A neuropeptide-mediated stretch response links muscle contraction to changes in neurotransmitter release

Neuron. 2011 Jul 14;71(1):92-102. doi: 10.1016/j.neuron.2011.04.021.

Abstract

Although Caenorhabditis elegans has been utilized extensively to study synapse formation and function, relatively little is known about synaptic plasticity in C. elegans. We show that a brief treatment with the cholinesterase inhibitor aldicarb induces a form of presynaptic potentiation whereby ACh release at neuromuscular junctions (NMJs) is doubled. Aldicarb-induced potentiation was eliminated by mutations that block processing of proneuropeptides, by mutations inactivating a single proneuropeptide (NLP-12), and by those inactivating an NLP-12 receptor (CKR-2). NLP-12 expression is limited to a single stretch-activated neuron, DVA. Analysis of a YFP-tagged NLP-12 suggests that aldicarb stimulates DVA secretion of NLP-12. Mutations disrupting the DVA mechanoreceptor (TRP-4) decreased aldicarb-induced NLP-12 secretion and blocked aldicarb-induced synaptic potentiation. Mutants lacking NLP-12 or CKR-2 have decreased locomotion rates. Collectively, these results suggest that NLP-12 mediates a mechanosensory feedback loop that couples muscle contraction to changes in presynaptic release, thereby providing a mechanism for proprioceptive control of locomotion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcholine / metabolism
  • Aldicarb / pharmacology
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cholinesterase Inhibitors / pharmacology
  • Inhibitory Postsynaptic Potentials / genetics
  • Inhibitory Postsynaptic Potentials / physiology
  • Locomotion / physiology
  • Mechanoreceptors / metabolism*
  • Mechanoreceptors / physiology
  • Muscle Contraction / physiology*
  • Mutation
  • Neuronal Plasticity / genetics
  • Neuronal Plasticity / physiology*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Proprotein Convertase 2 / genetics
  • Receptors, CCR2 / genetics
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / genetics
  • Synaptic Transmission / physiology*
  • TRPC Cation Channels / genetics

Substances

  • Caenorhabditis elegans Proteins
  • Cholinesterase Inhibitors
  • Neuropeptides
  • Receptors, CCR2
  • TRP-4 channel, C elegans
  • TRPC Cation Channels
  • Aldicarb
  • EGL-3 proprotein convertase, C elegans
  • Proprotein Convertase 2
  • Acetylcholine