title: Food deprivation and nicotine correct akinesia and freezing in Na(+) -leak current channel (NALCN)-deficient strains of Caenorhabditis elegans.
abstract: Mutations in various genes adversely affect locomotion in model organisms, and thus provide valuable clues about the complex processes that control movement. In Caenorhabditis elegans, loss-of-function mutations in the Na(+) leak current channel (NALCN) and associated proteins (UNC-79 and UNC-80) cause akinesia and fainting (abrupt freezing of movement during escape from touch). It is not known how defects in the NALCN induce these phenotypes or if they are chronic and irreversible. Here, we report that akinesia and freezing are state-dependent and reversible in NALCN-deficient mutants (nca-1;nca-2, unc-79 and unc-80) when additional cation channels substitute for this protein. Two main measures of locomotion were evaluated: spontaneous movement (traversal of >2 head lengths during a 5 second observation period) and the touch-freeze response (movement greater than three body bends in response to tail touch). Food deprivation for as little as 3 min stimulated spontaneous movement and corrected the touch-freeze response. Conversely, food-deprived animals that moved normally in the absence of bacteria rapidly reverted to uncoordinated movement when re-exposed to food. The effects of food deprivation were mimicked by nicotine, which suggested that acetylcholine mediated the response. Nicotine appeared to act on interneurons or motor neurons rather than directly at the neuromuscular junction because levamisole, which stimulates muscle contraction, did not correct movement. Neural circuits have been proposed to account for the effects of food deprivation and nicotine on spontaneous movement and freezing. The NALCN may play an unrecognized role in human movement disorders characterized by akinesia and freezing gait.
authors.affiliation: Department of Pharmacology, Toxicology and Neuroscience, LSU Health Sciences Center, Shreveport, LA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Bonnett
authors.forename: R
authors.initials: R
authors.lastname: Zweig
authors.forename: E J
authors.initials: EJ
authors.lastname: Aamodt
authors.forename: D S
authors.initials: DS
authors.lastname: Dwyer
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D005508:Food Deprivation; D046352:Freezing Reaction, Cataleptic; D005684:Gait; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007978:Levamisole / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects* / Q000235:genetics; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D005731:Ganglionic Stimulants; D015222:Sodium Channels; D007978:Levamisole; D009538:Nicotine; D012964:Sodium
keywords: Acetylcholine; C. elegans; Parkinson's disease; akinesia; food deprivation; freezing gait; locomotion; neural circuit; nicotine; sodium leak current channel