Off-response in ASH neurons evoked by CuSO4 requires the TRP channel OSM-9 in Caenorhabditis elegans

Wang, Wei; Xu, Zi Jing; Wu, Ya; Qin, Li Wei; Li, Z. Y.; Zheng, Weiwei

doi:10.1016/j.bbrc.2015.04.017

Cited by 20 publications

(28 citation statements)

References 30 publications

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“…This could be attributed to the effect of accumulated ROS as a result of sustained exposure to PQ3940 or to age-related deterioration of the antioxidant mechanisms4142. Moreover, it is known that Ca 2+ influx in ASH depends on transient receptor potential channels (TRPV) and voltage-gated ion channels (VGCC)2743, the physiology of which is age-dependent4445. Therefore, a potential explanation for age-related, OS-induced Ca 2+ transients modifications21 could be that the abovementioned channels are affected by chemically induced OS more as the worms age.…”

Section: Discussionmentioning

confidence: 99%

“…Using a microfluidic chip21, we delivered a hyperosmotic stimulus (glycerol) to the worm’s nose and recorded Ca 2+ transients from the ASH sensory neuron. We chose ASH, the well-studied worms’ main nociceptor2122232425262728, because it can be activated by a wide range of repellents252930, thus being especially significant for C. elegans survival and environmental perception.…”

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confidence: 99%

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Chemically induced oxidative stress affects ASH neuronal function and behavior in C. elegans

Gourgou

Chronis

2016

Sci Rep

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Oxidative stress (OS) impact on a single neuron’s function in vivo remains obscure. Using C. elegans as a model organism, we report the effect of paraquat (PQ)-induced OS on wild type worms on the function of the ASH polymodal neuron. By calcium (Ca2+) imaging, we quantified ASH activation upon stimulus delivery. PQ-treated worms displayed higher maximum depolarization (peak of the Ca2+ transients) compared to untreated animals. PQ had a similar effect on the ASH neuron response time (rising slope of the Ca2+ transients), except in very young worms. OS effect on ASH was partially abolished in vitamin C-treated worms. We performed octanol and osmotic avoidance tests, to investigate the OS effect on ASH-dependent behaviors. PQ-treated worms have enhanced avoidance behavior compared to untreated ones, suggesting that elevated ASH Ca2+ transients result in enhanced ASH-mediated behavior. The above findings suggest a possible hormetic effect of PQ, as a factor inducing mild oxidative stress. We also quantified locomotion parameters (velocity, bending amplitude), which are not mediated by ASH activation. Bending amplitude did not differ significantly between treated and untreated worms; velocity in older adults decreased. The differential effect of OS on behavioral patterns may mirror a selective impact on the organism’s neurons.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Chemically induced oxidative stress affects ASH neuronal function and behavior in C. elegans

Gourgou

Chronis

2016

Sci Rep

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“…The ASH polymodal neuron is the subject of numerous such studies (17,18,21,22), because of its key importance as a nociceptor for the worms' survival and also because it is the starting player for a plethora of downstream neuronal events. The use of microfluidic chips for the immobilization of worms and the delivery of stimuli has revealed not only the first peak in the Ca 2+ transients of the ASH neuron occurring upon stimulation (the "on" response), but also a second peak occurring upon withdrawal of the stimulus (the "off" response) (18,23,24).…”

Section: Introductionmentioning

confidence: 99%

“…The bimodal Ca 2+ currents that occur in the ASH neuron upon its stimulation are the object of several studies, which explore the connection between Ca 2+ transients, neuronal behavior (6,(23)(24)(25) and synaptic output of the ASH neuron to downstream neurons (10,18,26). In particular, the connection between Ca 2+ transients in the ASH neuron and C. elegans behavior has been the object of several studies that suggest an interesting correlation not only between the "on" response and specific behaviors (27)(28)(29), but also between the "off" response and avoidance behavior (23). This leads to the conclusion that all features of the Ca 2+ dynamics in the ASH neuron participate in finetuning the worm's rich behavioral repertoire.…”

Section: Introductionmentioning

confidence: 99%

“…In parallel, Ca 2+ transients (3) have been studied in ASH neurons in the context of different biological conditions, including aging (17,22), oxidative stress (11,21), food availability (29) and oxygen concentration (30). Extended efforts have been made to decipher the molecular players involved (3,4,23,25,31). At the same time, mathematical modeling of Ca 2+ dynamics has been performed in a variety of organisms and cells, but the literature is sparse and far from complete for mathematical modeling of Ca 2+ response in C. elegans neurons (27,32,33).…”

Section: Introductionmentioning

confidence: 99%

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A mathematical and computational model of the calcium dynamics inCaenorhabditis elegansASH sensory neuro

Mirzakhalili

Epureanu

Gourgou

2017

Preprint

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We propose a mathematical and computational model that captures the stimulusgenerated Ca 2+ transients in the C. elegans ASH sensory neuron. The model is built based on biophysical events and molecular cascades known to unfold as part of neurons' Ca 2+ homeostasis mechanism, as well as on Ca 2+ signaling events. The state of ion channels is described by their probability of being activated or inactivated, and the remaining molecular states are based on biochemically defined kinetic equations with phenomenological adjustments. We estimate the parameters of the model using experimental data of hyperosmotic stimulus-evoked Ca 2+ transients detected with a FRET sensor in young and aged worms, unstressed and exposed to oxidative stress. We use a hybrid optimization method composed of a multi-objective genetic algorithm and nonlinear least-squares to estimate the model parameters. We first obtain the model parameters for young unstressed worms. Next, we use these values of the parameters as a starting point to identify the model parameters for stressed and aged worms. We show that the model, in combination with experimental data, corroborates literature results. In addition, we demonstrate that our model can be used to predict ASH response to complex combinations of stimulation pulses. The proposed model includes for the first time the ASH Ca 2+ dynamics observed during both "on" and "off"responses. This mathematical and computational effort is the first to propose a dynamic model of the Ca 2+ transients' mechanism in C. elegans neurons, based on biochemical pathways of the cell's Ca 2+ homeostasis machinery.Key words: C. elegans, calcium dynamics, ASH neuron, aging, oxidative stress Significance StatementC. elegans is widely used as a model system for monitoring neuronal Ca 2+ transients.The ASH neuron is the subject of several such studies, primarily due to its key importance as a polymodal nociceptor. However, despite its pivotal role in C. elegans biology, and the special characteristics of its stimulus-evoked Ca2 + transients (e.g., the peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/201962 doi: bioRxiv preprint first posted online Oct. 12, 2017; "off" response), no mathematical or computational model has been developed to include special features of ASH Ca 2+ dynamics, i.e. the "off" response. The model includes for the first time the ASH Ca 2+ dynamics observed during both "on" and "off" responses, and is the first to propose a dynamical model of the C. elegans Ca 2+ transients' mechanism based on biochemical pathways of the cell's Ca 2+ homeostasis machinery.

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Neuroendocrine Regulation in the Genetic ModelC. elegans

Borghgraef

Walle

Bael

et al. 2018

Model Animals in Neuroendocrinology

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Off-response in ASH neurons evoked by CuSO4 requires the TRP channel OSM-9 in Caenorhabditis elegans

Cited by 20 publications

References 30 publications

Chemically induced oxidative stress affects ASH neuronal function and behavior in C. elegans

Chemically induced oxidative stress affects ASH neuronal function and behavior in C. elegans

A mathematical and computational model of the calcium dynamics inCaenorhabditis elegansASH sensory neuro

Neuroendocrine Regulation in the Genetic ModelC. elegans

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