Sex-Specific Difference of Hippocampal Synaptic Plasticity in Response to Sex Neurosteroids

This study demonstrated that sex neurosteroids contribute to sex-specific hippocampal synaptic plasticity. It was found that testosterone and its metabolite dihydrotestosterone were crucial for hippocampal synaptic transmission in males, affecting the density of mushroom spines and spine synapses. In contrast, inhibition of testosterone conversion to estradiol predominantly impacted synaptic transmission in females. These sex-dependent differences were also observed in primary hippocampal cultures from perinatal animals, suggesting that sex-specific differentiation of hippocampal neurons in response to neurosteroids occurs up to birth and persists into adulthood. The findings indicated a developmental effect potentially induced by sex chromosomes or fetal testosterone secretion during a critical perinatal period.