title: DOP-2 D2-Like Receptor Regulates UNC-7 Innexins to Attenuate Recurrent Sensory Motor Neurons during C. elegans Copulation.
abstract: Neuromodulation of self-amplifying circuits directs context-dependent behavioral executions. Although recurrent networks are found throughout the Caenorhabditis elegans connectome, few reports describe the mechanisms that regulate reciprocal neural activity during complex behavior. We used C. elegans male copulation to dissect how a goal-oriented motor behavior is regulated by recurrently wired sensory-motor neurons. As the male tail presses against the hermaphrodite's vulva, cholinergic and glutamatergic reciprocal innervations of post cloaca sensilla (PCS) neurons (PCA, PCB, and PCC), hook neurons (HOA, HOB), and their postsynaptic sex muscles execute rhythmic copulatory spicule thrusts. These repetitive spicule movements continue until the male shifts off the vulva or genital penetration is accomplished. However, the signaling mechanism that temporally and spatially restricts repetitive intromission attempts to vulva cues was unclear. Here, we report that confinement of spicule insertion attempts to the vulva is facilitated by D2-like receptor modulation of gap-junctions between PCB and the hook sensillum. We isolated a missense mutation in the UNC-7(L) gap-junction isoform, which perturbs DOP-2 signaling in the PCB neuron and its electrical partner, HOA. The glutamate-gated chloride channel AVR-14 is expressed in HOA. Our analysis of the unc-7 mutant allele indicates that when DOP-2 promotes UNC-7 electrical communication, AVR-14-mediated inhibitory signals pass from HOA to PCB. As a consequence, PCB is less receptive to be stimulated by its recurrent synaptic partner, PCA. Behavioral observations suggest that dopamine neuromodulation of UNC-7 ensures attenuation of recursive intromission attempts when the male disengages or is dislodged from the hermaphrodite genitalia.
  
  
  CONCLUSIONS
  Using C. elegans male copulation as a model, we found that the neurotransmitter dopamine stimulates D2-like receptors in two sensory circuits to terminate futile behavioral loops. The D2-like receptors promote inhibitory electrical junction activity between a chemosensory and a mechanosensory circuit. Therefore, both systems are attenuated and the animal ceases the recursive behavior.
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas 77843.
authors.forename: Paola A
authors.initials: PA
authors.lastname: Correa
authors.affiliation: Jesuit College Preparatory, Dallas, Texas 75244, and.
authors.forename: Todd
authors.initials: T
authors.lastname: Gruninger
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas 77843, Howard Hughes Medical Institute rgarcia@mail.bio.tamu.edu.
authors.forename: L René
authors.initials: LR
authors.lastname: García
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001115:Arecoline / Q000494:pharmacology; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018679:Cholinergic Agonists / Q000494:pharmacology; D003307:Copulation / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D017629:Gap Junctions / Q000187:drug effects / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000502:physiology*; D009068:Movement / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology; D009154:Mutation / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014844:Vulva / Q000166:cytology
chemical_list: D029742:Caenorhabditis elegans Proteins; D018679:Cholinergic Agonists; D008565:Membrane Proteins; D017448:Receptors, Dopamine D2; C094444:Unc-7 protein, C elegans; C477462:dop-2 protein, C elegans; D001115:Arecoline; D012243:Rhodopsin; D004298:Dopamine
keywords: D2-like receptors; copulation; dopamine signaling; gap-junctions; goal-oriented behavior; recurrent neuronal network