N-methyl-D-aspartate receptors in the basolateral amygdala are required for both acquisition and expression of conditional fear in rats.

Three experiments examined the effects of intra-amygdaloid infusions of an N-methyl-D-aspartate (NMDA) receptor antagonist, D,L-2-amino-5-phosphonovalerate (APV), on contextual fear conditioning in rats. In Experiment 1, APV infusion into the basolateral amygdala (BLA), before training, disrupted the acquisition of contextual fear. In Experiment 2, APV produced a disruption of both the acquisition and expression of contextual fear. This blockade of contextual fear was not state dependent, not due to a shift in footshock sensitivity, and not the result of increased motor activity in APV-treated rats. In Experiment 3, fear conditioning was not affected by a posttraining APV infusion into the BLA. These results indicate that NMDA receptors in the BLA are necessary for both the acquisition and expression of Pavlovian fear conditioning to contextual cues in rats.

[1]  M. Fanselow,et al.  Differential effects of the N-methyl-D-aspartate antagonist DL-2-amino-5-phosphonovalerate on acquisition of fear of auditory and contextual cues. , 1994, Behavioral neuroscience.

[2]  M. Gallagher,et al.  Taste-potentiated odor conditioning: impairment produced by infusion of an N-methyl-D-aspartate antagonist into basolateral amygdala. , 1995, Behavioral neuroscience.

[3]  M. Fanselow,et al.  Contextual conditioning with massed versus distributed unconditional stimuli in the absence of explicit conditional stimuli. , 1988, Journal of experimental psychology. Animal behavior processes.

[4]  Joseph E LeDoux,et al.  Fear conditioning enhances short-latency auditory responses of lateral amygdala neurons: Parallel recordings in the freely behaving rat , 1995, Neuron.

[5]  E. W. Kairiss,et al.  Long-term synaptic potentiation. , 1988, Science.

[6]  Mechanisms responsible for reduced contextual conditioning with massed unsignaled unconditional stimuli. , 1993, Journal of experimental psychology. Animal behavior processes.

[7]  R. Nicoll,et al.  Tonic activation of NMDA receptors by ambient glutamate enhances excitability of neurons. , 1989, Science.

[8]  M. Fanselow.  Associations and Memories: The Role of NMDA Receptors and Long-Term Potentiation , 1993 .

[9]  M. Fanselow,et al.  Retrograde abolition of conditional fear after excitotoxic lesions in the basolateral amygdala of rats: absence of a temporal gradient. , 1996, Behavioral neuroscience.

[10]  J. D. McGaugh,et al.  Memory of rats with amygdala lesions induced 30 days after footshock-motivated escape training reflects degree of original training. , 1994, Behavioral neuroscience.

[11]  Joseph E LeDoux,et al.  Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. , 1992, Behavioral neuroscience.

[12]  S. Kelso,et al.  Hebbian synapses in hippocampus. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Joseph E LeDoux.  Emotion: clues from the brain. , 1995, Annual review of psychology.

[14]  M. Gabriel,et al.  Basolateral amygdaloid multi-unit neuronal correlates of discriminative avoidance learning in rabbits , 1991, Brain Research.

[15]  M. Fanselow,et al.  The Amygdala and Fear Conditioning: Has the Nut Been Cracked? , 1996, Neuron.

[16]  M. Davis,et al.  N-methyl-D-aspartate lesions of the lateral and basolateral nuclei of the amygdala block fear-potentiated startle and shock sensitization of startle. , 1992, Behavioral neuroscience.

[17]  P. Bellgowan,et al.  Effects of muscimol applied to the basolateral amygdala on acquisition and expression of contextual fear conditioning in rats. , 1994, Behavioral neuroscience.

[18]  G. Collingridge,et al.  Excitatory amino acids in synaptic transmission in the Schaffer collateral‐commissural pathway of the rat hippocampus. , 1983, The Journal of physiology.

[19]  M. Fanselow,et al.  N-methyl-D-aspartate receptor antagonist APV blocks acquisition but not expression of fear conditioning. , 1991, Behavioral neuroscience.

[20]  M. Fanselow,et al.  Acquisition of contextual Pavlovian fear conditioning is blocked by application of an NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid to the basolateral amygdala. , 1994, Behavioral neuroscience.

[21]  M. Baudry,et al.  Effects of the novel NMDA receptor antagonist, CGP 39551, on field potentials and the induction and expression of LTP in the dentate gyrus in vivo , 1992, Synapse.

[22]  F. Helmstetter,et al.  The amygdala is essential for the expression of conditional hypoalgesia. , 1992, Behavioral neuroscience.

[23]  Intra-amygdala infusion of the N-methyl-D-aspartate receptor antagonist AP5 blocks acquisition but not expression of fear-potentiated startle to an auditory conditioned stimulus. , 1992, Behavioral neuroscience.

[24]  I. Izquierdo,et al.  Amnesia by post-training infusion of glutamate receptor antagonists into the amygdala, hippocampus, and entorhinal cortex. , 1992, Behavioral and neural biology.

[25]  M. Davis,et al.  Involvement of the central nucleus and basolateral complex of the amygdala in fear conditioning measured with fear-potentiated startle in rats trained concurrently with auditory and visual conditioned stimuli , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[26]  Joseph E LeDoux,et al.  Synaptic plasticity in fear conditioning circuits: induction of LTP in the lateral nucleus of the amygdala by stimulation of the medial geniculate body , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[27]  Michael Davis,et al.  Neurotransmission in the rat amygdala related to fear and anxiety , 1994, Trends in Neurosciences.

[28]  T. Robbins,et al.  Intra-amygdala infusion of the N-methyl-D-aspartate receptor antagonist AP5 impairs acquisition but not performance of discriminated approach to an appetitive CS. , 1994, Behavioral and neural biology.

[29]  E. W. Kairiss,et al.  Long‐Term synaptic potentiation in the amygdala , 1990, Synapse.

[30]  Michael Davis,et al.  Blocking of acquisition but not expression of conditioned fear-potentiated startle by NMDA antagonists in the amygdala , 1990, Nature.

[31]  M. Fanselow,et al.  Synaptic plasticity in the basolateral amygdala induced by hippocampal formation stimulation in vivo , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[33]  J. D. McGaugh,et al.  Effects of intra-amygdala injections of NMDA receptor antagonists on acquisition and retention of inhibitory avoidance , 1992, Brain Research.

[34]  M. Davis,et al.  Pre- and posttraining infusion of N-methyl-D-aspartate receptor antagonists into the amygdala impair memory in an inhibitory avoidance task. , 1994, Behavioral neuroscience.