A Neuropeptide-Mediated Stretch Response Links Muscle Contraction to Changes in Neurotransmitter Release

SummaryAlthough 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.

► A cholinesterase inhibitor (aldicarb) induces presynaptic potentiation
► Synaptic potentiation is mediated by a neuropeptide (NLP-12) and its receptor (CKR-2)
► Aldicarb stimulates NLP-12 release from a stretch-sensing neuron (DVA)
► The NLP-12 proprioceptive feedback loop is required to sustain high locomotion rates