Perisynaptic GluR2-lacking AMPA receptors control the reversibility of synaptic and spines modifications

Yunlei Yang, Xiao Bin Wang, Qiang Zhou

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

How persistent synaptic and spine modification is achieved is essential to our understanding of developmental refinement of neural circuitry and formation of memory. Within a short period after their induction, both types of modifications can either be stabilized or reversed, but how this reversibility is controlled is largely unknown. We have shown previously that AMPA receptors (AMPARs) are delivered to perisynaptic regions after the induction of long-term potentiation (LTP) but are absent from perisynaptic regions after the full expression of LTP. Here, we report that perisynaptic AMPARs are GluR2-lacking and they translocate to synapses in a protein kinase C (PKC)-dependent manner. Once entering synapses, these AMPARs quickly switch to GluR2-containing in an activity-dependent manner. Absence of postinduction activity or blocking interactions between GluR2 and NSF, or GluR2 and GRIP/PICK1 results in LTP mediated by GluR2-lacking AMPARs. However, these synaptic GluR2-lacking AMPARs are not sufficient to allow reversibility of LTP. Onthe other hand, postsynaptic inhibition of PKC activity holds AMPARs at perisynaptic regions. As long as perisynaptic AMPARs are present, both LTP and spine expansion remain labile: they can be reverted to the baseline state together with removal of perisynaptic AMPARs, or they can enter a stabilized state of persistent increase together with synaptic incorporation of perisynaptic AMPARs. Thus, perisynaptic GluR2-lacking AMPARs play a critical role in controlling the reversibility of both synaptic and spine modifications.

Original languageEnglish (US)
Pages (from-to)11999-12004
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number26
DOIs
StatePublished - Jun 29 2010
Externally publishedYes

Keywords

  • Dendritic spine
  • Long-term potentiation
  • Two-photon imaging

ASJC Scopus subject areas

  • General

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