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 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.
Department of Biological Sciences, Florida Atlantic University, Boca Raton, Florida, United States of America.
Monica G
http://orcid.org/0000-0003-2334-3578
MG
Risley
Department of Biological Sciences, Florida Atlantic University, Boca Raton, Florida, United States of America.
Stephanie P
SP
Kelly
Department of Biological Sciences, Florida Atlantic University, Boca Raton, Florida, United States of America.
Kailiang
K
Jia
Department of Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, United States of America.
Brock
B
Grill
Department of Biological Sciences, Florida Atlantic University, Boca Raton, Florida, United States of America.
Ken
K
Dawson-Scully
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