A sensitive period for the development of episodic-like memory in mice

Abstract

Episodic-like memory is a later-developing cognitive function supported by the hippocampus. In mice, the formation of extracellular perineuronal nets in subfield cornu ammonis (CA) 1 of the dorsal hippocampus controls the emergence of episodic-like memory during the fourth post-natal week. Whether the timing of episodic-like memory onset is hard-wired, or flexibly set by early-life experiences during a critical or sensitive period for hippocampal maturation, is unknown. Here, we show that the trajectories for episodic-like memory development vary for mice given different sets of experiences spanning the second and third post-natal weeks. Specifically, episodic-like memory precision developed later in mice that experienced early-life adversity, while it developed earlier in mice that experienced early-life enrichment. Moreover, we demonstrate that early-life experiences set the timing of episodic-like memory development by modulating the pace of perineuronal net formation in dorsal CA1, which is dependent on the brain-derived neurotrophic factor (BDNF)-tropomysin receptor kinase B (TrkB) signaling pathway. These results indicate that the hippocampus undergoes a sensitive period during which early-life experiences determine the timing for episodic-like memory development.

Keywords: critical period; development; early-life experience; engram; extracellular matrix; hippocampus; memory; perineuronal net; sensitive period.