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Inactive but awake behaviour as indicating a depression-like state in mice: Aetiological factors and association with adult hippocampal neurogenesis

Lookup NU author(s): Ruth Davy, Rebecca-Leigh Railton, Dr Tom SmuldersORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

In laboratory mice, ‘inactive but awake’ (IBA) home-cage behaviour involves animals being spontaneously motionless with eyes open, not interacting with their surroundings. Conventional (barren) housing typically triggers IBA more than comparatively enriched environments. Compellingly greater IBA is associated with some depression-like features in mice and we further explored this through three aims. First, we aimed to replicate previous results highlighting environmental and genetic (using two strains of mice: DBA/2J and C57BL/6J) aetiological contributors to IBA. Second, we explored whether the performance of IBA varied as the level of enrichment was either increased or reduced. Third, we opportunistically investigated whether elevated IBA predicted lower density of immature neurons in the dorsal (dDG) or ventral dentate gyrus (vDG) of the hippocampus. As expected, mice housed in conventional cages displayed more IBA than those in comparatively enriched cages and even more so in DBA/2J mice. As predicted, enrichment loss generally increased IBA while enrichment gain decreased IBA. Unsurprisingly, immature neuron density was lower in conventional compared with enriched cages, although only for vDG. Elevated IBA predicted reduced immature neuron density in the dDG, and this effect tended to be stronger for C57BL/6Js. We discuss the result implications, study limitations and future research directions.

Publication metadata

Author(s): Trevarthen AC, Davy R, Finnegan EM, Railton R-L, Paul ES, Mendl MT, Smulders TV, Fureix C

Publication type: Article

Publication status: Published

Journal: Royal Society Open Science

Year: 2025

Volume: 12

Issue: 10

Online publication date: 15/10/2025

Acceptance date: 09/09/2025

Date deposited: 10/09/2026

ISSN (electronic): 2054-5703

Publisher: Royal Society Publishing

URL: https://doi.org/10.1098/rsos.251069

DOI: 10.1098/rsos.251069

Data Access Statement: All data and R script files used for statistical analyses and figure generation can be accessed in the Dryad repository (https://doi.org/10.5061/dryad.8cz8w9h59)

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