AGE- AND SEX-DEPENDENT LFP AND TRANSCRIPTOMIC SIGNATURES IN MOUSE CA1 HIPPOCAMPUS

Ageing and biological sex affect cognitive function and hippocampal network activity, but their interaction in CA1 circuit dynamics remains poorly understood. We combine acute electrophysiological recordings and single-cell transcriptomic profiling to investigate age- and sex-dependent alterations in mouse CA1. Acute local field potential (LFP) recordings were obtained from head-fixed young and aged male and female mice using 16-channel silicon probes targeting dorsal CA1. Signals were preprocessed with filtering, artefact rejection, and spectral decomposition to quantify oscillatory activity across theta, gamma, and ripple bands. Spike sorting was applied to extract single-unit activity, and coherence and cross-frequency coupling metrics were calculated. To provide a molecular perspective, publicly available 10x single-cell transcriptomic data were analysed from matched age and sex groups across major hippocampal excitatory and inhibitory populations (Sst, Pvalb, Lamp5, Lamp5Lhx6, CA1, dentate gyrus). Ageing produced pronounced transcriptional shifts: aged animals exhibited widespread upregulation of genes associated with mitochondrial stress, inflammatory activation, and synaptic downregulation, whereas young animals showed higher expression of activity-dependent and synaptic plasticity-related genes. Sexual dimorphism was extensive, with 28,204 sex-biased genes identified in different neuronal population. CA1 showed predominantly male-biased expression (~79%), while dentate gyrus and Lamp5 populations were strongly female-biased. Functional enrichment highlighted synaptic and neurodevelopmental pathways as the most sexually dimorphic, particularly in Lamp5 inhibitory neurons, whereas immune-related modules were enriched in female-biased populations. These analyses reveal substantial age- and sex-dependent molecular divergence in CA1 circuits. Integrating these data with electrophysiology will allow linking molecular ageing patterns to functional alterations in CA1 network activity.