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The consolidation of new but not reactivated memory requires hippocampal C/EBPβ

Abstract

Long-term memory formation consists of multiple phases. A new memory is initially labile and sensitive to disruption by a variety of interfering events or agents. To become stable, this new memory undergoes a process known as consolidation, which, in the case of declarative memories, occurs within the medial temporal lobes and requires gene expression. When recalled, memories re-enter a new phase of vulnerability and seem to require a reconsolidation process in order to be maintained. Here we show that consolidation but not reconsolidation of inhibitory avoidance memory requires the expression of the transcription factor CCAAT enhancer binding protein β (C/EBPβ) in the hippocampus. Furthermore, in the same region, de novo protein synthesis is not essential for memory reconsolidation. C/EBPβ is an evolutionarily conserved genetic marker that has a selective role in the consolidation of new but not reactivated memories in the hippocampus.

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Figure 1: Biotinylated β-ODN distribution and relative concentrations after infusion (2 nmol/μl, 1 μl injected).
Figure 2: The induction of C/EBPβ after IA training is blocked by antisense β-ODN injection.
Figure 3: C/EBPβ antisense blocks long-term memory consolidation.
Figure 4: Hippocampal C/EBPβ antisense or anisomycin injections do not interfere with the consolidation of reactivated memory.

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Acknowledgements

This work was supported by the Whitehall Foundation (grant # F97-07). The authors thank J. McGaugh and B. Roozendaal for teaching the cannulae implantation technique, J. LeDoux, R. Bourtchouladze, G. Schafe and R. Burwell for reading the manuscript and for discussions, V. Poli for providing the rat C/EBPβ clone, and E. Sklar, A. Beauregard-Young and J. Harper for technical assistance. C.M.A. is on a leave of absence from Dipartimento Materno Infantile e Tecnologie Biomediche, University of Brescia, Italy. B.M. was a recipient of a HFSPO short-term fellowship.

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Correspondence to Cristina M. Alberini.

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Taubenfeld, S., Milekic, M., Monti, B. et al. The consolidation of new but not reactivated memory requires hippocampal C/EBPβ. Nat Neurosci 4, 813–818 (2001). https://doi.org/10.1038/90520

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