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bioRxiv · 10.64898/2026.10.14.759228

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

McKenzie, C.·Ramsaran, A. I.·Saderi, M.·Haar, S.·Josselyn, S. A.·Frankland, P. W.
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Abstract

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.

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McKenzie, C., Ramsaran, A. I., Saderi, M., Haar, S., Josselyn, S. A., Frankland, P. W.. 2026-10-16. Delayed maturation of hippocampal trisynaptic circuitry underlies the protracted development of episodic-like memory. https://doi.org/10.64898/2026.10.14.759228

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