Estrogen has also been shown to increase spine density and neurite outgrowth in vitro in hippocampal neuronal cultures [239,246]. Additionally, estrogen enhances long term potentiation (LTP) in the hippocampus, which is a postulated model for the synaptic changes that may underlie learning and memory [237–250]. Interestingly, induction of LTP in the CA1 region of the hippocampus has been shown to be enhanced on proestrus, which correlates with peak serum estrogen levels and spine density enhancement observed on proestrus [251,252]. It should be mentioned that despite more than a century of fascination with dendritic spines, little is known about their assumed role in memory storage and learning. However, there is growing evidence that dendritic spines are indeed involved in learning and memory [see 253–257, for review]. Several lines of evidence support this contention.