Sustained CPEB-dependent local protein synthesis is required to stabilize synaptic growth for persistence of long-term facilitation in Aplysia

Neuron. 2008 Sep 25;59(6):1024-36. doi: 10.1016/j.neuron.2008.07.036.


The time course of the requirement for local protein synthesis in the stabilization of learning-related synaptic growth and the persistence of long-term memory was examined using Aplysia bifurcated sensory neuron-motor neuron cultures. We find that, following repeated pulses of serotonin (5-HT), the local perfusion of emetine, an inhibitor of protein synthesis, or a TAT-AS oligonucleotide directed against ApCPEB blocks long-term facilitation (LTF) at either 24 or 48 hr and leads to a selective retraction of newly formed sensory neuron varicosities induced by 5-HT. By contrast, later inhibition of local protein synthesis, at 72 hr after 5-HT, has no effect on either synaptic growth or LTF. These results define a specific stabilization phase for the storage of long-term memory during which newly formed varicosities are labile and require sustained CPEB-dependent local protein synthesis to acquire the more stable properties of mature varicosities required for the persistence of LTF.

Publication types

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

MeSH terms

  • Adaptation, Physiological / drug effects
  • Animals
  • Aplysia
  • Cells, Cultured
  • Emetine / pharmacology
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Memory / physiology*
  • Motor Neurons / drug effects
  • Motor Neurons / metabolism*
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / metabolism*
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / physiology*
  • Protein Synthesis Inhibitors / pharmacology
  • Serotonin / physiology
  • Synapses / drug effects
  • Synapses / metabolism
  • Time Factors


  • Protein Synthesis Inhibitors
  • Serotonin
  • Emetine