Sustained CPEB-dependent local protein synthesis is required to stabilize synaptic growth for persistence of long-term facilitation in Aplysia.
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.
Miniaci
Maria Concetta
MC
Department of Neuroscience, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, 1051 Riverside Drive New York, NY 10032, USA.
Kim
Joung-Hun
JH
Puthanveettil
Sathyanarayanan V
SV
Si
Kausik
K
Zhu
Huixiang
H
Kandel
Eric R
ER
Bailey
Craig H
CH
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
D011500:Protein Synthesis Inhibitors; D012701:Serotonin; D004640:Emetine