title: Developmental Function of the PHR Protein RPM-1 Is Required for Learning in Caenorhabditis elegans.
abstract: The PAM/Highwire/RPM-1 (PHR) proteins are signaling hubs that function as important regulators of neural development. Loss of function in Caenorhabditis elegans rpm-1 and Drosophila Highwire results in failed axon termination, inappropriate axon targeting, and abnormal synapse formation. Despite broad expression in the nervous system and relatively dramatic defects in synapse formation and axon development, very mild abnormalities in behavior have been found in animals lacking PHR protein function. Therefore, we hypothesized that large defects in behavior might only be detected in scenarios in which evoked, prolonged circuit function is required, or in which behavioral plasticity occurs. Using quantitative approaches in C. elegans, we found that rpm-1 loss-of-function mutants have relatively mild abnormalities in exploratory locomotion, but have large defects in evoked responses to harsh touch and learning associated with tap habituation. We explored the nature of the severe habituation defects in rpm-1 mutants further. To address what part of the habituation circuit was impaired in rpm-1 mutants, we performed rescue analysis with promoters for different neurons. Our findings indicate that RPM-1 function in the mechanosensory neurons affects habituation. Transgenic expression of RPM-1 in adult animals failed to rescue habituation defects, consistent with developmental defects in rpm-1 mutants resulting in impaired habituation. Genetic analysis showed that other regulators of neuronal development that function in the rpm-1 pathway (including glo-4, fsn-1, and dlk-1) also affected habituation. Overall, our findings suggest that developmental defects in rpm-1 mutants manifest most prominently in behaviors that require protracted or plastic circuit function, such as learning.
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Giles
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458.
authors.forename: Karla J
authors.initials: KJ
authors.lastname: Opperman
authors.affiliation: Department of Psychology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada Brain Research Centre, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada.
authors.forename: Catharine H
authors.initials: CH
authors.lastname: Rankin
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458 bgrill@scripps.edu.
authors.forename: Brock
authors.initials: B
authors.lastname: Grill
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006185:Habituation, Psychophysiologic / Q000235:genetics; D008124:Locomotion / Q000235:genetics; D040542:Mechanotransduction, Cellular; D009154:Mutation; D009474:Neurons / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D020662:Guanine Nucleotide Exchange Factors; C409634:RPM-1 protein, C elegans
keywords: C. elegans; PHR protein; RPM-1; habituation; learning