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

Shao-Jun Tang, Gerald Reis, Hyejin Kang, Anne Claude Gingras, Nahum Sonenberg, Erin M. Schuman

Research output: Contribution to journalArticle

515 Citations (Scopus)

Abstract

Many forms of long-lasting behavioral and synaptic plasticity require the synthesis of new proteins. For example, long-term potentiation (LTP) 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 LTP 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.

Original languageEnglish (US)
Pages (from-to)467-472
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number1
DOIs
StatePublished - Jan 8 2002
Externally publishedYes

Fingerprint

Neuronal Plasticity
Sirolimus
Hippocampus
Proteins
Long-Term Potentiation
Eukaryotic Initiation Factor-4E
Dendrites
Synapsins
Brain-Derived Neurotrophic Factor
Protein Biosynthesis
Synapses
Signal Transduction
Intercellular Signaling Peptides and Proteins
Carrier Proteins
Phosphotransferases
Western Blotting
Neurons

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus. / Tang, Shao-Jun; Reis, Gerald; Kang, Hyejin; Gingras, Anne Claude; Sonenberg, Nahum; Schuman, Erin M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 1, 08.01.2002, p. 467-472.

Research output: Contribution to journalArticle

Tang, Shao-Jun ; Reis, Gerald ; Kang, Hyejin ; Gingras, Anne Claude ; Sonenberg, Nahum ; Schuman, Erin M. / A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 1. pp. 467-472.
@article{5bdf24b7ebd44ace8c190127988ec820,
title = "A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus",
abstract = "Many forms of long-lasting behavioral and synaptic plasticity require the synthesis of new proteins. For example, long-term potentiation (LTP) 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 LTP 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.",
author = "Shao-Jun Tang and Gerald Reis and Hyejin Kang and Gingras, {Anne Claude} and Nahum Sonenberg and Schuman, {Erin M.}",
year = "2002",
month = "1",
day = "8",
doi = "10.1073/pnas.012605299",
language = "English (US)",
volume = "99",
pages = "467--472",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "1",

}

TY - JOUR

T1 - A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus

AU - Tang, Shao-Jun

AU - Reis, Gerald

AU - Kang, Hyejin

AU - Gingras, Anne Claude

AU - Sonenberg, Nahum

AU - Schuman, Erin M.

PY - 2002/1/8

Y1 - 2002/1/8

N2 - Many forms of long-lasting behavioral and synaptic plasticity require the synthesis of new proteins. For example, long-term potentiation (LTP) 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 LTP 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.

AB - Many forms of long-lasting behavioral and synaptic plasticity require the synthesis of new proteins. For example, long-term potentiation (LTP) 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 LTP 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.

UR - http://www.scopus.com/inward/record.url?scp=0037039358&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037039358&partnerID=8YFLogxK

U2 - 10.1073/pnas.012605299

DO - 10.1073/pnas.012605299

M3 - Article

VL - 99

SP - 467

EP - 472

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 1

ER -