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A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus

Tang, Shao Jun and Reis, Gerald and Kang, Hyejin and Gingras, Anne-Claude and Sonenberg, Nahum and Schuman, Erin M. (2002) A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus. Proceedings of the National Academy of Sciences of the United States of America, 99 (1). pp. 467-472. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:TANpnas02

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Abstract

Many forms of long-lasting behavioral and synaptic plasticity require the synthesis of new proteins. For example, long-term potentiation (LTIP) that endures for more than an hour requires both transcription and translation. The signal-transduction mechanisms that couple synaptic events to protein translational machinery during long-lasting synaptic plasticity, however, are not well understood. One signaling pathway that is stimulated by growth factors and results in the translation of specific mRNAs includes the rapamycin-sensitive kinase mammalian target of rapamycin (mTOR, also known as FRAP and RAFT-1). Several components of this translational signaling pathway, including mTOR, eukaryotic initiation factor-4E-binding proteins 1 and 2, and eukaryotic initiation factor-4E, are present in the rat hippocampus as shown by Western blot analysis, and these proteins are detected in the cell bodies and dendrites in the hippocampal slices by immunostaining studies. In cultured hippocampal neurons, these proteins are present in dendrites and are often found near the presynaptic protein, synapsin I. At synaptic sites, their distribution completely overlaps with a postsynaptic protein, PSD-95. These observations suggest the postsynaptic localization of these proteins. Disruption of mTOR signaling by rapamycin results in a reduction of late-phase LTP expression induced by high-frequency stimulation; the early phase of LTIP is unaffected. Rapamycin also blocks the synaptic potentiation induced by brain-derived neurotrophic factor in hippocampal slices. These results demonstrate an essential role for rapamycin-sensitive signaling in the expression of two forms of synaptic plasticity that require new protein synthesis. The localization of this translational signaling pathway at postsynaptic sites may provide a mechanism that controls local protein synthesis at potentiated synapses.


Item Type:Article
Additional Information:Copyright © 2002 by the National Academy of Sciences. Communicated by Norman Davidson, California Institute of Technology, Pasadena, CA, November 12, 2001 (received for review September 17, 2001). Published online before print December 26, 2001, 10.1073/pnas.012605299. We thank Michael Tsung and Holli Weld for making cultured hippocampal neurons. E.M.S. is an Assistant Investigator of the Howard Hughes Medical Institute. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Subject Keywords:LOCAL PROTEIN-SYNTHESIS; MESSENGER-RNA; MAMMALIAN TARGET; DENDRITIC SPINES; CRITICAL PERIOD; LATE-PHASE; KINASE-B; TRANSLATION; POTENTIATION; SYNAPSES
Record Number:CaltechAUTHORS:TANpnas02
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:TANpnas02
Alternative URL:http://dx.doi.org/10.1073/pnas.012605299
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1590
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:01 Feb 2006
Last Modified:14 Nov 2014 19:19

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