Developmental regulation of hippocampal long-term depression by cofilin-mediated actin reorganization

Feng Cao, Zikai Zhou, Xingxiu Pan, Celeste Leung, Wei Xie, Graham Collingridge, Zhengping Jia

Research output: Contribution to journalArticle (Academic Journal)

5 Citations (Scopus)
319 Downloads (Pure)

Abstract

Long lasting synaptic plasticity involves both functional and morphological changes, but how these processes are molecularly linked to achieve coordinated plasticity remains poorly understood. Cofilin is a common target of multiple signaling pathways at the synapse and is required for both functional and spine plasticity, but how it is regulated is unclear. In this study, we investigate whether the involvement of cofilin in plasticity is developmentally regulated by examining the role of cofilin in hippocampal long-term depression (LTD) in both young (2 weeks) and mature (2 months) mice. We show that both total protein level of cofilin and its activation undergo significant changes as the brain matures, so that although the amount of cofilin decreases significantly in mature mice, its regulation by protein phosphorylation becomes increasingly important. Consistent with these biochemical data, we show that cofilin-mediated actin reorganization is essential for LTD in mature, but not in young mice. In contrast to cofilin, the GluA2 interactions with NSF and PICK1 appear to be required in both young and mature mice, indicating that AMPAR internalization is a common key mechamism for LTD expression regardless of the developmental stages. These results establish the temporal specificity of cofilin in LTD regulation and suggested that cofilin-mediated actin reorganization may serve as a key mechanism underling developmental regulation of synaptic and spine plasticity.
Original languageEnglish
Pages (from-to)66-75
Number of pages10
JournalNeuropharmacology
Volume112
Issue numberA
Early online date16 Aug 2016
DOIs
Publication statusPublished - Jan 2017

Keywords

  • Hippocampal LTD
  • AMPA receptor
  • NSF
  • PICK1
  • Actin
  • Cofilin
  • Developmental regulation

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