Mechanisms of Critical Period in the Hippocampus Underlie Object Location Learning and Memory in Infant Rats

Learn Mem. 2018 Mar 15;25(4):176-182. doi: 10.1101/lm.046946.117. Print 2018 Apr.

Abstract

Episodic memories in early childhood are rapidly forgotten, a phenomenon that is associated with "infantile amnesia," the inability of adults to remember early-life experiences. We recently showed that early aversive contextual memory in infant rats, which is in fact rapidly forgotten, is actually not lost, as reminders presented later in life reinstate a long-lasting and context-specific memory. We also showed that the formation of this infantile memory recruits in the hippocampus mechanisms typical of developmental critical periods. Here, we tested whether similar mechanisms apply to a nonaversive, hippocampal type of learning. We report that novel object location (nOL) learned at postnatal day 17 (PN17) undergoes the typical rapid forgetting of infantile learning. However, a later reminder reinstates memory expression. Furthermore, as for aversive experiences, nOL learning at PN17 engages critical period mechanisms in the dorsal hippocampus: it induces a switch in the GluN2A/2B-NMDA receptor ratio, and brain-derived neurotrophic factor injected bilaterally into the dorsal hippocampus immediately after training results in long-lasting memory expression. We conclude that in infancy the hippocampus plays a necessary role in processing episodic and contextual memories, including nonaversive ones, and matures through a developmental critical period.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / administration & dosage
  • Brain-Derived Neurotrophic Factor / physiology
  • Critical Period, Psychological*
  • Female
  • Hippocampus / physiology*
  • Memory, Episodic*
  • Mental Recall / physiology
  • Rats, Long-Evans
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Spatial Learning / physiology*

Substances

  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • NR2B NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • N-methyl D-aspartate receptor subtype 2A