Dataset Information

Acute Effects of Drugs on Caenorhabditis elegans Movement Reveal Complex Responses and Plasticity.

ABSTRACT: Many drugs act very rapidly - they can turn on or off their targets within minutes in a whole animal. What are the acute effects of drug treatment and how does an animal respond to these? We developed a simple assay to measure the acute effects of drugs on C. elegans movement and examined the effects of a range of compounds including neuroactive drugs, toxins, environmental stresses and novel compounds on worm movement over a time period of 3 hr. We found a wide variety of acute responses. Many compounds cause rapid paralysis which may be permanent or followed by one or more recovery phases. The recoveries are not the result of some generic stress response but are specific to the drug e.g., recovery from paralysis due to a neuroactive drug requires neurotransmitter pathways whereas recovery from a metabolic inhibitor requires metabolic changes. Finally, we also find that acute responses can vary greatly across development and that there is extensive natural variation in acute responses. In summary, acute responses are sensitive probes of the ability of biological networks to respond to drug treatment and these responses can reveal the action of unexplored pathways.

SUBMITTER: Spensley M

PROVIDER: S-EPMC6118317 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

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Acute Effects of Drugs on <i>Caenorhabditis elegans</i> Movement Reveal Complex Responses and Plasticity.

Spensley Mark M Del Borrello Samantha S Pajkic Djina D Fraser Andrew G AG

G3 (Bethesda, Md.) 20180830 9

Many drugs act very rapidly - they can turn on or off their targets within minutes in a whole animal. What are the acute effects of drug treatment and how does an animal respond to these? We developed a simple assay to measure the acute effects of drugs on <i>C. elegans</i> movement and examined the effects of a range of compounds including neuroactive drugs, toxins, environmental stresses and novel compounds on worm movement over a time period of 3 hr. We found a wide variety of acute responses ...[more]

PMID: 30061375

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Project description:Sensory loss induces cross-modal plasticity, often resulting in altered performance in remaining sensory modalities. Whereas much is known about the macroscopic mechanisms underlying cross-modal plasticity, only scant information exists about its cellular and molecular underpinnings. We found that Caenorhabditis elegans nematodes deprived of a sense of body touch exhibit various changes in behavior, associated with other unimpaired senses. We focused on one such behavioral alteration, enhanced odor sensation, and sought to reveal the neuronal and molecular mechanisms that translate mechanosensory loss into improved olfactory acuity. To this end, we analyzed in mechanosensory mutants food-dependent locomotion patterns that are associated with olfactory responses and found changes that are consistent with enhanced olfaction. The altered locomotion could be reversed in adults by optogenetic stimulation of the touch receptor (mechanosensory) neurons. Furthermore, we revealed that the enhanced odor response is related to a strengthening of inhibitory AWC→AIY synaptic transmission in the olfactory circuit. Consistently, inserting in this circuit an engineered electrical synapse that diminishes AWC inhibition of AIY counteracted the locomotion changes in touch-deficient mutants. We found that this cross-modal signaling between the mechanosensory and olfactory circuits is mediated by neuropeptides, one of which we identified as FLP-20. Our results indicate that under normal function, ongoing touch receptor neuron activation evokes FLP-20 release, suppressing synaptic communication and thus dampening odor sensation. In contrast, in the absence of mechanosensory input, FLP-20 signaling is reduced, synaptic suppression is released, and this enables enhanced olfactory acuity; these changes are long lasting and do not represent ongoing modulation, as revealed by optogenetic experiments. Our work adds to a growing literature on the roles of neuropeptides in cross-modal signaling, by showing how activity-dependent neuropeptide signaling leads to specific cross-modal plastic changes in neural circuit connectivity, enhancing sensory performance.

Dataset Information

Acute Effects of Drugs on Caenorhabditis elegans Movement Reveal Complex Responses and Plasticity.

Publications

Acute Effects of Drugs on <i>Caenorhabditis elegans</i> Movement Reveal Complex Responses and Plasticity.

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