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

• Published in: Neuron (Cambridge, Mass.) Mass.), 2011-07, Vol.71 (1), p.92-102
• Main Authors: Hu, Zhitao, Pym, Edward C.G., Babu, Kavita, Vashlishan Murray, Amy B., Kaplan, Joshua M.
• Format: Article
• Language: English
• Subjects: Acetylcholine; Acetylcholine - secretion; Aldicarb - pharmacology; Animals; Behavior; 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; Neurons; Neuropeptides; Neuropeptides - genetics; Neuropeptides - metabolism; Peptides; Proprotein Convertase 2 - genetics; Receptors, CCR2 - genetics; Rodents; Studies; Synaptic Transmission - drug effects; Synaptic Transmission - genetics; Synaptic Transmission - physiology; TRPC Cation Channels - genetics; Worms
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2011.04.021

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. ► 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