A tonically active master neuron modulates mutually exclusive motor states at two timescales

Meng, Jun; Ahamed, Tosif; Yu, Bin; Hung, Wesley; Mouridi, Sonia El; Leclercq-Blondel, Alice; Gendrel, Marie; Wang, Zezhen; Chen, Lili; Wen, Quan; Boulin, Thomas; Gao, Shangbang; Zhen, Mei

doi:10.1101/2022.04.06.487231

Cited by 6 publications

(16 citation statements)

References 146 publications

(403 reference statements)

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“…elegans motor behavior and suggest that the behavioral effects of twk-40 might be associated with its neuron-specific expression and functional differentiation of transcript isoforms. Two recent studies further analyzed TWK-40 functions in regulating the resting membrane potentials and activities of AVA and DVB neurons [ 81 , 82 ]. We also uncovered potential behavioral effects of five other K2P genes and provide genetic evidence that some K2Ps and NALCN can oppositely affect different aspects of C .…”

Section: Discussionmentioning

confidence: 99%

Differential modulation of C. elegans motor behavior by NALCN and two-pore domain potassium channels

Zhou

et al. 2022

PLoS Genet

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Two-pore domain potassium channels (K2P) are a large family of “background” channels that allow outward “leak” of potassium ions. The NALCN/UNC80/UNC79 complex is a non-selective channel that allows inward flow of sodium and other cations. It is unclear how K2Ps and NALCN differentially modulate animal behavior. Here, we found that loss of function (lf) in the K2P gene twk-40 suppressed the reduced body curvatures of C. elegans NALCN(lf) mutants. twk-40(lf) caused a deep body curvature and extended backward locomotion, and these phenotypes appeared to be associated with neuron-specific expression of twk-40 and distinct twk-40 transcript isoforms. To survey the functions of other less studied K2P channels, we examined loss-of-function mutants of 13 additional twk genes expressed in the motor circuit and detected defective body curvature and/or locomotion in mutants of twk-2, twk-17, twk-30, twk-48, unc-58, and the previously reported twk-7. We generated presumptive gain-of-function (gf) mutations in twk-40, twk-2, twk-7, and unc-58 and found that they caused paralysis. Further analyses detected variable genetic interactions between twk-40 and other twk genes, an interdependence between twk-40 and twk-2, and opposite behavioral effects between NALCN and twk-2, twk-7, or unc-58. Finally, we found that the hydrophobicity/hydrophilicity property of TWK-40 residue 159 could affect the channel activity. Together, our study identified twk-40 as a novel modulator of the motor behavior, uncovered potential behavioral effects of five other K2P genes and suggests that NALCN and some K2Ps can oppositely affect C. elegans behavior.

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Section: Discussionmentioning

confidence: 99%

Differential modulation of C. elegans motor behavior by NALCN and two-pore domain potassium channels

Zhou

et al. 2022

PLoS Genet

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“…Remarkably, our recent findings reveal that the TWK-40 K 2P channel plays a pivotal role in modulating global locomotor activity by influencing the activity of the AVA premotor interneuron ( 30 ). Specifically, animals with a loss-of-function ( lf ) mutation in twk-40 exhibit exaggerated body bends during both forward and backward movement, and more frequent and prolonged reversals.…”

Section: Introductionmentioning

confidence: 91%

A leak K+ channel TWK-40 sustains the rhythmic motor program

Yue,

Li,

et al. 2024

PNAS Nexus

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Leak potassium (K+) currents, conducted by two-pore domain K+ (K2P) channels, are critical for the stabilization of the membrane potential. The effect of K2P channels on motor rhythm remains enigmatic. We show here that the K2P TWK-40 contributes to the rhythmic defecation motor program (DMP) in Caenorhabditis elegans. Disrupting TWK-40 suppresses the expulsion defects of nlp-40 and aex-2 mutants. By contrast, a gain-of-function (gf) mutant of twk-40 significantly reduces the expulsion frequency per DMP cycle. In situ whole-cell patch clamping demonstrates that TWK-40 forms an outward current that hyperpolarize the resting membrane potential of dorsorectal ganglion ventral process B (DVB), an excitatory GABAergic motor neuron that activates expulsion muscle contraction. In addition, TWK-40 substantially contributes to the rhythmic activity of DVB. Specifically, DVB Ca2+ oscillations exhibit obvious defects in loss-of-function (lf) mutant of twk-40. Expression of TWK-40(gf) in DVB recapitulates the expulsion deficiency of the twk-40(gf) mutant, and inhibits DVB Ca2+ oscillations in both wild-type and twk-40(lf) animals. Moreover, DVB innervated enteric muscles also exhibit rhythmic Ca2+ defects in twk-40 mutants. In summary, these findings establish TWK-40 as a crucial neuronal stabilizer of DMP, linking leak K2P channels with rhythmic motor activity.

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“…Most attempts to quantify behavior focus on particular spatiotemporal scales of interest (Schwarz et al (2015); Marques et al (2018); Helms et al (2019)). Recent analysis of short timescale behaviors at high resolution has for example shed light on the neuronal circuits underlying sensorimotor integration (Meng et al (2024); Kano et al (2023); Darmohray et al (2019); Böhm et al (2016); Knafo et al (2017); Carbo-Tano et al (2023)). In contrast, the analysis of long timescale behaviors at low spatiotemporal resolution uncovered changing internal states (Ben Arous et al (2009); Fujiwara et al (2002); Flavell et al (2013); Marques et al (2020)).…”

Section: Introductionmentioning

confidence: 99%

Uncovering multiscale structure in the variability of larval zebrafish navigation

Sridhar,

Vergassola,

Marques

et al. 2024

Preprint

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Animals chain movements into long-lived motor strategies, resulting in variability that ultimately reflects the interplay between internal states and environmental cues. To reveal structure in such variability, we build models that bridges across time scales that enable a quantitative comparison of behavioral phenotypes among individuals. Applied to larval zebrafish exposed to diverse sensory cues, we uncover a hierarchy of long-lived motor strategies, dominated by changes in orientation distinguishing cruising and wandering strategies. Environmental cues induce preferences along these modes at the population level: while fish cruise in the light, they wander in response to aversive (dark) stimuli or in search for prey. Our method enables us to encode the behavioral dynamics of each individual fish in the transitions among coarse-grained motor strategies. By doing so, we uncover a hierarchical structure to the phenotypic variability that corresponds to exploration-exploitation trade-offs. Within a wide range of sensory cues, a major source of variation among fish is driven by prior and immediate exposure to prey that induces exploitation phenotypes. However, a large degree of variability is unexplained by environmental cues, pointing to hidden states that override the sensory context to induce contrasting exploration-exploitation phenotypes. Altogether, our approach extracts the timescales of motor strategies deployed during navigation, exposing undiscovered structure among individuals and pointing to internal states tuned by prior experience.

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A tonically active master neuron modulates mutually exclusive motor states at two timescales

Cited by 6 publications

References 146 publications

Differential modulation of C. elegans motor behavior by NALCN and two-pore domain potassium channels

Differential modulation of C. elegans motor behavior by NALCN and two-pore domain potassium channels

A leak K+ channel TWK-40 sustains the rhythmic motor program

Uncovering multiscale structure in the variability of larval zebrafish navigation

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