesicle release sites. Within the intrinsic mushroom body neurons, the Spn/Syd-1 antagonism specifically controlled olfactory memory stabilization but not initial learning. Thus, this evolutionarily conserved protein complex controls behaviorally relevant presynaptic long-term plasticity, also observed in the mammalian brain but still enigmatic concerning its molecular mechanisms and behavioral relevance.

    1. Computational and Systems Biology
    2. Neuroscience
    Huu Hoang, Shinichiro Tsutsumi ... Keisuke Toyama
    Research Article Updated

    Cerebellar climbing fibers convey diverse signals, but how they are organized in the compartmental structure of the cerebellar cortex during learning remains largely unclear. We analyzed a large amount of coordinate-localized two-photon imaging data from cerebellar Crus II in mice undergoing ‘Go/No-go’ reinforcement learning. Tensor component analysis revealed that a majority of climbing fiber inputs to Purkinje cells were reduced to only four functional components, corresponding to accurate timing control of motor initiation related to a Go cue, cognitive error-based learning, reward processing, and inhibition of erroneous behaviors after a No-go cue. Changes in neural activities during learning of the first two components were correlated with corresponding changes in timing control and error learning across animals, indirectly suggesting causal relationships. Spatial distribution of these components coincided well with boundaries of Aldolase-C/zebrin II expression in Purkinje cells, whereas several components are mixed in single neurons. Synchronization within individual components was bidirectionally regulated according to specific task contexts and learning stages. These findings suggest that, in close collaborations with other brain regions including the inferior olive nucleus, the cerebellum, based on anatomical compartments, reduces dimensions of the learning space by dynamically organizing multiple functional components, a feature that may inspire new-generation AI designs.