Kempermann, GerdRünker, Annette2026-09-282026-09-2820242026-09-28https://opara.zih.tu-dresden.de/handle/123456789/2934https://doi.org/10.25532/OPARA-1569Genetically identical mice housed in the same enriched environment (ENR) develop divergent behavioural trajectories associated with differences in adult hippocampal neurogenesis and brain-wide connectivity. We asked whether such inter-individual differences are also reflected in the hippocampal transcriptome—not only as shifts in mean expression, but as effects on within-group variability. Analysing bulk hippocampal RNA-seq from isogenic standard- (STD) and ENR-housed mice, we identified highly variable genes (HVGs) that segregated into common, STD-specific and ENR-specific subsets. ENR did not uniformly increase transcriptional variability: it reduced highest variability in neuron-projection and synapse genes, while maintaining or increasing it in genes linked to extracellular matrix organization and oxidative phosphorylation. Mapped onto a WGCNA-derived ENR co-expression reference, HVGs were unevenly distributed across modules and concentrated at module hubs. Hub architecture and the position of non-hub HVGs differed between modules, corresponding to distinct functional programs: synaptic and chromatin-associated in two, RNA-processing and splicing in a third. Synaptic enrichment in STD-specific HVGs, extracellular-matrix enrichment in common HVGs and module-level localisation were stable across selection thresholds (5–20%). Hippocampal transcriptional variability is thus non-random, functionally coherent, embedded in co-expression architecture and shaped by environmental experience—suggesting it is an undervalued activity-dependent variable in the regulation of brain plasticity.Attribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/2::21