Estradiol Regulates PSA-NCAM Expression and Connectivity of O-LM Interneurons in The Hippocampus of Adult Female Mice.

The estrous cycle is caused by the changing concentration of ovarian hormones, particularly 17β-Estradiol, a hormone whose effect on excitatory circuits has been extensively reported. However, fewer studies have tried to elucidate how this cycle, or this hormone, affects the plasticity of inhibitory networks and the structure of interneurons. Among these cells, somatostatin expressing O-LM neurons of the hippocampus have a role in the modulation of theta oscillations, and they receive direct input from the entorhinal cortex, which place them in the center of hippocampal function. In this study, we report that the expression of PSA-NCAM in the hippocampus, a molecule involved in the plasticity of somatostatin expressing interneurons in the adult brain, fluctuated through the different stages of the estrous cycle. Likewise, these stages and the expression of PSA-NCAM affected the density of dendritic spines of O-LM cells. We also describe that 17β-Estradiol replacement of adult ovariectomized female mice caused an increase of the perisomatic inhibitory puncta on O-LM interneurons, as well as an increase in their axonal bouton density. Interestingly, this treatment also induced a decrease in their dendritic spine density, specifically in O-LM interneurons lacking PSA-NCAM expression. Finally, using an ex vivo real-time assay with entorhino-hippocampal organotypic cultures we show that this hormone decreased the dynamics in spinogenesis, altogether highlighting the modulatory effect that 17β-Estradiol has on inhibitory circuits.