Abstract
Functions of the hippocampus is dependent on brain-derived-neurosteroids. Because estrogen is synthesized locally in the hippocampus, as well as supplied from the ovary, its functions are attracting much attention. Hippocampal sex-steroids modulate memory-related synaptic plasticity not only slowly but also rapidly. Slow actions of estradiol (E2) occur via nuclear receptors (ERα), while rapid E2 actions occur via synapse-localized ERα. Elevation or decrease of the E2 concentration changes rapidly the density and morphology of spines. Kinase networks are involved downstream of ERα. The long-term depression is modulated rapidly by changes of E2 level. The E2 level is much higher than that in blood circulation. Hippocampus-derived sex-steroids play a major role in modulation of synaptic plasticity.