Complementary stable and dynamic prelimbic ensembles encode learned threat value underlying generalization and discrimination.

Overview

Authors: Marc E Normandin¹, Pedro M Ogallar¹, Matthew R Lopez¹, Manuel M Ramos-Alvarez², Isabel A Muzzio¹

ORCID iDs: Marc E Normandin, Pedro M Ogallar, Isabel A Muzzio

Department of Psychological and Brain Sciences, University of Iowa Iowa City United States
Psychology Department, University of Jaén, Campus Las Lagunillas Jaén Spain

Institutions: University of Iowa (United States); Universidad de Jaén (Spain)

Journal: eLife, volume 15, article RP111177

Dates: published online 21 October 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.7554/elife.111177 · PMID 42904408 · PMCID PMC13686620 · OpenAlex W7161233182

Open access: gold, a free copy (OpenAlex)

Status: data only (how the code is found and verified)

Categories: mouse (organism)

Methods: Connectivity, Statistics, Machine learning, Preprocessing, fMRI & imaging, Single-unit activity, calcium imaging, Smoothing, state filtering, decompositions

Keywords: discrimination, dynamic ensembles, generalization, memory, sound processing, threat, Mouse

MeSH: Fear*, Generalization, Psychological*, Learning*, Neurons*, Prefrontal Cortex*, Animals, Male, Mice, Mice, Inbred C57BL (* major topic)

Journal subjects: Neuroscience

Topic: Memory and Neural Mechanisms (Cognitive Neuroscience, Neuroscience), according to OpenAlex

Funding: National Science Foundation (2303305); National Institute of Mental Health and Neurosciences (MH123260-01)

Citations: not cited yet (Europe PMC); 52 references in the paper

Research resources: AAV1-CaMKIIα-GCaMP6f-WPRE-SV40 RRID:Addgene_100834, C57BL/6 J RRID:IMSR_JAX_000664, FreezeFrame 5 RRID:SCR_014429, nVoke 2.0 miniscope system RRID:SCR_023028

Abstract

Adaptive behavior requires assigning emotional value to sensory cues and generalizing to similar stimuli. The prelimbic cortex (PL) is critical for threat expression and discrimination, yet its neuronal ensembles undergo substantial turnover over time. How stable population codes emerge despite this reorganization remains unknown. Using longitudinal calcium imaging in freely moving mice, we tracked PL activity for 30 days during auditory discriminative fear learning and retrieval. Despite substantial ensemble turnover, stable graded representations persisted in PL populations. A generalized linear model showed that the tone threat value explained graded activity better than freezing, indicating that PL primarily encodes stimulus significance. Population similarity across stimulus presentations was highest for shock-associated and highly generalized tones, suggesting a stable population code underlying threat generalization. Stable neurons preserved graded gradients across sessions, whereas learning modulated the rate of dynamic frequency-selective neurons. Together, these populations enabled stable threat-value coding despite ongoing ensemble reorganization.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data and to no code of its authors: see the Data section.

Tracing map

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Data

Datasets cited

doi:10.17632/9yyn63g346.3, at the source; found in the resources table
doi:10.17632/9yyn63g346.4, at the source; found in “Data availability”

Data availability

Datasets available at: https://doi.org/10.17632/9yyn63g346.4.

The following dataset was generated:

NormandinM OgallarP LopezM MuzzioI 2026normandin_et_al_mPFC_2026Mendeley Data10.17632/9yyn63g346.4

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 24 October 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 5 authors, 7 keywords, 9 MeSH terms, 2 funders, 52 references, 4 RRIDs.

Cite

This paper

Normandin, M. E., Ogallar, P. M., Lopez, M. R., Ramos-Alvarez, M. M., & Muzzio, I. A. (2026). Complementary stable and dynamic prelimbic ensembles encode learned threat value underlying generalization and discrimination. eLife, 15, RP111177. https://doi.org/10.7554/elife.111177

BibTeX

@article{normandin2026complementary, author = {Normandin, Marc E and Ogallar, Pedro M and Lopez, Matthew R and Ramos-Alvarez, Manuel M and Muzzio, Isabel A}, title = {{Complementary stable and dynamic prelimbic ensembles encode learned threat value underlying generalization and discrimination}}, journal = {eLife}, year = {2026}, month = oct, volume = {15}, pages = {RP111177}, publisher = {eLife Sciences Publications, Ltd}, issn = {2050-084X}, doi = {10.7554/elife.111177}, url = {https://doi.org/10.7554/elife.111177}, pmid = {42904408}, pmcid = {PMC13686620} }

RIS

TY - JOUR AU - Normandin, Marc E AU - Ogallar, Pedro M AU - Lopez, Matthew R AU - Ramos-Alvarez, Manuel M AU - Muzzio, Isabel A TI - Complementary stable and dynamic prelimbic ensembles encode learned threat value underlying generalization and discrimination T2 - eLife J2 - eLife PY - 2026 DA - 2026/10/21 VL - 15 SP - RP111177 SN - 2050-084X PB - eLife Sciences Publications, Ltd DO - 10.7554/elife.111177 UR - https://doi.org/10.7554/elife.111177 LA - en ER -

CSL-JSON

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