Long-term depression requires postsynaptic AMPA GluR2 receptor in adult mouse cingulate cortex

Hiroki Toyoda, Long Jun Wu, Ming Gao Zhao, Hui Xu, Zhengping Jia, Min Zhuo

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Synaptic long-term depression (LTD) is thought to be important for various brain functions such as learning, memory, and development. Although anterior cingulated cortex (ACC) has been demonstrated to contribute to learning and memory, no studies has been reported about the synaptic mechanisms for cingulate LTD. Here, we used integrative genetic, pharmacological and electrophysiological approaches to demonstrate that AMPA GluR2, but not GluR3, subunit is critical for cingulate LTD. We found that LTD was absent in adult cingulate slices of GluR2 knockout mice. Furthermore, postsynaptic injections of peptides that inhibit AMPA GluR2-PDZ interactions blocked the induction of LTD. To determine if the requirement for AMPA receptor-PDZ interaction is time-dependent, we injected the same inhibiting peptide into the postsynaptic cells 5 min after the induction of LTD. We found that LTD was not affected by the peptide, providing the first evidence that postsynaptic AMPA GluR2-mediated depression occurs rapidly (within t = 5 min). Genetic deletion of GluR3 did not affect cingulate LTD. Our results provide the first study of cingulate LTD mechanism using whole-cell patch-clamp recording in adult cortical slices and demonstrate that postsynaptic AMPA GluR2 subunit is crucial for synaptic depression in the ACC of adult mice.

Original languageEnglish (US)
Pages (from-to)336-343
Number of pages8
JournalJournal of Cellular Physiology
Issue number2
StatePublished - May 2007

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology


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