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PreprintCC BYbioRxiv

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

  • C. McKenzie
  • A. I. Ramsaran
  • M. Saderi
  • S. Haar
  • S. A. Josselyn
  • P. W. Frankland1
  1. 1Hospital for Sick Children
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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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Cite

BibTeXRIS
BibTeX
@misc{mckenzie2026delayed,
  title = {{Delayed maturation of hippocampal trisynaptic circuitry underlies the protracted development of episodic-like memory}},
  author = {C. McKenzie and A. I. Ramsaran and M. Saderi and S. Haar and S. A. Josselyn and P. W. Frankland},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.14.759228},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.14.759228v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Delayed maturation of hippocampal trisynaptic circuitry underlies the protracted development of episodic-like memory
AU  - C. McKenzie
AU  - A. I. Ramsaran
AU  - M. Saderi
AU  - S. Haar
AU  - S. A. Josselyn
AU  - P. W. Frankland
PY  - 2026
DA  - 2026/10/14
PB  - bioRxiv
DO  - 10.64898/2026.10.14.759228
UR  - https://www.biorxiv.org/content/10.64898/2026.10.14.759228v1
AB  - 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.
ER  -