Retrograde amnesia for spatial memory induced by NMDA receptor-mediated long-term potentiation

V H Brun, K Ytterbo, Richard Morris, M B Moser, Edvard I Moser

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

If information is stored as distributed patterns of synaptic weights in the hippocampal formation, retention should be vulnerable to electrically induced long-term potentiation (LTP) of hippocampal synapses after learning. This prediction was tested by training animals in a spatial water maze task and then delivering bursts of high-frequency (HF) or control stimulation to the perforant path in the angular bundle. High-frequency stimulation induced LTP in the dentate gyrus and probably also at other hippocampal termination sites. Retention in a later probe test was disrupted. When the competitive NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) was administered before the high-frequency stimulation, water maze retention was unimpaired. CPP administration blocked the induction of LTP. Thus, high-frequency stimulation of hippocampal afferents disrupts memory retention only when it induces a change in the spatial pattern of synaptic weights. The NMDA receptor dependency of this retrograde amnesia is consistent with the synaptic plasticity and memory hypothesis.

Original languageEnglish
Pages (from-to)356-62
Number of pages7
JournalJournal of Neuroscience
Issue number1
Publication statusPublished - 1 Jan 2001

Keywords / Materials (for Non-textual outputs)

  • Afferent Pathways
  • Amnesia, Retrograde
  • Animals
  • Dentate Gyrus
  • Electric Stimulation
  • Electrodes, Implanted
  • Evoked Potentials
  • Excitatory Amino Acid Antagonists
  • Excitatory Postsynaptic Potentials
  • Hippocampus
  • Long-Term Potentiation
  • Male
  • Maze Learning
  • Memory Disorders
  • Neuronal Plasticity
  • Perforant Pathway
  • Piperazines
  • Rats
  • Rats, Long-Evans
  • Reaction Time
  • Receptors, N-Methyl-D-Aspartate
  • Retention (Psychology)
  • Journal Article
  • Research Support, Non-U.S. Gov't


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