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Cellular and systems mechanisms of memory strength as a constraint on auditory fear reconsolidation

Nature Neuroscience volume 12, pages 905–912 (2009)Cite this article

Abstract

Memory reconsolidation has been demonstrated in various tasks and species, suggesting it is a fundamental process. However, there are experimental parameters that can inhibit reconsolidation from occurring (boundary conditions). These conditions and their mechanisms remain poorly defined. Here, we characterize the ability of strong training to inhibit reconsolidation at the behavioral, systems and molecular levels. We demonstrate that strong memories in rats initially are resistant to reconsolidation, but after sufficient time will undergo reconsolidation, suggesting that boundary conditions can be transient. At the systems level, we show that the hippocampus is necessary for inhibiting reconsolidation in the amygdala. At the molecular level, we demonstrate that NR2B NMDA-receptor subunits which are critical for the induction of reconsolidation of auditory memories in the amygdala, are downregulated only under conditions when strong memories do not undergo reconsolidation. This suggests that one molecular mechanism for mediating boundary conditions is through downregulation of reconsolidation induction mechanisms.

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Figure 1: Strong auditory fear memories are insensitive to anisomycin 2 d after training.
Figure 2: Alternative reactivation protocols are not sufficient to make the strong auditory fear memories sensitive to anisomycin.
Figure 3: Strong memories undergo reconsolidation at 30 and 60 d, but not 7 d, after training.
Figure 4: Pretraining dorsal hippocampus lesions cause strong fear memory to undergo reconsolidation in the LBA.
Figure 5: NR2B-subunit abundance is inversely related to the ability of strong memories to undergo reconsolidation over time.
Figure 6: Pretraining dorsal hippocampus lesions prevent the downregulation of NR2B in strongly trained rats.

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Acknowledgements

We thank S. Kusher for detailed suggestions and comments on the manuscript. We thank various people in the lab who have helped us with these experiments. L.d.O.A. was supported by the Brazilian Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. The study was supported by Natural Sciences and Engineering Research Council (Canada), Canadian Institutes of Health Research, Canada Foundation for Innovation, Volkswagen Foundation and E.W.R. Steacie Memorial Fellowship.

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Authors and Affiliations

  1. Department of Psychology, McGill University, Montreal, Quebec, Canada

    Szu-Han Wang, Lucas de Oliveira Alvares & Karim Nader

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  1. Szu-Han Wang
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Contributions

K.N. and S.-H.W. designed and developed this study. S.-H.W. conducted the behavioral, pharmacological, lesion and immunohistochemical experiments, performed the statistical and histological analyses and wrote the paper with K.N. L.d.O.A. conducted the western blot and lesion with extinction experiments and performed related data analyses. K.N. supervised this project.

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Correspondence to Karim Nader.

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Wang, SH., de Oliveira Alvares, L. & Nader, K. Cellular and systems mechanisms of memory strength as a constraint on auditory fear reconsolidation. Nat Neurosci 12, 905–912 (2009). https://doi.org/10.1038/nn.2350

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