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Infantile amnesia reflects a developmental critical period for hippocampal learning

Nature Neuroscience volume 19, pages 12251233 (2016) | Download Citation

  • An Erratum to this article was published on 27 June 2017

This article has been updated

Abstract

Episodic memories formed during the first postnatal period are rapidly forgotten, a phenomenon known as 'infantile amnesia'. In spite of this memory loss, early experiences influence adult behavior, raising the question of which mechanisms underlie infantile memories and amnesia. Here we show that in rats an experience learned during the infantile amnesia period is stored as a latent memory trace for a long time; indeed, a later reminder reinstates a robust, context-specific and long-lasting memory. The formation and storage of this latent memory requires the hippocampus, follows a sharp temporal boundary and occurs through mechanisms typical of developmental critical periods, including the expression switch of the NMDA receptor subunits from 2B to 2A, which is dependent on brain-derived neurotrophic factor (BDNF) and metabotropic glutamate receptor 5 (mGluR5). Activating BDNF or mGluR5 after training rescues the infantile amnesia. Thus, early episodic memories are not lost but remain stored long term. These data suggest that the hippocampus undergoes a developmental critical period to become functionally competent.

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Change history

  • 29 August 2016

    In the version of this article initially published, y-axis labels in Figures 3a,b, 4c, 5d and 6c report the “GluN2B/GluN2A ratio”; this should be changed to “GluN2A/GluN2B ratio.” The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank G. Pollonini for technical assistance. We thank P. Magistretti, F. Ansermet, K. Weiss, P. Balsam, X. Ye, F. Fiumara and G. Philips for discussions or comments on the manuscript. This work was supported by R01-MH074736 and an Agalma Foundation grant to C.M.A. and R01 NS072359 to R.D.B. A.T. was supported by a fellowship from Agalma Foundation. R.B. was supported by a fellowship from the Swiss National Science Foundation.

Author information

Affiliations

  1. Center for Neural Science, New York University, New York, New York, USA.

    • Alessio Travaglia
    • , Reto Bisaz
    •  & Cristina M Alberini
  2. Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Eric S Sweet
    •  & Robert D Blitzer
  3. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Eric S Sweet
  4. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Robert D Blitzer

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Contributions

C.M.A. led the design and development of the study and the writing of the manuscript; R.D.B, designed the electrophysiology study; A.T., R.B., E.S.S., R.D.B. and C.M.A. designed experiments and analyzed data; A.T. carried out behavioral experiments and the majority of molecular and pharmacological experiments; R.B. carried out behavioral experiments and contributed to molecular and pharmacological experiments; E.S.S. carried out electrophysiology experiments; and A.T., E.S.S., R.D.B. and C.M.A. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Cristina M Alberini.

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https://doi.org/10.1038/nn.4348

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