title: GABAergic synaptic plasticity during a developmentally regulated sleep-like state in C. elegans.
abstract: Approximately one-fourth of the neurons in Caenorhabditis elegans adults are born during larval development, indicating tremendous plasticity in larval nervous system structure. Larval development shows cyclical expression of sleep-like quiescent behavior during lethargus periods, which occur at larval stage transitions. We studied plasticity at the neuromuscular junction during lethargus using the acetylcholinesterase inhibitor aldicarb. The rate of animal contraction when exposed to aldicarb is controlled by the balance between excitatory cholinergic and inhibitory GABAergic input on the muscle. During lethargus, there is an accelerated rate of contraction on aldicarb. Mutant analysis and optogenetic studies reveal that GABAergic synaptic transmission is reduced during lethargus. Worms in lethargus show partial resistance to GABA(A) receptor agonists, indicating that postsynaptic mechanisms contribute to lethargus-dependent plasticity. Using genetic manipulations that separate the quiescent state from the developmental stage, we show that the synaptic plasticity is dependent on developmental time and not on the behavioral state of the animal. We propose that the synaptic plasticity regulated by a developmental clock in C. elegans is analogous to synaptic plasticity regulated by the circadian clock in other species.
authors: Department of Neurology and Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19014, USA.
authors: Nooreen S
authors: NS
authors: Dabbish
authors: David M
authors: DM
authors: Raizen
mesh_terms: D000759:Adjuvants, Anesthesia / Q000494:pharmacology; D000448:Aldicarb / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D007814:Larva; D009118:Muscimol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D010433:Pentylenetetrazole / Q000494:pharmacology; D034622:RNA Interference / Q000502:physiology; D012890:Sleep / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012978:Sodium Oxybate / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000759:Adjuvants, Anesthesia; D029742:Caenorhabditis elegans Proteins; D002800:Cholinesterase Inhibitors; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; C568367:NHR-23 protein, C elegans; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; C075912:Lin-3 protein, C elegans; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D014212:Tretinoin; D004815:Epidermal Growth Factor; D012978:Sodium Oxybate; D000448:Aldicarb; D010433:Pentylenetetrazole