mTOR is essential for corticosteroid effects on hippocampal AMPA receptor function and fear memory

Hui Xiong, Frederic Casse, Yang Zhou, Ming Zhou, Zhi-Qi Xiong, Marian Joels, Stephane Martin, Harm J. Krugers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

20 Citations (Scopus)
27 Downloads (Pure)

Abstract

Glucocorticoid hormones, via activation of their receptors, promote memory consolidation, but the exact underlying mechanisms remain elusive. We examined how corticosterone regulates AMPA receptors (AMPARs), which are crucial for synaptic plasticity and memory formation. Combining a live imaging fluorescent recovery after photobleaching approach with the use of the pH-sensitive GFP-AMPAR tagging revealed that corticosterone enhances the AMPAR mobile fraction and increases synaptic trapping of AMPARs in hippocampal cells. In parallel, corticosterone-enhanced AMPAR-mediated synaptic transmission. Blocking the mammalian target of rapamycin (mTOR) pathway prevented the effects of corticosterone on both AMPAR trapping-but not on the mobile fraction-and synaptic transmission. Blocking the mTOR pathway also prevented the memory enhancing effects of corticosterone in a contextual fear-conditioning paradigm. We conclude that activation of the mTOR pathway is essential for the effects of corticosterone on synaptic trapping of AMPARs and, possibly as a consequence, fearful memory formation.

Original languageEnglish
Pages (from-to)577-583
Number of pages7
JournalLearning & Memory
Volume22
Issue number12
DOIs
Publication statusPublished - Dec-2015
Externally publishedYes

Keywords

  • SYNAPTIC PLASTICITY
  • GLUCOCORTICOID-RECEPTORS
  • BASOLATERAL AMYGDALA
  • STRESS
  • CONSOLIDATION
  • TRAFFICKING
  • ENHANCEMENT
  • SUMOYLATION
  • RAPAMYCIN
  • NEURONS

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