Developmental expression of Ca2+-permeable AMPA receptors underlies depolarization-induced long-term depression at mossy fiber-CA3 pyramid synapses

Michelle T.W. Ho, Kenneth A. Pelkey, Lisa Topolnik, Ronald S. Petralia, Kogo Takamiya, Jun Xia, Richard L. Huganir, Jean Claude Lacaille, Chris J. McBain

Research output: Contribution to journalArticle


Many central excitatory synapses undergo developmental alterations in the molecular and biophysical characteristics of postsynaptic ionotropic glutamate receptors via changes in subunit composition. Concerning AMPA receptors (AMPARs), glutamate receptor 2 subunit (GluR2)-containing, Ca 2+-impermeable AMPARs (CI-AMPARs) prevail at synapses between mature principal neurons; however, accumulating evidence indicates that GluR2-lacking, Ca2+-permeable AMPARs (CP-AMPARs) contribute at these synapses early in development. Here, we used a combination of imaging and electrophysiological recording techniques to investigate potential roles for CP-AMPARs at developing hippocampal mossy fiber-CA3 pyramidal cell (MF-PYR) synapses. We found that transmission at nascent MF-PYR synapses is mediated by a mixed population of CP- and CI-AMPARs as evidenced by polyamine-dependent inwardly rectifying current-voltage (I-V) relationships, and partial philanthotoxin sensitivity of synaptic events. CP-AMPAR expression at MF-PYR synapses is transient, being limited to the first 3 postnatal weeks. Moreover, the expression of CP-AMPARs is regulated by the PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain-containing protein interacting with C kinase 1 (PICK1), because MF-PYR synapses in young PICK1 knock-out mice are philanthotoxin insensitive with linear I-V relationships. Strikingly, MF-PYR transmission via CP-AMPARs is selectively depressed during depolarization-induced long-term depression (DiLTD), a postsynaptic form of MF-PYR plasticity observed only at young MF-PYR synapses. The selective depression of CP-AMPARs during DiLTD was evident as a loss of postsynaptic CP-AMPAR-mediated Ca2+ transients in PYR spines and reduced rectification of MF-PYR synaptic currents. Preferential targeting of CP-AMPARs during DiLTD is further supported by a lack of DiLTD in young PICK1 knock-out mice. Together, these findings indicate that the transient participation of CP-AMPARs at young MF-PYR synapses dictates the developmental window to observe DiLTD.

Original languageEnglish (US)
Pages (from-to)11651-11662
Number of pages12
JournalJournal of Neuroscience
Issue number43
StatePublished - Oct 24 2007


  • Calcium
  • GluR2
  • Hippocampus
  • LTD
  • Mossy fiber
  • Synapse development

ASJC Scopus subject areas

  • Neuroscience(all)

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