Modulating Behavior in C. elegans Using Electroshock and Antiepileptic Drugs
The microscopic nematode Caenorhabditis elegans has emerged as a valuable model for understanding the molecular and cellular basis of neurological disorders. The worm offers important physiological similarities to mammalian models such as conserved neuron morphology, ion channels, and neurotransmitt...
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| creator | Risley, Monica G Kelly, Stephanie P Jia, Kailiang Grill, Brock Dawson-Scully, Ken |
| description | The microscopic nematode Caenorhabditis elegans has emerged as a valuable model for understanding the molecular and cellular basis of neurological disorders. The worm offers important physiological similarities to mammalian models such as conserved neuron morphology, ion channels, and neurotransmitters. While a wide-array of behavioral assays are available in C. elegans, an assay for electroshock/electroconvulsion remains absent. Here, we have developed a quantitative behavioral method to assess the locomotor response following electric shock in C. elegans. Electric shock impairs normal locomotion, and induces paralysis and muscle twitching; after a brief recovery period, shocked animals resume normal locomotion. We tested electric shock responses in loss-of-function mutants for unc-25, which encodes the GABA biosynthetic enzyme GAD, and unc-49, which encodes the GABAA receptor. unc-25 and unc-49 mutants have decreased inhibitory GABAergic transmission to muscles, and take significantly more time to recover normal locomotion following electric shock compared to wild-type. Importantly, increased sensitivity of unc-25 and unc-49 mutants to electric shock is rescued by treatment with antiepileptic drugs, such as retigabine. Additionally, we show that pentylenetetrazol (PTZ), a GABAA receptor antagonist and proconvulsant in mammalian and C. elegans seizure models, increases susceptibility of worms to electric shock. |
| doi_str_mv | 10.1371/journal.pone.0163786 |
| format | Article |
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The worm offers important physiological similarities to mammalian models such as conserved neuron morphology, ion channels, and neurotransmitters. While a wide-array of behavioral assays are available in C. elegans, an assay for electroshock/electroconvulsion remains absent. Here, we have developed a quantitative behavioral method to assess the locomotor response following electric shock in C. elegans. Electric shock impairs normal locomotion, and induces paralysis and muscle twitching; after a brief recovery period, shocked animals resume normal locomotion. We tested electric shock responses in loss-of-function mutants for unc-25, which encodes the GABA biosynthetic enzyme GAD, and unc-49, which encodes the GABAA receptor. unc-25 and unc-49 mutants have decreased inhibitory GABAergic transmission to muscles, and take significantly more time to recover normal locomotion following electric shock compared to wild-type. Importantly, increased sensitivity of unc-25 and unc-49 mutants to electric shock is rescued by treatment with antiepileptic drugs, such as retigabine. Additionally, we show that pentylenetetrazol (PTZ), a GABAA receptor antagonist and proconvulsant in mammalian and C. elegans seizure models, increases susceptibility of worms to electric shock.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0163786</identifier><identifier>PMID: 27668426</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Anticonvulsants ; Antiepileptic agents ; Behavior ; Binding sites ; Biology and Life Sciences ; Caenorhabditis elegans ; Drosophila ; Drugs ; Electric shock injuries ; Epilepsy ; GABA ; Glutamate decarboxylase ; Insects ; Ion channels ; Locomotion ; Mammals ; Medicine and Health Sciences ; Muscles ; Mutants ; Nematoda ; Nematodes ; Nervous system ; Nervous system diseases ; Neurological diseases ; Neurosciences ; Neurotransmitters ; Paralysis ; Pharmacology ; Physiological aspects ; Potassium ; Research and Analysis Methods ; Roundworms ; Seizures ; Seizures (Medicine) ; Shock ; Twitching ; Video recorders ; Worms ; γ-Aminobutyric acid A receptors</subject><ispartof>PloS one, 2016-09, Vol.11 (9), p.e0163786-e0163786</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Risley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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The worm offers important physiological similarities to mammalian models such as conserved neuron morphology, ion channels, and neurotransmitters. While a wide-array of behavioral assays are available in C. elegans, an assay for electroshock/electroconvulsion remains absent. Here, we have developed a quantitative behavioral method to assess the locomotor response following electric shock in C. elegans. Electric shock impairs normal locomotion, and induces paralysis and muscle twitching; after a brief recovery period, shocked animals resume normal locomotion. We tested electric shock responses in loss-of-function mutants for unc-25, which encodes the GABA biosynthetic enzyme GAD, and unc-49, which encodes the GABAA receptor. unc-25 and unc-49 mutants have decreased inhibitory GABAergic transmission to muscles, and take significantly more time to recover normal locomotion following electric shock compared to wild-type. 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One</addtitle><date>2016-09-26</date><risdate>2016</risdate><volume>11</volume><issue>9</issue><spage>e0163786</spage><epage>e0163786</epage><pages>e0163786-e0163786</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The microscopic nematode Caenorhabditis elegans has emerged as a valuable model for understanding the molecular and cellular basis of neurological disorders. The worm offers important physiological similarities to mammalian models such as conserved neuron morphology, ion channels, and neurotransmitters. While a wide-array of behavioral assays are available in C. elegans, an assay for electroshock/electroconvulsion remains absent. Here, we have developed a quantitative behavioral method to assess the locomotor response following electric shock in C. elegans. Electric shock impairs normal locomotion, and induces paralysis and muscle twitching; after a brief recovery period, shocked animals resume normal locomotion. We tested electric shock responses in loss-of-function mutants for unc-25, which encodes the GABA biosynthetic enzyme GAD, and unc-49, which encodes the GABAA receptor. unc-25 and unc-49 mutants have decreased inhibitory GABAergic transmission to muscles, and take significantly more time to recover normal locomotion following electric shock compared to wild-type. Importantly, increased sensitivity of unc-25 and unc-49 mutants to electric shock is rescued by treatment with antiepileptic drugs, such as retigabine. Additionally, we show that pentylenetetrazol (PTZ), a GABAA receptor antagonist and proconvulsant in mammalian and C. elegans seizure models, increases susceptibility of worms to electric shock.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27668426</pmid><doi>10.1371/journal.pone.0163786</doi><tpages>e0163786</tpages><orcidid>https://orcid.org/0000-0003-2334-3578</orcidid><oa>free_for_read</oa></addata></record> |
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| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Anticonvulsants Antiepileptic agents Behavior Binding sites Biology and Life Sciences Caenorhabditis elegans Drosophila Drugs Electric shock injuries Epilepsy GABA Glutamate decarboxylase Insects Ion channels Locomotion Mammals Medicine and Health Sciences Muscles Mutants Nematoda Nematodes Nervous system Nervous system diseases Neurological diseases Neurosciences Neurotransmitters Paralysis Pharmacology Physiological aspects Potassium Research and Analysis Methods Roundworms Seizures Seizures (Medicine) Shock Twitching Video recorders Worms γ-Aminobutyric acid A receptors |
| title | Modulating Behavior in C. elegans Using Electroshock and Antiepileptic Drugs |
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