title: Multiple Sensory Inputs Are Extensively Integrated to Modulate Nociception in C. elegans.
abstract: Sensory inputs are integrated extensively before decision making, with altered multisensory integration being associated with disorders such as autism. We demonstrate that the two C. elegans AIB interneurons function as a biphasic switch, integrating antagonistic, tonic, and acute inputs from three distinct pairs of sensory neurons to modulate nociception. Off food, animals reverse away from a noxious stimulus. In contrast, on food or serotonin, AIB signaling is inhibited and, although animals initiate an aversive response more rapidly, they continue forward after the initial backward locomotion is complete. That is, animals continue to move forward and feed even when presented with a noxious repellant, with AIB inhibition decreasing the repellant concentration evoking a maximal response. These studies demonstrate that the AIBs serve as an integrating hub, receiving inputs from different sensory neurons to modulate locomotory decision making differentially, and highlight the utility of this model to analyze the complexities of multisensory integration.
  
  
  CONCLUSIONS
  Dysfunctional sensory signaling and perception are associated with a number of disease states, including autism spectrum disorders, schizophrenia, and anxiety. We have used the C. elegans model to examine multisensory integration at the interneuron level to better understand the modulation of this complex, multicomponent process. C. elegans responds to a repulsive odorant by first backing up and then either continuing forward or turning and moving away from the odorant. This decision-making process is modulated extensively by the activity state of the two AIB interneurons, with the AIBs integrating an array of synergistic and antagonistic glutamatergic inputs, from sensory neurons responding directly to the odorant to others responding to a host of additional environmental variables to ultimately fine tune aversive behaviors.
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, Ohio 43606, and.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Summers
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, Ohio 43606, and.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Layne
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, Ohio 43606, and.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Ortega
authors.affiliation: Department of Organismic and Evolutionary Biology, Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138.
authors.forename: Gareth P
authors.initials: GP
authors.lastname: Harris
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, Ohio 43606, and.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Bamber
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, Ohio 43606, and rkomuni@uoft02.utoledo.edu.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Komuniecki
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D002118:Calcium; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D009812:Odorants; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation / Q000009:adverse effects; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D018698:Glutamic Acid; D002118:Calcium
keywords: C. elegans; behavior; electrophysiology; sensory integration