Our data support the hypothesis that estrogen enhances an increase in Arc, PSD-95, and SYP expression as well as synaptic plasticity via activation of ER_. These findings not only support previous studies showing that estrogen increased PSD-95 and SYP expression via ER_ activation in classical genomic pathway [18], but also demonstrate the translocation of cytosolic ER_ to the nucleus which in turn activates PSD-95 and SYP expression after prolong estrogen treatment.