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The Journal of Neuroscience, September 1, 2001, 21(17):6889-6896
Intra-Amygdala Blockade of the NR2B Subunit of the NMDA Receptor
Disrupts the Acquisition But Not the Expression of Fear
Conditioning
Sarina M.
Rodrigues,
Glenn E.
Schafe, and
Joseph E.
LeDoux
W. M. Keck Foundation Laboratory of Neurobiology, Center for
Neural Science, New York University, New York, New York 10003
The lateral nucleus of the amygdala (LA) is an essential component
of the neural circuitry underlying Pavlovian fear conditioning. Although blockade of NMDA receptors in LA and adjacent areas
before training disrupts the acquisition of fear conditioning, blockade before testing also often disrupts the expression of fear responses. With this pattern of results, it is not possible to distinguish a
contribution of NMDA receptors to plasticity from a role in synaptic
transmission. In past studies, NMDA blockade has been achieved using
the antagonist
D,L-2-amino-5-phosphovalerate, which blocks the entire heteromeric receptor complex. The present experiments examined the effects of selective blockade of the NR2B subunit of the
NMDA receptor in LA using the selective antagonist ifenprodil. Systemic
injections of ifenprodil before training led to a dose-dependent impairment in the acquisition of auditory and contextual fear conditioning, whereas injections before testing had no effect. Intra-amygdala infusions of ifenprodil mirrored these results and, in
addition, showed that the effects are attributable to a
disruption of fear learning rather than a disruption of memory consolidation. NMDA receptors in LA are thus involved in fear conditioning, and the NR2B subunit appears to make unique contributions to the underlying plasticity.
Key words:
fear; learning; amygdala; NMDA receptor; NR2B subunit; ifenprodil
Copyright © 2001 Society for Neuroscience 0270-6474/01/21176889-08$05.00/0
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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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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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[Abstract]
[Full Text]
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|
|
|
|
|
|
|
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[Full Text]
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|
|
|
|
|
|
|
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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83(3):
803 - 834.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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23(7):
2549 - 2556.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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22(20):
9113 - 9121.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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9(4):
178 - 190.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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22(12):
5219 - 5229.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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22(12):
5239 - 5249.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Learn. Mem.,
September 1, 2001;
8(5):
229 - 242.
[Abstract]
[Full Text]
[PDF]
|
|
|
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