Retrograde amnesia for spatial memory induced by NMDA receptor-mediated long-term potentiation.
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.
Brun
V H
VH
Department of Psychology, Norwegian University of Science and Technology, 7491 Trondheim, Norway. vegard.brun@svt.ntnu.no
Ytterbo
K
K
Morris
R G
RG
Moser
M B
MB
Moser
E I
EI
D000344:Afferent Pathways / Q000502:physiology; D000648:Amnesia, Retrograde / Q000378:metabolism*; D000818:Animals; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D005071:Evoked Potentials / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000502:physiology / Q000601:surgery; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D019580:Perforant Pathway / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid