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Nat Neurosci. 2016 Sep;19(9):1225-33. doi: 10.1038/nn.4348. Epub 2016 Jul 18.

Infantile amnesia reflects a developmental critical period for hippocampal learning.

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Center for Neural Science, New York University, New York, New York, USA.
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.


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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