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The Journal of Neuroscience, June 1, 2001, 21(11):4116-4124
Amygdalar NMDA Receptors Are Critical for the Expression
of Multiple Conditioned Fear Responses
Hongjoo J.
Lee1,
June-Seek
Choi1,
Thomas H.
Brown1, 2, 3, and
Jeansok J.
Kim1, 3
Departments of 1 Psychology and 2 Cellular
and Molecular Physiology, and 3 Interdepartmental
Neuroscience Program, Yale University, New Haven, Connecticut
06520-8205
There is conflicting evidence regarding the issue of whether NMDA
receptors in the basolateral amygdalar complex (BLA) are critically
involved in the expression of conditioned fear. This matter was
addressed by infusing the rat BLA with
D,L-2-amino-5-phosphonovaleric acid (APV), a competitive
NMDA receptor antagonist. APV infusion into the BLA was reported to
block the expression of conditioned fear when measured by freezing but
not when measured by fear-potentiated startle response to a loud noise.
To examine this issue further, here we used multiple indices of
conditioned fear, including analgesia, 22 kHz ultrasonic vocalization
(USV), defecation, and freezing. Rats with bilateral BLA cannula
implants underwent fear conditioning consisting of 10 tone-footshock
pairings. Before context and tone fear-retention tests, animals
received intra-BLA infusions with APV (2.5 µg/side) or artificial
CSF. Both tone and context tests demonstrated that the
expression of conditioned freezing, USV, defecation, and analgesia were
significantly impaired by intra-amygdalar infusions of APV. In a second
set of experiments, intra-BLA infusions of APV markedly impaired the
normal expression of postshock fear responses during training, as
measured by freezing, USV, and defecation. Immediate postshock fear
expression was predictive of subsequent fear retention to the tone and
context when the animals were not infused. These results are consistent
with the hypothesis that amygdalar NMDA receptors participate in normal
synaptic transmission and therefore the overall functioning of the amygdala.
Key words:
learning; memory; amygdala; LTP; fear conditioning; synaptic plasticity; emotion
Copyright © 2001 Society for Neuroscience 0270-6474/01/21114116-09$05.00/0
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