Acute synthesis of CPEB is required for plasticity of visual avoidance behavior in Xenopus

Cell Rep. 2014 Feb 27;6(4):737-47. doi: 10.1016/j.celrep.2014.01.024. Epub 2014 Feb 13.


Neural plasticity requires protein synthesis, but the identity of newly synthesized proteins generated in response to plasticity-inducing stimuli remains unclear. We used in vivo bio-orthogonal noncanonical amino acid tagging (BONCAT) with the methionine analog azidohomoalanine (AHA) combined with the multidimensional protein identification technique (MudPIT) to identify proteins that are synthesized in the tadpole brain over 24 hr. We induced conditioning-dependent plasticity of visual avoidance behavior, which required N-methyl-D-aspartate (NMDA) and Ca(2+)-permeable α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, αCaMKII, and rapid protein synthesis. Combining BONCAT with western blots revealed that proteins including αCaMKII, MEK1, CPEB, and GAD65 are synthesized during conditioning. Acute synthesis of CPEB during conditioning is required for behavioral plasticity as well as conditioning-induced synaptic and structural plasticity in the tectal circuit. We outline a signaling pathway that regulates protein-synthesis-dependent behavioral plasticity in intact animals, identify newly synthesized proteins induced by visual experience, and demonstrate a requirement for acute synthesis of CPEB in plasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning*
  • Brain / growth & development
  • Brain / metabolism*
  • Brain / physiology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Conditioning, Classical
  • Gene Expression Regulation, Developmental*
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / metabolism
  • Larva / metabolism
  • MAP Kinase Kinase 1 / genetics
  • MAP Kinase Kinase 1 / metabolism
  • Neuronal Plasticity*
  • Proteome / genetics
  • Proteome / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Visual Perception
  • Xenopus
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • mRNA Cleavage and Polyadenylation Factors / genetics
  • mRNA Cleavage and Polyadenylation Factors / metabolism*


  • Cpeb1 protein, Xenopus
  • Proteome
  • Transcription Factors
  • Xenopus Proteins
  • mRNA Cleavage and Polyadenylation Factors
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • MAP Kinase Kinase 1
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2