Acute stress causes rapid synaptic insertion of Ca2+ -permeable AMPA receptors to facilitate long-term potentiation in the hippocampus

Garry Whitehead, Jihoon Jo, Ellen L Hogg, Thomas Piers, Dong-Hyun Kim, Gillian Seaton, Heon Seok, Gilles Bru-Mercier, Gi Hoon Son, Philip Regan, Lars Hildebrandt, Eleanor Waite, Byeong-Chae Kim, Talitha L Kerrigan, Kyungjin Kim, Daniel J Whitcomb, Graham L Collingridge, Stafford L Lightman, Kwangwook Cho

Research output: Contribution to journalArticlepeer-review

78 Citations (SciVal)


The neuroendocrine response to episodes of acute stress is crucial for survival whereas the prolonged response to chronic stress can be detrimental. Learning and memory are particularly susceptible to stress with cognitive deficits being well characterized consequences of chronic stress. Although there is good evidence that acute stress can enhance cognitive performance, the mechanism(s) for this are unclear. We find that hippocampal slices, either prepared from rats following 30 min restraint stress or directly exposed to glucocorticoids, exhibit an N-methyl-d-aspartic acid receptor-independent form of long-term potentiation. We demonstrate that the mechanism involves an NMDA receptor and PKA-dependent insertion of Ca2+ -permeable AMPA receptors into synapses. These then trigger the additional NMDA receptor-independent form of LTP during high frequency stimulation.

Original languageEnglish
Pages (from-to)3753-3765
Number of pages13
JournalBrain : A Journal of Neurology
Issue numberPt 12
Publication statusPublished - 10 Dec 2013


  • Animals
  • Biotinylation
  • Calcium/metabolism
  • Dexamethasone/pharmacology
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists/pharmacology
  • Gene Expression Regulation/drug effects
  • Glucocorticoids/pharmacology
  • Hippocampus/drug effects
  • Hormone Antagonists/pharmacology
  • In Vitro Techniques
  • Long-Term Potentiation/drug effects
  • Male
  • Mifepristone/pharmacology
  • Muscarinic Antagonists/pharmacology
  • Patch-Clamp Techniques
  • Phosphorylation/drug effects
  • Rats
  • Rats, Wistar
  • Receptors, AMPA/metabolism
  • Restraint, Physical/physiology
  • Valine/analogs & derivatives


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