OSCR

Subregional activity in the dentate gyrus is amplified during elevated cognitive demands.

Overview

Authors: Charlotte CM Castillon1, Shintaro Otsuka1, John N Armstrong1, Anis Contractor1,2,3
ORCID iDs: Anis Contractor
  1. Department of Neuroscience, Feinberg School of Medicine, Northwestern University Chicago United States
  2. Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine Chicago United States
  3. Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University Chicago United States
Institutions: Northwestern University (United States); University of Chicago (United States)
Journal: eLife, volume 15, article RP109611
Dates: published online 14 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.7554/elife.109611 · PMID 42133696 · PMCID PMC13175573 · OpenAlex W7125382662
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism)
Methods: Statistics
Keywords: dentate gyrus, pattern separation, suprapyramidal blade, hippocampus, neural ensembles, spatial discrimination, Mouse
MeSH: Cognition*, Dentate Gyrus*, Neurons*, Animals, Male, Mice, Mice, Inbred C57BL (* major topic)
Journal subjects: Neuroscience
Topic: Neurogenesis and neuroplasticity mechanisms (Developmental Neuroscience, Neuroscience), according to OpenAlex
Funding: National Institutes of Health (R01NS115471, R01MH130428)
Citations: not cited yet (Europe PMC); 63 references in the paper
Research resources: Sheep Polyclonal anti-BrdU RRID:AB_10079353, Rabbit Polyclonal anti-RFP RRID:AB_10971665, Rabbit Monoclonal anti-HA tag RRID:AB_1549585, Rabbit Monoclonal anti-c-Fos RRID:AB_2247211, Donkey anti-rabbit Alexa Fluor 488/647 RRID:AB_2535792A-31573, Donkey anti-rabbit Alexa Fluor 488/647 RRID:AB_2536183, Donkey anti-sheep Alexa Fluor 488 RRID:AB_3750347

Abstract

Neural activity in the dentate gyrus (DG) supports the detection and discrimination of novelty, context, and patterns. Granule cell activation differs between the supra- and infrapyramidal blades across hippocampal-dependent tasks, yet how excitatory dynamics shape this blade-specific bias under varying cognitive demands remains unclear. Here, we combined an automated touchscreen pattern separation task in mice with temporally controlled tagging of active neurons to determine how increasing cognitive demand influences spatial activity patterns in the DG. As task difficulty increased, activation became progressively biased toward the suprapyramidal blade and was accompanied by structured distributions of active mature granule cells (mGCs) along both the radial and transverse axes. Selective inhibition of mGCs did not alter these spatial patterns, but profoundly impaired performance, as mice were no longer able to discriminate between closely spaced locations. In contrast, chemogenetic inhibition of adult-born dentate granule cells (abDGCs) beyond a critical maturation window impaired performance under high-demand conditions, increased overall mGC activity, and disrupted blade-specific organization even in animals that successfully completed the task. These findings demonstrate that high cognitive demand recruits spatially organized mGC activity and support a modulatory role for abDGCs in shaping dentate circuit dynamics.

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

Code

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Data

Datasets cited

Data availability

All data needed to evaluate the conclusions in the paper are available in the manuscript and/or the Supplementary Materials. Source data for this study are openly available in Zenodo at https://doi.org/10.5281/zenodo.19209813.

The following dataset was generated:

CastillonCCM OtsukaS ArmstrongJN ContractorA 2026Subregional activity in the dentate gyrus is amplified during elevated cognitive demandsZenodo10.5281/zenodo.19209813PMC1317557342133696

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

Versions

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 4 authors, 7 keywords, 7 MeSH terms, 1 funder, 62 references, 7 RRIDs.

Cite

This paper

Castillon, C. C., Otsuka, S., Armstrong, J. N., & Contractor, A. (2026). Subregional activity in the dentate gyrus is amplified during elevated cognitive demands. eLife, 15, RP109611. https://doi.org/10.7554/elife.109611

BibTeX

@article{castillon2026subregional,
author = {Castillon, Charlotte CM and Otsuka, Shintaro and Armstrong, John N and Contractor, Anis},
title = {{Subregional activity in the dentate gyrus is amplified during elevated cognitive demands}},
journal = {eLife},
year = {2026},
month = may,
volume = {15},
pages = {RP109611},
publisher = {eLife Sciences Publications, Ltd},
issn = {2050-084X},
doi = {10.7554/elife.109611},
url = {https://doi.org/10.7554/elife.109611},
pmid = {42133696},
pmcid = {PMC13175573}
}

RIS

TY - JOUR
AU - Castillon, Charlotte CM
AU - Otsuka, Shintaro
AU - Armstrong, John N
AU - Contractor, Anis
TI - Subregional activity in the dentate gyrus is amplified during elevated cognitive demands
T2 - eLife
J2 - Elife
PY - 2026
DA - 2026/05/14
VL - 15
SP - RP109611
SN - 2050-084X
PB - eLife Sciences Publications, Ltd
DO - 10.7554/elife.109611
UR - https://doi.org/10.7554/elife.109611
LA - en
ER -

CSL-JSON

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