title: Multiple excitatory and inhibitory neural signals converge to fine-tune Caenorhabditis elegans feeding to food availability.
abstract: How an animal matches feeding to food availability is a key question for energy homeostasis. We addressed this in the nematode Caenorhabditis elegans, which couples feeding to the presence of its food (bacteria) by regulating pharyngeal activity (pumping). We scored pumping in the presence of food and over an extended time course of food deprivation in wild-type and mutant worms to determine the neural substrates of adaptive behavior. Removal of food initially suppressed pumping but after 2 h this was accompanied by intermittent periods of high activity. We show pumping is fine-tuned by context-specific neural mechanisms and highlight a key role for inhibitory glutamatergic and excitatory cholinergic/peptidergic drives in the absence of food. Additionally, the synaptic protein UNC-31 [calcium-activated protein for secretion (CAPS)] acts through an inhibitory pathway not explained by previously identified contributions of UNC-31/CAPS to neuropeptide or glutamate transmission. Pumping was unaffected by laser ablation of connectivity between the pharyngeal and central nervous system indicating signals are either humoral or intrinsic to the enteric system. This framework in which control is mediated through finely tuned excitatory and inhibitory drives resonates with mammalian hypothalamic control of feeding and suggests that fundamental regulation of this basic animal behavior may be conserved through evolution from nematode to human.
authors.affiliation: *Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, United Kingdom; and Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dallière
authors.affiliation: *Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, United Kingdom; and Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Bhatla
authors.affiliation: *Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, United Kingdom; and Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Zara
authors.initials: Z
authors.lastname: Luedtke
authors.affiliation: *Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, United Kingdom; and Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Dengke K
authors.initials: DK
authors.lastname: Ma
authors.affiliation: *Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, United Kingdom; and Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Woolman
authors.affiliation: *Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, United Kingdom; and Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Walker
authors.affiliation: *Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, United Kingdom; and Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA lmhd@soton.ac.uk.
authors.forename: Lindy
authors.initials: L
authors.lastname: Holden-Dye
authors.affiliation: *Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, United Kingdom; and Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D005247:Feeding Behavior / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009479:Neuropeptides / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D009479:Neuropeptides; C107581:UNC-31 protein, C elegans; D018698:Glutamic Acid
keywords: UNC-31; behavioral plasticity; fasting; glutamate; neuropeptide