title: Fragile X Mental Retardation Protein Is Required to Maintain Visual Conditioning-Induced Behavioral Plasticity by Limiting Local Protein Synthesis.
abstract: Fragile X mental retardation protein (FMRP) is thought to regulate neuronal plasticity by limiting dendritic protein synthesis, but direct demonstration of a requirement for FMRP control of local protein synthesis during behavioral plasticity is lacking. Here we tested whether FMRP knockdown in Xenopus optic tectum affects local protein synthesis in vivo and whether FMRP knockdown affects protein synthesis-dependent visual avoidance behavioral plasticity. We tagged newly synthesized proteins by incorporation of the noncanonical amino acid azidohomoalanine and visualized them with fluorescent noncanonical amino acid tagging (FUNCAT). Visual conditioning and FMRP knockdown produce similar increases in FUNCAT in tectal neuropil. Induction of visual conditioning-dependent behavioral plasticity occurs normally in FMRP knockdown animals, but plasticity degrades over 24 h. These results indicate that FMRP affects visual conditioning-induced local protein synthesis and is required to maintain the visual conditioning-induced behavioral plasticity.
  
  
  
  Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. Exaggerated dendritic protein synthesis resulting from loss of fragile X mental retardation protein (FMRP) is thought to underlie cognitive deficits in FXS, but no direct evidence has demonstrated that FMRP-regulated dendritic protein synthesis affects behavioral plasticity in intact animals. Xenopus tadpoles exhibit a visual avoidance behavior that improves with visual conditioning in a protein synthesis-dependent manner. We showed that FMRP knockdown and visual conditioning dramatically increase protein synthesis in neuronal processes. Furthermore, induction of visual conditioning-dependent behavioral plasticity occurs normally after FMRP knockdown, but performance rapidly deteriorated in the absence of FMRP. These studies show that FMRP negatively regulates local protein synthesis and is required to maintain visual conditioning-induced behavioral plasticity in vivo.
authors.affiliation: Dorris Neuroscience Center, Kellogg School of Science and Technology, The Scripps Research Institute, La Jolla, California 92037.
authors.forename: Han-Hsuan
authors.initials: HH
authors.lastname: Liu
authors.affiliation: Dorris Neuroscience Center, Kellogg School of Science and Technology, The Scripps Research Institute, La Jolla, California 92037 Cline@scripps.edu.
authors.forename: Hollis T
authors.initials: HT
authors.lastname: Cline
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001362:Avoidance Learning; D001386:Azides / Q000494:pharmacology; D050882:CREB-Binding Protein / Q000378:metabolism; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007814:Larva; D008297:Male; D009415:Nerve Net / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000235:genetics* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010775:Photic Stimulation; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology; D013477:Superior Colliculi / Q000166:cytology*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D014795:Visual Pathways / Q000187:drug effects / Q000502:physiology; D014981:Xenopus
chemical_list: D001386:Azides; D050882:CREB-Binding Protein; D051860:Fragile X Messenger Ribonucleoprotein 1; D011500:Protein Synthesis Inhibitors; D055748:SOXB1 Transcription Factors; D013096:Spermine; D014404:Tubulin; C527782:SOX2 protein, human; C096004:azidophenylspermine
keywords: Xenopus; dendritic protein synthesis; plasticity; retinotectal; visual avoidance behavior; visual conditioning