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GABAergic synaptic plasticity during a developmentally regulated sleep-like state in C. elegans.

Nooreen S Dabbish1, David M Raizen

  • 1Department of Neurology and Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19014, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|November 4, 2011
PubMed
Summary

During C. elegans larval development, neuromuscular junctions undergo significant plasticity, with reduced GABAergic transmission during quiescent lethargus periods. This synaptic plasticity is driven by developmental timing, not behavior.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Molecular Biology

Background:

  • The Caenorhabditis elegans nervous system exhibits plasticity during larval development, with approximately 25% of neurons forming post-embryonically.
  • Larval development includes cyclical periods of quiescent, sleep-like behavior known as lethargus, occurring at stage transitions.

Purpose of the Study:

  • To investigate synaptic plasticity at the neuromuscular junction during C. elegans lethargus.
  • To determine the mechanisms underlying changes in neuromuscular function during larval quiescent periods.

Main Methods:

  • Utilized the acetylcholinesterase inhibitor aldicarb to assess neuromuscular junction function.
  • Employed mutant analysis and optogenetics to study GABAergic synaptic transmission.

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  • Investigated postsynaptic sensitivity using GABA(A) receptor agonists.
  • Used genetic manipulations to decouple behavioral state from developmental stage.

    • Main Results:

    • Neuromuscular junctions show accelerated contraction rates upon aldicarb exposure during lethargus.
    • GABAergic synaptic transmission is significantly reduced during lethargus.
    • C. elegans in lethargus display partial resistance to GABA(A) receptor agonists, suggesting postsynaptic contributions.
    • Synaptic plasticity is dependent on developmental time, independent of the quiescent behavioral state.

    Conclusions:

    • Lethargus-associated synaptic plasticity in C. elegans involves reduced GABAergic input and altered postsynaptic sensitivity.
    • This plasticity is regulated by a developmental clock, analogous to circadian clock regulation in other species.
    • Findings highlight the dynamic nature of the nervous system during development and quiescent states.