ROLE OF SEX HORMONES AND SEX CHROMOSOMES ON DORSAL CA1 NETWORK DYNAMICS AND SPATIAL CODING: IMPLICATIONS FOR SPATIAL LEARNING AND MEMORY

Despite increasing awareness of sex as a biological variable in neuroscience, most studies of hippocampal physiology still rely heavily on male mice. Sex-related differences in learning and memory have been described, potentially reflecting the influence of gonadal hormones and sex-chromosome complement. However, their differentiating roles in shaping hippocampal network dynamics and cells spatial coding remain poorly understood. The Four-Core-Genotype (FCG) mouse model provides a unique framework to dissociate chromosomal sex (XX vs XY) from gonadal sex, enabling mechanistic investigation of these factors at the circuit and cellular levels. Here, we examine how sex chromosomes and sex hormones influence dorsal CA1 hippocampal activity across behavioral states and spatial navigation contexts. We performed local field potential (LFP) recordings in head-fixed awake mice, including intact males, intact females monitored across the estrous cycle and ovariectomized females. We quantified electrophysiological dynamics across low-, mid-, and high-frequency oscillatory bands during running and quiet wakefulness to assess hormone- and chromosome-dependent modulation of physiological activity. Parallely, we imaged excitatory neurons of freely-moving mice during a linear-track task using calcium imaging with miniaturized microscopes, which allowed us to explore place-cell properties, spatial stability, and population coding together with behavioral tracking. Ongoing analyses aim to identify convergent and dissociable effects of sex hormones and sex chromosomes on CA1 oscillatory organization and place-cell dynamics. These findings are expected to advance mechanistic understanding of sex-related variability in hippocampal function and inform sex-aware models of cognition and disease.