Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. Here we demonstrated the rapid effect of estradiol on the density of thorns of thorny excrescences, by imaging Lucifer Yellow-injected CA3 neurons in adult male rat hippocampal slices. The application of 1 nM estradiol induced rapid decrease in the density of thorns on pyramidal neurons within 2 h. The estradiol-mediated decrease in the density of thorns was blocked by CNQX (AMPA receptor antagonist) and PD98059 (MAP kinase inhibitor), but not by MK-801 (NMDA receptor antagonist). ER alpha agonist PPT induced the same suppressive effect as that induced by estradiol on the density of thorns, but ER beta agonist DPN did not affect the density of thorns. Note that a 1 nM estradiol treatment did not affect the density of spines in the stratum radiatum and stratum oriens. A search for synaptic ER alpha, was performed using purified RC-19 antibody. The localization of ER alpha (67 kDa) in the CA3 mossy fiber terminals and thorns was demonstrated using immunogold electron microscopy. These results imply that estradiol drives the signaling pathway including ER alpha, and MAP kinase. (c) 2005 Elsevier Inc. All rights reserved.