Double dissociation of the requirement for GluN2B- and GluN2A-containing NMDA receptors in the destabilization and restabilization of a reconsolidating memory

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Milton, AL 
Ratano, P 
Gregory, BL 
Dumbreck, JK 

Signaling at NMDA receptors (NMDARs) is known to be important for memory reconsolidation, but while most studies show that NMDAR antagonists prevent memory restabilization and produce amnesia, others have shown that GluN2B-selective NMDAR antagonists prevent memory destabilization, protecting the memory. These apparently paradoxical, conflicting data provide an opportunity to define more precisely the requirement for different NMDAR subtypes in the mechanisms underlying memory reconsolidation and to further understand the contribution of glutamatergic signaling to this process. Here, using rats with fully consolidated pavlovian auditory fear memories, we demonstrate a double dissociation in the requirement for GluN2B-containing and GluN2A-containing NMDARs within the basolateral amygdala in the memory destabilization and restabilization processes, respectively. We further show a double dissociation in the mechanisms underlying memory retrieval and memory destabilization, since AMPAR antagonism prevented memory retrieval while still allowing the destabilization process to occur. These data demonstrate that glutamatergic signaling mechanisms within the basolateral amygdala differentially and dissociably mediate the retrieval, destabilization, and restabilization of previously consolidated fear memories.

Amygdala, Animals, Anisomycin, Association Learning, Excitatory Amino Acid Antagonists, Fear, Male, Memory, Piperidines, Protein Synthesis Inhibitors, Quinoxalines, Rats, Receptors, N-Methyl-D-Aspartate
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Journal of Neuroscience
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Society for Neuroscience
Medical Research Council (G1002231)
Medical Research Council (G0001354)
This work was supported by UK Medical Research Council (MRC) Programme Grant 9536855 to B.J.E. and was conducted in the Behavioural and Clinical Neuroscience Institute (BCNI), an initiative jointly funded by the MRC and the Wellcome Trust. A.L.M. was supported by a BCNI lectureship, E.M. was supported by a Royal Society Newton International Fellowship, and B.L.G. by a Prior Scholarship from St. John's College, Cambridge.