Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Morris, R., Anderson, E, Lynch, G., & Baudry, M Nature, 319(6056):774-6, 1986. abstract bibtex Recent work has shown that the hippocampus contains a class of receptors for the excitatory amino acid glutamate that are activated by N-methyl-D-aspartate (NMDA) and that exhibit a peculiar dependency on membrane voltage in becoming active only on depolarization. Blockade of these sites with the drug aminophosphonovaleric acid (AP5) does not detectably affect synaptic transmission in the hippocampus, but prevents the induction of hippocampal long-term potentiation (LTP) following brief high-frequency stimulation. We now report that chronic intraventricular infusion of D,L-AP5 causes a selective impairment of place learning, which is highly sensitive to hippocampal damage, without affecting visual discrimination learning, which is not. The L-isomer of AP5 did not produce behavioural effects. AP5 treatment also suppressed LTP in vivo. These results suggest that NMDA receptors are involved in spatial learning, and add support to the hypothesis that LTP is involved in some, but not all, forms of learning.
@Article{Morris1986,
author = {RG Morris and E Anderson and GS Lynch and M Baudry},
journal = {Nature},
title = {Selective impairment of learning and blockade of long-term potentiation by an {N}-methyl-{D}-aspartate receptor antagonist, {AP}5.},
year = {1986},
number = {6056},
pages = {774-6},
volume = {319},
abstract = {Recent work has shown that the hippocampus contains a class of receptors
for the excitatory amino acid glutamate that are activated by N-methyl-D-aspartate
(NMDA) and that exhibit a peculiar dependency on membrane voltage
in becoming active only on depolarization. Blockade of these sites
with the drug aminophosphonovaleric acid (AP5) does not detectably
affect synaptic transmission in the hippocampus, but prevents the
induction of hippocampal long-term potentiation (LTP) following brief
high-frequency stimulation. We now report that chronic intraventricular
infusion of D,L-AP5 causes a selective impairment of place learning,
which is highly sensitive to hippocampal damage, without affecting
visual discrimination learning, which is not. The L-isomer of AP5
did not produce behavioural effects. AP5 treatment also suppressed
LTP in vivo. These results suggest that NMDA receptors are involved
in spatial learning, and add support to the hypothesis that LTP is
involved in some, but not all, forms of learning.},
keywords = {Amygdala, Animals, Evaluation Studies, Hippocampus, Human, Learning, Long-Term Potentiation, Memory, Models, Neurological, Neural Pathways, Neuronal Plasticity, Support, Non-U.S. Gov't, Synapses, 2-Amino-5-phosphonovalerate, Electric Stimulation, Isomerism, Rats, Receptors, N-Methyl-D-Aspartate, Neurotransmitter, Valine, Visual Perception, 2869411},
}
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Blockade of these sites with the drug aminophosphonovaleric acid (AP5) does not detectably affect synaptic transmission in the hippocampus, but prevents the induction of hippocampal long-term potentiation (LTP) following brief high-frequency stimulation. We now report that chronic intraventricular infusion of D,L-AP5 causes a selective impairment of place learning, which is highly sensitive to hippocampal damage, without affecting visual discrimination learning, which is not. The L-isomer of AP5 did not produce behavioural effects. AP5 treatment also suppressed LTP in vivo. 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Blockade of these sites\n\twith the drug aminophosphonovaleric acid (AP5) does not detectably\n\taffect synaptic transmission in the hippocampus, but prevents the\n\tinduction of hippocampal long-term potentiation (LTP) following brief\n\thigh-frequency stimulation. We now report that chronic intraventricular\n\tinfusion of D,L-AP5 causes a selective impairment of place learning,\n\twhich is highly sensitive to hippocampal damage, without affecting\n\tvisual discrimination learning, which is not. The L-isomer of AP5\n\tdid not produce behavioural effects. AP5 treatment also suppressed\n\tLTP in vivo. 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