The “preschool” years of infancy and early childhood (up to ~age 4) represent a critical period of rapid learning stimulated by experience. However, humans cannot remember events from this time in their lives, a phenomenon called infantile amnesia. Why then do early experiences influence adult behavior, and what enables humans to form enduring memories after age 4? Using rats, which also show infantile amnesia, Travaglia et al. (see also Rudenko and Tsai) showed that a glutamate receptor subunit switch promotes the maturation of memory retrieval in the hippocampus and that infantile memories are not actually lost but are latent and can be recalled with contextual cues. In rats, memories formed through associative learning training during the period around postnatal day 17 (P17) quickly decay, whereas those formed at P24 endure. The contextual memory of foot shock training in P17 rats (here, associating a shock with entering a dark compartment) disappeared within 24 hours; however, exposing these rats weeks later to both the context and a reminder foot shock in close succession reinstated the memory, as evident by increased time before entering the dark box in future tests. Pharmacologically blocking neural activity in the dorsal hippocampus by injection of the GABAA agonist muscimol prevented the shocked-trained rats from reinstating this memory. When compared with the hippocampi from untrained rats or rats trained when older, hippocampi from rats shock-trained at P17 exhibited an increase in phosphorylation (activation) of the neurotrophin receptor tyrosine kinase TrkB and a switch in the composition ratio of NMDA-type glutamate receptors from GluN2B subunits to predominantly GluN2A subunits. Subsequent molecular and pharmacological experiments in vivo indicated that the neurotrophic factor BDNF and the metabotropic glutamate receptor mGluR5 were critical for the training-induced increase in phosphorylated TrkB or the GluN2B:GluN2A switch and the future memory reinstatement. The formation and storage of latent infantile (P17) associative memories required GluN2B, whereas the formation of enduring associative memories at P24 required GluN2A. Injecting BDNF or the metabotropic glutamate receptor agonist DHPG into the dorsal hippocampus of P17 rats after training induced enduring memory, effectively closing the infantile amnesia period. The findings describe a molecular mechanism underlying the maturation of memory processing in the hippocampus and why infantile experiences that are seemingly forgotten can contribute to behavior later in life.
A. Travaglia, R. Bisaz, E. S. Sweet, R. D. Blitzer, C. M. Alberini, Infantile amnesia reflects a developmental critical period for hippocampal learning. Nat. Neurosci. 19, 1225–1233 (2016). [PubMed]
A. Rudenko, L.-H. Tsai, The hippocampus grows up. Nat. Neurosci. 19, 1190–1191 (2016). [PubMed]