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Dag.etal2023

Sep 24, 20243 min read

Dissecting the functional organization of the C. elegans serotonergic system at whole-brain scale

authors: Ugur Dag, Ijeoma Nwabudike, Di Kang, Matthew A. Gomes, Jungsoo Kim, Adam A. Atanas, Eric Bueno, Cassi Estrem, Sarah Pugliese, Ziyu Wang, Emma Towlson, Steven W. Flavell
doi: 10.1016/j.cell.2023.04.023
zotero link: Full Text

CITATION

Dag, U., Nwabudike, I., Kang, D., Gomes, M. A., Kim, J., Atanas, A. A., Bueno, E., Estrem, C., Pugliese, S., Wang, Z., Towlson, E., & Flavell, S. W. (2023). Dissecting the functional organization of the C. elegans serotonergic system at whole-brain scale. Cell, 186(12), 2574-2592.e20. https://doi.org/10.1016/j.cell.2023.04.023

ABSTRACT

Serotonin influences many aspects of animal behavior. But how serotonin acts on its diverse receptors across the brain to modulate global activity and behavior is unknown. Here, we examine how serotonin release in C. elegans alters brain-wide activity to induce foraging behaviors, like slow locomotion and increased feeding. Comprehensive genetic analyses identify three core serotonin receptors (MOD-1, SER-4, and LGC-50) that induce slow locomotion upon serotonin release and others (SER-1, SER-5, and SER-7) that interact with them to modulate this behavior. SER-4 induces behavioral responses to sudden increases in serotonin release, whereas MOD-1 induces responses to persistent release. Whole-brain imaging reveals widespread serotonin-associated brain dynamics, spanning many behavioral networks. We map all sites of serotonin receptor expression in the connectome, which, together with synaptic connectivity, helps predict which neurons show serotonin-associated activity. These results reveal how serotonin acts at defined sites across a connectome to modulate brain-wide activity and behavior.

permanent notes

fleeting notes

  • there are three pairs of serotonergic neurons

    • NSM - controls food induced behavioral changes
    • HSN - controls egg laying. located in the midbody
    • ADF - ??

  • optogenetically activated NSM with Chrimson

    • decreased velocity, and head movements
    • increased feeding (called pharyngeal pumping)
    • speed decreased with respect to intensity and length of opto stim

  • crossed the NSM:: Chr to single mutants for each of the 6 serotonin receptors

    • each one showed decreased response to opto stim - suggesting all are important for the behavior

  • then crossed to mutants that only had 1 of the receptors

    • worms with only intact mod-1, ser-4, or lgc-50 showed slowing

  • crossed to 64 combinations of mutant backgrounds

    • mod-1, ser4, and lgc-50 are the primary receptors that drive slowing
    • the other receptors are modulatory receptors that dont have an effect on their own but cause deficits when knocked out with others

  • C. elegans have exaggerated slowing when fasted, which depends on serotonin and NSM

    • fasting enhances how mod-1 and lgc-50 receptor activation impacts neural circuit activity

  • tested effects of fasting and satiety in all 64 mutant strains

    • some interactions of receptors had exaggerated slowing, some had attenuated slowing depending on the state of the animal (hunger vs satiety)

  • expression patterns of the serotonin receptors are important for conferring their functional role

  • expressed a fluorescent reporter in each serotonin receptor gene to map expression across the brain

    • crossed to the NeuroPAL transgene
      • drives expression of 3 fluorescent proteins that are used to identify each individual neuron

  • did whole brain imaging and found that many neurons show associated activity patters with NSM

    • neurons that encode forward velocity or head curvature are more likely to be inversely correlated
    • NSM activity is associated with the inhibition of locomotion and head movement

  • neurons are more likely to be associated with NSM if they express at least one serotonin receptor

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