Molecular signature of rapid estrogen regulation of synaptic connectivity and cognition

There is now a growing appreciation that estrogens are capable of rapidly activating a number of signaling cascades within the central nervous system. In addition, there are an increasing number of studies reporting that 17β-estradiol, the major biologically active estrogen, can modulate cognition within a rapid time frame. Here we review recent studies that have begun to uncover the molecular and cellular framework which contributes to estrogens ability to rapidly modulate cognition. We first describe the mechanisms by which estrogen receptors (ERs) can couple to intracellular signaling cascades, either directly, or via the transactivation of other receptors. Subsequently, we review the evidence that estrogen can rapidly modulate both neuronal function and structure in the hippocampus and the cortex. Finally, we will discuss how estrogens may influence cognitive function through the modulation of neuronal structure, and the implications this may have on the treatment of a range of brain disorders.