Early intrinsic excitability plasticity of neocortical engram neurons defines memory formation and precision

1. Nat Commun. 2025 Dec 5;17(1):291. doi: 10.1038/s41467-025-66975-3.

Early intrinsic excitability plasticity of neocortical engram neurons defines
memory formation and precision.

Hadzibegovic S(#)(1)(2), Zhu L(#)(1)(2), Ginger M(1)(2), Gueidão Costa
M(1)(2)(3), Alvarez Menendez P(1)(2), De Sa R(1)(2), Le Corf K(1)(2), Le Feuvre
Y(1)(2), Nicole O(2)(4), Bontempi B(5)(6), Frick A(7)(8).

Author information:
(1)INSERM U1215, Neurocentre Magendie, Bordeaux, France.
(2)University of Bordeaux, Bordeaux, France.
(3)University of the Basque Country, Leioa, Spain.
(4)CNRS, IINS, UMR 5297, Bordeaux, France.
(5)University of Bordeaux, Bordeaux, France. .
(6)CNRS, INCIA, UMR 5287, Bordeaux, France. .
(7)INSERM U1215, Neurocentre Magendie, Bordeaux, France.
.
(8)University of Bordeaux, Bordeaux, France. .
(#)Contributed equally

Neocortical memory engrams are thought to mature via strengthened
interconnectivity, yet synaptic plasticity alone cannot explain the dynamic
vividness of enduring memories. Neuronal intrinsic excitability (IE) plasticity
has been touted as an early priming mechanism that renders engram neurons
susceptible to ongoing plastic processes and later encoding events. Here, we
reveal that learning-induced IE plasticity of nascent anterior cingulate cortex
(ACC) engram neurons is a permissive mechanism for the formation and specificity
of remote memories. Using c-fos-dependent genetic/viral targeting in mice, we
found that contextual fear learning triggered a time-limited increase in ACC
engram IE during the early phase of memory formation. Remarkably,
chemogenetically hyperpolarizing these neurons within-but not outside-the IE
plasticity window strengthened consolidated memories, enhanced their
context-precision, and prevented interference-induced engram reallocation. Thus,
IE plasticity in nascent ACC engram neurons acts as an essential tagging
mechanism that determines the fate and dynamic content of remote memories.

© 2025. The Author(s).

DOI: 10.1038/s41467-025-66975-3
PMCID: PMC12783673
PMID: 41350518 [Indexed for MEDLINE]

Conflict of interest statement: Competing interests: The authors declare no
competing interests.

Auteurs Bordeaux Neurocampus