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Journal of Neuroscience, Vol 9, 3040-3057, Copyright © 1989 by Society for Neuroscience
Synaptic plasticity and learning: selective impairment of learning rats and blockade of long-term potentiation in vivo by the N-methyl-D- aspartate receptor antagonist AP5
RG Morris
Department of Pharmacology, University of Edinburgh Medical School, Scotland.
This paper reports a series of 5 experiments concerned with a possible role
for N-methyl-D-aspartate (NMDA) receptors in certain types of learning. The
results show that chronic intraventricular infusion of the NMDA receptor
antagonist D,L-2-amino-5-phosphonopentanoic acid (D,L- AP5) caused an
impairment of spatial but not of visual discrimination learning in rats.
Such selectivity of the learning impairment occurred despite widespread
distribution of the drug throughout the CNS. AP5 sometimes caused a
disturbance of sensorimotor function during learning, but one experiment
addressing whether this disturbance could be responsible for the spatial
learning impairment established that it was statistically independent.
Another experiment showed that AP5 did not affect the retention of
previously acquired spatial information. These behavioral effects were all
obtained with a concentration of AP5 that, in a final study, was found to
be sufficient to block hippocampal long-term potentiation (LTP) in vivo
without affecting normal synaptic transmission. Taken together, these
observations (1) implicate NMDA receptors in certain types of learning, and
(2) extend recent work showing that saturation of LTP causes an anterograde
spatial amnesia (McNaughton et al., 1986). A preliminary report of parts of
this work has been published (Morris et al., 1986a).
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|
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|
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327(2):
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|
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|
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|
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|
|
|
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121(18):
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[PDF]
|
|
|
|
|
|
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586(6):
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[Full Text]
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|
|
|
|
|
|
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21(14):
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|
|
|
|
|
|
|
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282(40):
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|
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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93(1):
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|
|
|
|
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|
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|
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279(28):
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|
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|
|
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|
|
|
|
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|
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|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
|
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297(5579):
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|
|
|
|
|
|
|
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|
|
|
|
|
|
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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August 3, 2001;
293(5531):
755a - 755.
[Full Text]
[PDF]
|
|
|
|
|
|
|
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2442 - 2450.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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J. Neurosci.,
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20(21):
8096 - 8102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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September 15, 2000;
20(18):
7080 - 7086.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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September 1, 2000;
57(1):
102 - 111.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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J. Neurosci.,
June 15, 2000;
20(12):
4732 - 4739.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. Morgan and T. J. Teyler
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August 1, 1999;
82(2):
736 - 740.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Jablonska, M. Gierdalski, M. Kossut, and J. Skangiel-Kramska
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April 1, 1999;
9(3):
222 - 231.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Bock and K. Braun
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PNAS,
March 2, 1999;
96(5):
2485 - 2490.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Allan, H. Wu, L. L. Paxton, and D. D. Savage
Prenatal Ethanol Exposure Alters the Modulation of the gamma -Aminobutyric AcidA Receptor-Gated Chloride Ion Channel in Adult Rat Offspring
J. Pharmacol. Exp. Ther.,
January 1, 1998;
284(1):
250 - 257.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. F. Yeckel and T. W. Berger
Spatial Distribution of Potentiated Synapses in Hippocampus: Dependence on Cellular Mechanisms and Network Properties
J. Neurosci.,
January 1, 1998;
18(1):
438 - 450.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Cavallaro, N. Meiri, C.-L. Yi, S. Musco, W. Ma, J. Goldberg, and D. L. Alkon
Late memory-related genes in the hippocampus revealed by RNA fingerprinting
PNAS,
September 2, 1997;
94(18):
9669 - 9673.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Holscher, R. Anwyl, and M. J. Rowan
Stimulation on the Positive Phase of Hippocampal Theta Rhythm Induces Long-Term Potentiation That Can Be Depotentiated by Stimulation on the Negative Phase in Area CA1 In Vivo
J. Neurosci.,
August 15, 1997;
17(16):
6470 - 6477.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Tonegawa, J.Z. Tsien, T.J. McHugh, P. Huerta, K.I. Blum, and M.A. Wilson
Hippocampal CA1-region-restricted Knockout of NMDAR1 Gene Disrupts Synaptic Plasticity, Place Fields, and Spatial Learning
Cold Spring Harb Symp Quant Biol,
January 1, 1996;
61(0):
225 - 238.
[Abstract]
[PDF]
|
|
|
|
|
|
|
E I Moser, M B Moser, and P Andersen
Potentiation of dentate synapses initiated by exploratory learning in rats: dissociation from brain temperature, motor activity, and arousal.
Learn. Mem.,
January 1, 1994;
1(1):
55 - 73.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. Grant, T. O'Dell, K. Karl, P. Stein, P Soriano, and E. Kandel
Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice
Science,
December 18, 1992;
258(5090):
1903 - 1910.
[Abstract]
[PDF]
|
|
|
|
|
|
|
R.G.M. Morris
Toward a Representational Hypothesis of the Role of Hippocampal Synaptic Plasticity in Spatial and Other Forms of Learning
Cold Spring Harb Symp Quant Biol,
January 1, 1990;
55(0):
161 - 173.
[Abstract]
[PDF]
|
|
|
|
|
|
|
T. Hoh, J. Beiko, F. Boon, S. Weiss, and D. P. Cain
Complex Behavioral Strategy and Reversal Learning in the Water Maze without NMDA Receptor-Dependent Long-Term Potentiation
J. Neurosci.,
May 15, 1999;
19(10):
RC2 - RC2.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
