Behavioral stress enhances hippocampal CA1 long-term depression through the blockade of the glutamate uptake

Chih Hao Yang, Chiung Chun Huang, Kuei Sen Hsu

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164 Citations (Scopus)


Behavioral stress has been shown to enhance long-term depression (LTD) in the CA1 region of the hippocampus, but the underlying mechanisms remain unclear. In the present study, we found that selectively blocking NR2B-containing NMDA receptors (NMDARs) abolishes the induction of LTD by prolonged low-frequency stimulation (LFS) in slices from stressed animals. Additionally, there is no need to activate NR2A-containing or synaptic NMDARs to induce this LTD, suggesting that LTD observed in slices from stressed animals is triggered primarily by extrasynaptic NMDAR activation. In contrast, stress has no effect on LTD induced by either a brief bath application of NMDA or a combination of LFS with the glutamate-uptake inhibitor DL-threo-β-benzyloxyaspartate (DL-TBOA). Furthermore, saturation of LFS-induced LTD in slices from stressed animals occludes the subsequent induction of LTD by LFS in the presence of DL-TBOA. We also found that stress induces a profound decrease in the glutamate uptake in the synaptosomal fraction of the hippocampal CA1 region. These effects were prevented when the animals were given a glucocorticoid receptor antagonist, 11β,17β-11[4-(dimethylamino)phenyl]-17-hydroxy-17-(1- (propynyl)-estra-4,9-dien-3-one, before experiencing stress. These results suggest that the blockade of glutamate uptake is a potential mechanism underlying the stress-induced enhancement of LTD and point to a novel role for glutamate-uptake machinery in the regulation of synaptic plasticity induction.

Original languageEnglish
Pages (from-to)4288-4293
Number of pages6
JournalJournal of Neuroscience
Issue number17
Publication statusPublished - Apr 27 2005
Externally publishedYes


  • Glucocorticoid receptor
  • Glutamate transporter
  • Hippocampus
  • Long-term depression
  • NMDA receptor
  • Stress

ASJC Scopus subject areas

  • General Neuroscience


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