Recruitment of calcium-permeable AMPA receptors during synaptic potentiation is regulated by CaM-kinase I

Eric S. Guire, Michael C. Oh, Thomas R. Soderling, Victor A. Derkach

Research output: Contribution to journalArticlepeer-review

127 Scopus citations


Ca2+-permeable AMPA receptors (CP-AMPARs) at central glutamatergic synapses are of special interest because of their unique biophysical and signaling properties that contribute to synaptic plasticity and their roles in multiple neuropathologies. However, intracellular signaling pathways that recruit synaptic CP-AMPARs are unknown, and involvement of CP-AMPARs in hippocampal region CA1 synaptic plasticity is controversial. Here, we report that intracellular infusion of active CaM-kinase I (CaMKI) into cultured hippocampal neurons enhances miniature EPSC amplitude because of recruitment of CP-AMPARs, likely from an extrasynaptic pool. The ability of CaMKI, which regulates the actin cytoskeleton, to recruit synaptic CP-AMPARs was blocked by inhibiting actin polymerization with latrunculin A. CaMK regulation of CP-AMPARs was also confirmed in hippocampal slices. CA1 long-term potentiation (LTP) after theta bursts, but not high-frequency tetani, produced a rapid, transient expression of synaptic CP-AMPARs that facilitated LTP. This component of TBS LTP was blocked by inhibition of CaM-kinase kinase (CaMKK), the upstream activator of CaMKI. Our calculations show that adding CP-AMPARs numbering <5% of existing synaptic AMPARs is sufficient to account for the potentiation observed in LTP. Thus, synaptic expression of CP-AMPARs is a very efficient mechanism for rapid enhancement of synaptic strength that depends on CaMKK/CaMKI signaling, actin dynamics, and the pattern of synaptic activity used to induce CA1 LTP.

Original languageEnglish (US)
Pages (from-to)6000-6009
Number of pages10
JournalJournal of Neuroscience
Issue number23
StatePublished - Jun 4 2008


  • AMPA receptor
  • CaM-kinase
  • Calcium
  • Hippocampus
  • LTP
  • Synaptic plasticity

ASJC Scopus subject areas

  • General Neuroscience


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