Effects of oestradiol on hippocampal circuitry

Oestradiol produces structural and functional changes in hippocampal circuitry of adult female rats. The density of both dendritic spines and axospinous synapses on hippocampal CA1 pyramidal cells is regulated by oestradiol. Additionally, oestradiol-induced differences in synaptic connectivity are paralleled by changes in NMDA receptor binding, immunoreactivity for NMDA receptors and sensitivity to NMDA receptor-mediated synaptic input. Curiously, while oestradiol effects are observed in CA1 pyramidal cells, most evidence indicates that these cells lack genomic oestradiol receptors. In contrast, at least some inhibitory neurons in CA1 do express oestradiol receptors. Others' in vitro studies suggest that oestradiol-induced increases in spine density require an initial decrease in inhibitory (GABAergic) drive onto pyramidal cells. We have used single and double label immunohistochemistry for c-Fos (as a measure of neuronal activation) and glutamic acid decarboxylase 65 (as a marker for inhibitory circuitry) to determine: (1) which hippocampal neuronal populations are activated by oestradiol and the time-course of this activation, as well as (2) whether oestradiol affects inhibitory circuitry in vivo as it does in vitro. Our findings are consistent with the suggestion that oestradiol increases dendritic spine density through a mechanism involving disinhibition of pyramidal cells.