title: Inducible and titratable silencing of Caenorhabditis elegans neurons in vivo with histamine-gated chloride channels.
abstract: Recent progress in neuroscience has been facilitated by tools for neuronal activation and inactivation that are orthogonal to endogenous signaling systems. We describe here a chemical-genetic approach for inducible silencing of Caenorhabditis elegans neurons in intact animals, using the histamine-gated chloride channel HisCl1 from Drosophila and exogenous histamine. Administering histamine to freely moving C. elegans that express HisCl1 transgenes in neurons leads to rapid and potent inhibition of neural activity within minutes, as assessed by behavior, functional calcium imaging, and electrophysiology of neurons expressing HisCl1. C. elegans does not use histamine as an endogenous neurotransmitter, and exogenous histamine has little apparent effect on wild-type C. elegans behavior. HisCl1-histamine silencing of sensory neurons, interneurons, and motor neurons leads to behavioral effects matching their known functions. In addition, the HisCl1-histamine system can be used to titrate the level of neural activity, revealing quantitative relationships between neural activity and behavioral output. We use these methods to dissect escape circuits, define interneurons that regulate locomotion speed (AVA, AIB) and escape-related omega turns (AIB), and demonstrate graded control of reversal length by AVA interneurons and DA/VA motor neurons. The histamine-HisCl1 system is effective, robust, compatible with standard behavioral assays, and easily combined with optogenetic tools, properties that should make it a useful addition to C. elegans neurotechnology.
authors.affiliation: Howard Hughes Medical Institute and Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior, The Rockefeller University, New York, NY 10065.
authors.forename: Navin
authors.initials: N
authors.lastname: Pokala
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Andrew
authors.initials: A
authors.lastname: Gordus
authors.forename: Cornelia I
authors.initials: CI
authors.lastname: Bargmann
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology*; D046210:Microfluidic Analytical Techniques; D008959:Models, Neurological; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques
chemical_list: D018118:Chloride Channels; D029721:Drosophila Proteins; C446763:ort protein, Drosophila; D006632:Histamine
keywords: avoidance behavior; chemical genetics; neural circuits; neuronal silencing