Estrous cycle regulates activation of hippocampal Akt, LIM kinase, and neurotrophin receptors in C57BL/6 mice

Estradiol modulates dendritic spine morphology and synaptic protein expression in the rodent hippocampus, as well as hippocampal-dependent learning and memory. In the rat, these effects may be mediated through nongenomic steroid signaling such as estradiol activation of the Akt and LIM kinase (LIMK) pathways, in addition to genomic signaling involving estradiol upregulation of brain-derived neurotrophic factor expression (BDNF). Due to the many species differences between mice and rats, including differences in the hippocampal response to estradiol, it is unclear whether estradiol modulates these pathways in the mouse hippocampus. Therefore, we investigated whether endogenous fluctuations of gonadal steroids modulate hippocampal activation of the Akt, LIMK, and the BDNF receptor TrkB in conjunction with spatial memory in female C57BL/6 mice. We found that Akt, LIMK, and TrkB were activated throughout the dorsal hippocampal formation during the high-estradiol phase, proestrus. Cycle phase also modulated expression of the pre- and post-synaptic markers synaptophysin and post-synaptic density 95. However, cycle phase did not influence performance on an object placement test of spatial memory, although this task is known to be sensitive to the complete absence of ovarian hormones. The findings suggest that endogenous estradiol and progesterone produced by the ovaries modulate specific signaling pathways governing actin remodeling, cell excitability, and synapse formation.