Recovery of memory from infantile amnesia is developmentally constrained.

Episodic memories formed during infancy are rapidly forgotten, a phenomenon associated with infantile amnesia, the inability of adults to recall early-life memories. In both rats and mice, infantile memories, although not expressed, are actually stored long term in a latent form. These latent memories can be reinstated later in life by certain behavioral reminders or by artificial reactivations of neuronal ensembles activated at training. Whether the recovery of infantile memories is limited by developmental age, maternal presence, or contingency of stimuli presentation remains to be determined. Here, we show that the return of inhibitory avoidance memory in rats following a behavioral reactivation consisting of an exposure to the context (conditioned stimuli [CS]) and footshock (unconditioned stimuli [US]) given in a temporally unpaired fashion, is evident immediately after US and is limited by the developmental age at which the reactivations are presented; however, it is not influenced by maternal presence or the time interval between training and reactivation. We conclude that one limiting factor for infantile memory reinstatement is developmental age, suggesting that a brain maturation process is necessary to allow the recovery of a "lost" infantile memory.

Mechanisms of critical period in the hippocampus underlie object location learning and memory in infant rats.

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.

Hippocampal parvalbumin interneurons play a critical role in memory development.

Episodic memories formed in early childhood rapidly decay, but their latent traces remain stored long term. These memories require the dorsal hippocampus (dHPC) and seem to undergo a developmental critical period. It remains to be determined whether the maturation of parvalbumin interneurons (PVIs), a major mechanism of critical periods, contributes to memory development. Here, we show that episodic infantile learning significantly increases the levels of parvalbumin in the dHPC 48 h after training. Chemogenetic inhibition of PVIs before learning indicated that these neurons are required for infantile memory formation. A bilateral dHPC injection of the γ-aminobutyric acid type A receptor agonist diazepam after training elicited long-term memory expression in infant rats, although direct PVI chemogenetic activation had no effect. Finally, PVI activity was required for brain-derived neurotrophic factor (BDNF)-dependent maturation of memory competence, i.e., adult-like long-term memory expression. Thus, dHPC PVIs are critical for the formation of infantile memories and for memory development.