Input- and subunit-specific AMPA receptor trafficking underlying long-term potentiation at hippocampal CA3 synapses

Wataru Kakegawa, Keisuke Tsuzuki, Yukari Yoshida, Kimihiko Kameyama, Seiji Ozawa

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Hippocampal CA3 pyramidal neurons receive synaptic inputs from both mossy fibres (MFs) and associational fibres (AFs). Long-term potentiation (LTP) at these synapses differs in its induction sites and N-methyl-D-aspartate receptor (NMDAR) dependence. Most evidence favours the presynaptic and postsynaptic mechanisms for induction of MF LTP and AF LTP, respectively. This implies that molecular and functional properties differ between MF and AF synapses at both presynaptic and postsynaptic sites. In this study, we focused on the difference in the postsynaptic trafficking of α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptors (AMPARs) between these synapses. To trace the subunit-specific trafficking of AMPARs at each synapse, GluR1 and GluR2 subunits were introduced into CA3 pyramidal neurons in hippocampal organotypic cultures using the Sindbis viral expression system. The electrophysiologically-tagged GluR2 AMPARs, produced by the viral-mediated transfer of the unedited form of GluR2 (GluR2Q), were inserted into both MF and AF postsynaptic sites in a neuronal activity-independent manner. Endogenous Ca2+-impermeable AMPARs at these synapses were replaced with exogenous Ca2+-permeable receptors, and Ca2+ influx via the newly expressed postsynaptic AMPARs induced NMDAR-independent LTP at AF synapses. In contrast, no GluR1 AMPAR produced by the gene transfer was constitutively incorporated into AF postsynaptic sites, and only a small amount into MF postsynaptic sites. The synaptic trafficking of GluR1 AMPARs was triggered by the activity of Ca2+/calmodulin- dependent kinase II or high-frequency stimulation to induce LTP at AF synapses, but not at MF synapses. These results indicate that MF and AF postsynaptic sites possess distinct properties for AMPAR trafficking in CA3 pyramidal neurons.

Original languageEnglish
Pages (from-to)101-110
Number of pages10
JournalEuropean Journal of Neuroscience
Volume20
Issue number1
DOIs
Publication statusPublished - 2004 Jul

Fingerprint

AMPA Receptors
Long-Term Potentiation
Synapses
Acids
Pyramidal Cells
N-Methyl-D-Aspartate Receptors
Calcium-Calmodulin-Dependent Protein Kinases

Keywords

  • AMPA
  • CA3
  • GluR1
  • GluR2
  • LTP

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Input- and subunit-specific AMPA receptor trafficking underlying long-term potentiation at hippocampal CA3 synapses. / Kakegawa, Wataru; Tsuzuki, Keisuke; Yoshida, Yukari; Kameyama, Kimihiko; Ozawa, Seiji.

In: European Journal of Neuroscience, Vol. 20, No. 1, 07.2004, p. 101-110.

Research output: Contribution to journalArticle

Kakegawa, Wataru ; Tsuzuki, Keisuke ; Yoshida, Yukari ; Kameyama, Kimihiko ; Ozawa, Seiji. / Input- and subunit-specific AMPA receptor trafficking underlying long-term potentiation at hippocampal CA3 synapses. In: European Journal of Neuroscience. 2004 ; Vol. 20, No. 1. pp. 101-110.
@article{6095692ee7d14e0086250df36860f507,
title = "Input- and subunit-specific AMPA receptor trafficking underlying long-term potentiation at hippocampal CA3 synapses",
abstract = "Hippocampal CA3 pyramidal neurons receive synaptic inputs from both mossy fibres (MFs) and associational fibres (AFs). Long-term potentiation (LTP) at these synapses differs in its induction sites and N-methyl-D-aspartate receptor (NMDAR) dependence. Most evidence favours the presynaptic and postsynaptic mechanisms for induction of MF LTP and AF LTP, respectively. This implies that molecular and functional properties differ between MF and AF synapses at both presynaptic and postsynaptic sites. In this study, we focused on the difference in the postsynaptic trafficking of α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptors (AMPARs) between these synapses. To trace the subunit-specific trafficking of AMPARs at each synapse, GluR1 and GluR2 subunits were introduced into CA3 pyramidal neurons in hippocampal organotypic cultures using the Sindbis viral expression system. The electrophysiologically-tagged GluR2 AMPARs, produced by the viral-mediated transfer of the unedited form of GluR2 (GluR2Q), were inserted into both MF and AF postsynaptic sites in a neuronal activity-independent manner. Endogenous Ca2+-impermeable AMPARs at these synapses were replaced with exogenous Ca2+-permeable receptors, and Ca2+ influx via the newly expressed postsynaptic AMPARs induced NMDAR-independent LTP at AF synapses. In contrast, no GluR1 AMPAR produced by the gene transfer was constitutively incorporated into AF postsynaptic sites, and only a small amount into MF postsynaptic sites. The synaptic trafficking of GluR1 AMPARs was triggered by the activity of Ca2+/calmodulin- dependent kinase II or high-frequency stimulation to induce LTP at AF synapses, but not at MF synapses. These results indicate that MF and AF postsynaptic sites possess distinct properties for AMPAR trafficking in CA3 pyramidal neurons.",
keywords = "AMPA, CA3, GluR1, GluR2, LTP",
author = "Wataru Kakegawa and Keisuke Tsuzuki and Yukari Yoshida and Kimihiko Kameyama and Seiji Ozawa",
year = "2004",
month = "7",
doi = "10.1111/j.1460-9568.2004.03461.x",
language = "English",
volume = "20",
pages = "101--110",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Input- and subunit-specific AMPA receptor trafficking underlying long-term potentiation at hippocampal CA3 synapses

AU - Kakegawa, Wataru

AU - Tsuzuki, Keisuke

AU - Yoshida, Yukari

AU - Kameyama, Kimihiko

AU - Ozawa, Seiji

PY - 2004/7

Y1 - 2004/7

N2 - Hippocampal CA3 pyramidal neurons receive synaptic inputs from both mossy fibres (MFs) and associational fibres (AFs). Long-term potentiation (LTP) at these synapses differs in its induction sites and N-methyl-D-aspartate receptor (NMDAR) dependence. Most evidence favours the presynaptic and postsynaptic mechanisms for induction of MF LTP and AF LTP, respectively. This implies that molecular and functional properties differ between MF and AF synapses at both presynaptic and postsynaptic sites. In this study, we focused on the difference in the postsynaptic trafficking of α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptors (AMPARs) between these synapses. To trace the subunit-specific trafficking of AMPARs at each synapse, GluR1 and GluR2 subunits were introduced into CA3 pyramidal neurons in hippocampal organotypic cultures using the Sindbis viral expression system. The electrophysiologically-tagged GluR2 AMPARs, produced by the viral-mediated transfer of the unedited form of GluR2 (GluR2Q), were inserted into both MF and AF postsynaptic sites in a neuronal activity-independent manner. Endogenous Ca2+-impermeable AMPARs at these synapses were replaced with exogenous Ca2+-permeable receptors, and Ca2+ influx via the newly expressed postsynaptic AMPARs induced NMDAR-independent LTP at AF synapses. In contrast, no GluR1 AMPAR produced by the gene transfer was constitutively incorporated into AF postsynaptic sites, and only a small amount into MF postsynaptic sites. The synaptic trafficking of GluR1 AMPARs was triggered by the activity of Ca2+/calmodulin- dependent kinase II or high-frequency stimulation to induce LTP at AF synapses, but not at MF synapses. These results indicate that MF and AF postsynaptic sites possess distinct properties for AMPAR trafficking in CA3 pyramidal neurons.

AB - Hippocampal CA3 pyramidal neurons receive synaptic inputs from both mossy fibres (MFs) and associational fibres (AFs). Long-term potentiation (LTP) at these synapses differs in its induction sites and N-methyl-D-aspartate receptor (NMDAR) dependence. Most evidence favours the presynaptic and postsynaptic mechanisms for induction of MF LTP and AF LTP, respectively. This implies that molecular and functional properties differ between MF and AF synapses at both presynaptic and postsynaptic sites. In this study, we focused on the difference in the postsynaptic trafficking of α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptors (AMPARs) between these synapses. To trace the subunit-specific trafficking of AMPARs at each synapse, GluR1 and GluR2 subunits were introduced into CA3 pyramidal neurons in hippocampal organotypic cultures using the Sindbis viral expression system. The electrophysiologically-tagged GluR2 AMPARs, produced by the viral-mediated transfer of the unedited form of GluR2 (GluR2Q), were inserted into both MF and AF postsynaptic sites in a neuronal activity-independent manner. Endogenous Ca2+-impermeable AMPARs at these synapses were replaced with exogenous Ca2+-permeable receptors, and Ca2+ influx via the newly expressed postsynaptic AMPARs induced NMDAR-independent LTP at AF synapses. In contrast, no GluR1 AMPAR produced by the gene transfer was constitutively incorporated into AF postsynaptic sites, and only a small amount into MF postsynaptic sites. The synaptic trafficking of GluR1 AMPARs was triggered by the activity of Ca2+/calmodulin- dependent kinase II or high-frequency stimulation to induce LTP at AF synapses, but not at MF synapses. These results indicate that MF and AF postsynaptic sites possess distinct properties for AMPAR trafficking in CA3 pyramidal neurons.

KW - AMPA

KW - CA3

KW - GluR1

KW - GluR2

KW - LTP

UR - http://www.scopus.com/inward/record.url?scp=3142762997&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3142762997&partnerID=8YFLogxK

U2 - 10.1111/j.1460-9568.2004.03461.x

DO - 10.1111/j.1460-9568.2004.03461.x

M3 - Article

VL - 20

SP - 101

EP - 110

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 1

ER -