Sex- and Region-Dependent Differences in Sharp Wave-Ripples Along the Long Axis of the Hippocampus

Sharp wave-ripples (SWRs) are transient hippocampal population events that coordinate neuronal ensemble activity and play a central role in memory consolidation and affective processing. Although SWRs exhibit marked functional specialization along the dorsoventral axis of the hippocampus, and several cellular mechanisms underlying SWRs are sex-sensitive, systematic comparisons of SWR properties between females and males are lacking. Here, we examined sex- and region-dependent differences in SWRs and associated multiunit activity (MUA) in acute hippocampal slices from adult female and male rats. Spontaneous SWRs were recorded from the CA1 stratum pyramidale of the dorsal and ventral hippocampus, and SWR occurrence rate, amplitude, ripple oscillation properties, and SWR-locked neuronal firing were quantified. Linear mixed-effects analysis revealed robust region-dependent differences across multiple SWR parameters. In contrast, sex effects were selective. SWR occurrence rate and amplitude did not differ significantly between females and males, whereas SWR-associated MUA showed a significant main effect of sex, with higher values in males. Ripple power was also influenced by sex, with higher values in females, together with a significant effect of region, suggesting differences in oscillatory structure. Baseline MUA did not differ between sexes, indicating that sex-related effects are specific to the SWR state. These findings suggest that sex does not substantially alter the generation of SWRs per se but influences neuronal recruitment and oscillatory properties during these events. Our results reveal previously underappreciated dimensions of hippocampal network organization and provide a descriptive framework for future studies investigating how sex-dependent circuit properties may shape hippocampal contributions to cognition and affective regulation. They further highlight the importance of incorporating sex as a fundamental biological variable in studies of hippocampal network dynamics.