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

R Soc Open Sci. 2025 Oct 15;12(10):251069. doi: 10.1098/rsos.251069. eCollection 2025 Oct.

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.

PMID:41098813 | PMC:PMC12520784 | DOI:10.1098/rsos.251069