title: Serotonin and the neuropeptide PDF initiate and extend opposing behavioral states in C. elegans.
abstract: Foraging animals have distinct exploration and exploitation behaviors that are organized into discrete behavioral states. Here, we characterize a neuromodulatory circuit that generates long-lasting roaming and dwelling states in Caenorhabditis elegans. We find that two opposing neuromodulators, serotonin and the neuropeptide pigment dispersing factor (PDF), each initiate and extend one behavioral state. Serotonin promotes dwelling states through the MOD-1 serotonin-gated chloride channel. The spontaneous activity of serotonergic neurons correlates with dwelling behavior, and optogenetic modulation of the critical MOD-1-expressing targets induces prolonged dwelling states. PDF promotes roaming states through a Gαs-coupled PDF receptor; optogenetic activation of cAMP production in PDF receptor-expressing cells induces prolonged roaming states. The neurons that produce and respond to each neuromodulator form a distributed circuit orthogonal to the classical wiring diagram, with several essential neurons that express each molecule. The slow temporal dynamics of this neuromodulatory circuit supplement fast motor circuits to organize long-lasting behavioral states.
authors: Howard Hughes Medical Institute, Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior, The Rockefeller University, New York, NY 10065, USA.
authors: Steven W
authors: SW
authors: Flavell
authors: Howard Hughes Medical Institute, Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior, The Rockefeller University, New York, NY 10065, USA.
authors: Navin
authors: N
authors: Pokala
authors: Howard Hughes Medical Institute, Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior, The Rockefeller University, New York, NY 10065, USA.
authors: Evan Z
authors: EZ
authors: Macosko
authors: Howard Hughes Medical Institute, Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior, The Rockefeller University, New York, NY 10065, USA.
authors: Dirk R
authors: DR
authors: Albrecht
authors: Howard Hughes Medical Institute, Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior, The Rockefeller University, New York, NY 10065, USA.
authors: Johannes
authors: J
authors: Larsch
authors: Howard Hughes Medical Institute, Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior, The Rockefeller University, New York, NY 10065, USA. Electronic address: cori@mail.rockefeller.edu.
authors: Cornelia I
authors: CI
authors: Bargmann
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D018118:Chloride Channels / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D018118:Chloride Channels; C417030:MOD-1 protein, C elegans; D009479:Neuropeptides; C584109:PDF protein, C elegans; C530057:PDFR-1 protein, C elegans; D043562:Receptors, G-Protein-Coupled; D012701:Serotonin; D000242:Cyclic AMP
references: Gen Comp Endocrinol. 2007 Jun-Jul;152(2-3):165-75
references: 17572414
references: Neuron. 2009 Nov 25;64(4):522-36
references: 19945394
references: Nat Neurosci. 2009 Feb;12(2):229-34
references: 19079251
references: Science. 1997 Aug 8;277(5327):834-6
references: 9242616
references: Cell. 1999 Aug 6;98(3):317-27
references: 10458607
references: Nature. 2010 Jan 7;463(7277):98-102
references: 20054397
references: Nature. 2000 Feb 3;403(6769):560-4
references: 10676966
references: Neuron. 2002 Dec 19;36(6):1091-102
references: 12495624
references: Nat Neurosci. 2012 Dec;15(12):1675-82
references: 23143519
references: Neuron. 2000 Jun;26(3):619-31
references: 10896158
references: WormBook. 2008 Sep 25;:1-36
references: 18819171
references: PLoS One. 2011 Apr 20;6(4):e18766
references: 21533086
references: Nature. 2000 Nov 23;408(6811):470-5
references: 11100728
references: Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20575-82
references: 19106295
references: J Biol Chem. 2010 Dec 31;285(53):41501-8
references: 21030591
references: Nat Commun. 2012 Apr 10;3:776
references: 22491324
references: J Neurosci. 1985 Apr;5(4):956-64
references: 3981252
references: Philos Trans R Soc Lond B Biol Sci. 2010 Jul 27;365(1550):2267-78
references: 20566503
references: J Neurosci. 2012 Oct 3;32(40):13819-40
references: 23035093
references: J Biol Chem. 2008 May 30;283(22):15241-9
references: 18390545
references: Nat Genet. 2008 Nov;40(11):1375-83
references: 18953339
references: J Comp Physiol A. 1999 Jan;184(1):73-84
references: 10077864
references: Cell. 2011 Jul 22;146(2):194-207
references: 21784243
references: Neuron. 2010 Dec 22;68(6):1023-42
references: 21172606
references: Neuropsychopharmacology. 2002 Nov;27(5):869-73
references: 12431861
references: Genetics. 2012 Dec;192(4):1359-71
references: 23023001
references: PLoS Biol. 2008 Aug 5;6(8):e198
references: 18687026
references: PLoS One. 2009 Oct 23;4(10):e7584
references: 19851507
references: WormBook. 2007 Feb 20;:1-15
references: 18050501
references: Biol Psychiatry. 2005 Nov 15;58(10):831-7
references: 16018977
references: J Exp Biol. 2006 Jan;209(Pt 1):89-102
references: 16354781
references: Anesthesiology. 2011 Dec;115(6):1162-71
references: 22024713
references: Science. 1982 May 28;216(4549):1012-4
references: 6805073