Protein Translation and LTP

Science's STKE  15 Jan 2002:
Vol. 2002, Issue 115, pp. tw18
DOI: 10.1126/stke.2002.115.tw18

Synaptic plasticity that underlies learning and memory processes, such as long-term potentiation (LTP), requires the synthesis and specific localization of new proteins to facilitate changes in synaptic strength. However, it is not clear how synaptic activity controls protein translation in neurons. Tang et al. report that a translational signaling pathway involving the rapamycin-sensitive serine-threonine kinase mammalian target of rapacymcin (mTOR) and its downstream effectors, eukaryotic initiation factor-4E-binding protein and eukaryotic intiation factor-4E, are present in the cell body and dendrites of rat hippocampal neurons. These proteins were particularly enriched in postsynaptic sites. When hippocampal slices were treated with FK506, an inhibitor of rapamycin, the magnitude of late-phase LTP decreased. FK506 also inhibited the stimulatory effect of brain-derived neurotrophic growth factor on LTP, indicating that plasticity relies on rapamycin-sensitive signaling. The precise location and mechanism by which synaptic activity activates the mTOR signaling pathway during LTP has yet to be discerned.

S. J. Tang, G. Reis, H. Kang, A.-C. Gingras, N. Sonenberg, E. M. Schuman, A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus. Proc. Natl. Acad. Sci. U.S.A. 99, 467-472 (2002). [Abstract] [Full Text]