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Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval

Abstract

‘New’ memories are initially labile and sensitive to disruption before being consolidated into stable long-term memories1,2,3,4,5. Much evidence indicates that this consolidation involves the synthesis of new proteins in neurons6,7,8,9. The lateral and basal nuclei of the amygdala (LBA) are believed to be a site of memory storage in fear learning10. Infusion of the protein synthesis inhibitor anisomycin into the LBA shortly after training prevents consolidation of fear memories11. Here we show that consolidated fear memories, when reactivated during retrieval, return to a labile state in which infusion of anisomycin shortly after memory reactivation produces amnesia on later tests, regardless of whether reactivation was performed 1 or 14 days after conditioning. The same treatment with anisomycin, in the absence of memory reactivation, left memory intact. Consistent with a time-limited role for protein synthesis production in consolidation, delay of the infusion until six hours after memory reactivation produced no amnesia. Our data show that consolidated fear memories, when reactivated, return to a labile state that requires de novo protein synthesis for reconsolidation. These findings are not predicted by traditional theories of memory consolidation.

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Figure 1: Schematic representation of the amygdala at four different rostral–caudal planes.
Figure 2: A test of whether consolidated fear memories can become labile when reactivated.
Figure 3: Intact memory if anisomycin infusions are delayed by 6 h.
Figure 4: Fourteen days after training, anisomycin infusions after reactivation of the memory still produce amnesia.
Figure 5: Amnesia following anisomycin is not due to nonspecific effects.

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Acknowledgements

This research was supported in part by NIMH grants to J.E.L. and a HFSF grant to K.N. The work was also supported by a grant from the W. M. Keck Foundation to N.Y.U. The authors thank A. Schoute for technical assistance.

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Correspondence to Karim Nader.

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Nader, K., Schafe, G. & Le Doux, J. Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406, 722–726 (2000). https://doi.org/10.1038/35021052

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