title: Neuropeptides amplify and focus the monoaminergic inhibition of nociception in Caenorhabditis elegans.
abstract: Monoamines and neuropeptides interact to modulate most behaviors. To better understand these interactions, we have defined the roles of tyramine (TA), octopamine, and neuropeptides in the inhibition of aversive behavior in Caenorhabditis elegans. TA abolishes the serotonergic sensitization of aversive behavior mediated by the two nociceptive ASH sensory neurons and requires the expression of the adrenergic-like, Gαq-coupled, TA receptor TYRA-3 on inhibitory monoaminergic and peptidergic neurons. For example, TA inhibition requires Gαq and Gαs signaling in the peptidergic ASI sensory neurons, with an array of ASI neuropeptides activating neuropeptide receptors on additional neurons involved in locomotory decision-making. The ASI neuropeptides required for tyraminergic inhibition are distinct from those required for octopaminergic inhibition, suggesting that individual monoamines stimulate the release of different subsets of ASI neuropeptides. Together, these results demonstrate that a complex humoral mix of monoamines is focused by more local, synaptic, neuropeptide release to modulate nociception and highlight the similarities between the tyraminergic/octopaminergic inhibition of nociception in C. elegans and the noradrenergic inhibition of nociception in mammals that also involves inhibitory peptidergic signaling.
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, Ohio 43606-3390, USA.
authors.forename: Vera
authors.initials: V
authors.lastname: Hapiak
authors.forename: Philip
authors.initials: P
authors.lastname: Summers
authors.forename: Amanda
authors.initials: A
authors.lastname: Ortega
authors.forename: Wen Jing
authors.initials: WJ
authors.lastname: Law
authors.forename: Andrew
authors.initials: A
authors.lastname: Stein
authors.forename: Richard
authors.initials: R
authors.lastname: Komuniecki
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism; D008124:Locomotion; D009479:Neuropeptides / Q000378:metabolism*; D059225:Nociception; D009655:Octopamine / Q000494:pharmacology*; D017983:Receptors, Catecholamine / Q000037:antagonists & inhibitors / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000502:physiology; D009435:Synaptic Transmission; D014439:Tyramine / Q000494:pharmacology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D044385:GTP-Binding Protein alpha Subunits; D009479:Neuropeptides; D017983:Receptors, Catecholamine; C558837:tyramine receptor 3, C elegans; D009655:Octopamine; D014439:Tyramine