Oestradiol-Induced Synapse Formation in the Female Hippocampus: Roles of Oestrogen Receptor Subtypes

During the oestrus cycle, varying spine synapse density correlates positively with varying local synthesis of oestradiol in the hippocampus. In this context, the roles of the oestrogen receptor (ER) subtypes ER and are not fully understood. In the present study, we used neonatal hippocampal slice cultures from female rats because these cultures synthesise oestradiol and express both receptor subtypes, and inhibition of oestradiol synthesis in these cultures results in spine synapse loss. Using electron microscopy, we tested the effects on spine synapse density in response to agonists of both ER and ER. Application of agonists to the cultures had no effect. After inhibition of oestradiol synthesis, however, agonists of ER induced spine synapse formation, whereas ER agonists led to a reduction in spine synapse density in the CA1 region of these cultures. Consistently, up-regulation of ER in the hippocampus of adult female aromatase-deficient mice is paralleled by hippocampus-specific spine synapse loss in this mutant. Finally, we found an increase in spine synapses in the adult female ER knockout mouse, but no effect in the adult female ER knockout mouse. Our data suggest antagonistic roles of ER and ER in spine synapse formation in the female hippocampus, which may contribute to oestrus cyclicity of spine synapse density in the hippocampus.