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The Journal of Neuroscience, June 15, 2005, 25(24):5833-5843; doi:10.1523/JNEUROSCI.0599-05.2005

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Cellular/Molecular
Local Protein Synthesis Mediates a Rapid Increase in Dendritic Elongation Factor 1A after Induction of Late Long-Term Potentiation

Panayiotis Tsokas,1 Elizabeth A. Grace,1 PokMan Chan,2 Tao Ma,1 Stuart C. Sealfon,1,2,3 Ravi Iyengar,1,4 Emmanuel M. Landau,1,4,5 and Robert D. Blitzer1,4,5

Departments of 1Pharmacology and Biological Chemistry, 2Neurology, 3Neuroscience, and 4Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, and 5Psychiatry Service, Bronx Veterans Affairs Medical Center, Bronx, New York 10468

The maintenance of long-term potentiation (LTP) requires a brief period of accelerated protein synthesis soon after synaptic stimulation, suggesting that an early phase of enhanced translation contributes to stable LTP. The mechanism regulating protein synthesis and the location and identities of mRNAs translated are not well understood. Here, we show in acute brain slices that the induction of protein synthesis-dependent hippocampal LTP increases the expression of elongation factor 1A (eEF1A), the mRNA of which contains a 5' terminal oligopyrimidine tract. This effect is blocked by rapamycin, indicating that the increase in EF1A expression is mediated by the mammalian target of rapamycin (mTOR) pathway. We find that mRNA for eEF1A is present in pyramidal cell dendrites and that the LTP-associated increase in eEF1A expression was intact in dendrites that had been severed from their cell bodies before stimulation. eEF1A levels increased within 5 min after stimulation in a translation-dependent manner, and this effect remained stable for 3 h. These results suggest a mechanism whereby synaptic stimulation, by signaling through the mTOR pathway, produces an increase in dendritic translational capacity that contributes to LTP maintenance.

Key words: hippocampus; LTP; local protein synthesis; mTOR; eEF1A; TOP mRNA

Received Feb 14, 2005; revised May 9, 2005; accepted May 11, 2005.




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