title: Sustained CPEB-dependent local protein synthesis is required to stabilize synaptic growth for persistence of long-term facilitation in Aplysia.
abstract: 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.
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, 1051 Riverside Drive New York, NY 10032, USA.
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Miniaci
authors.forename: Joung-Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Sathyanarayanan V
authors.initials: SV
authors.lastname: Puthanveettil
authors.forename: Kausik
authors.initials: K
authors.lastname: Si
authors.forename: Huixiang
authors.initials: H
authors.lastname: Zhu
authors.forename: Eric R
authors.initials: ER
authors.lastname: Kandel
authors.forename: Craig H
authors.initials: CH
authors.lastname: Bailey
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D001048:Aplysia; D002478:Cells, Cultured; D004640:Emetine / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D011500:Protein Synthesis Inhibitors; D012701:Serotonin; D004640:Emetine