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 many of the 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 dorsal and ventral hippocampus, and SWR amplitude, frequency, ripple oscillation properties, and SWR-locked neuronal firing were quantified. In the dorsal hippocampus, females exhibited a significantly higher SWR occurrence rate than males, whereas SWR amplitude was similar between sexes. In contrast, SWR-locked MUA was significantly higher in males, despite their lower SWR frequency. In the ventral hippocampus, females and males showed comparable SWR amplitude and frequency; however, males again displayed enhanced SWR-locked MUA, accompanied by reduced ripple power. Baseline MUA did not differ between sexes in either hippocampal region, indicating that sex-related effects were specific to the SWR state. These findings demonstrate that SWRs are regulated in a sex- and region-dependent manner, with dissociable effects on event recurrence, oscillatory structure, and neuronal recruitment. We propose that sex-sensitive mechanisms, including GABAergic interneuron function, steroid hormone signaling, and intrinsic and synaptic excitability, differentially tune SWR initiation and pyramidal cell recruitment along the dorsoventral axis. Our results reveal previously unrecognized dimensions of hippocampal network organization providing a mechanistic framework for understanding how sex-dependent circuit properties may shape hippocampal contributions to cognition and affective regulation and highlight the importance of incorporating sex as a fundamental biological variable in studies of hippocampal network dynamics.