Delayed maturation of hippocampal trisynaptic circuitry underlies the protracted development of episodic-like memory

The ability to form high-resolution episodic memories emerges relatively late in development, but the circuit mechanisms underlying this transition are unknown. CA1 receives entorhinal input through a direct monosynaptic pathway and an indirect trisynaptic pathway via the dentate gyrus and CA3. In mice, CA3[->]CA1 innervation matured later than MEC[->]CA1 innervation, with pronounced maturation between P20 and P24. Trisynaptic pathway maturation was necessary for high-resolution memory and was shaped by neuronal activity and early-life experience. Mechanistically, trisynaptic activity promoted perineuronal net assembly around downstream parvalbumin-expressing interneurons, facilitating their maturation and subsequent recruitment during learning to constrain CA1 encoding ensembles. Thus, activity-dependent maturation of trisynaptic circuitry provides a unified circuit and cellular account of a sensitive period for the emergence of episodic-like memory.