Supramammillary area mediates subcortical estrogenic action on hippocampal synaptic plasticity

It is well established that systemically administered estrogen to ovariectomized rats positively affects the density of pyramidal cell spines in the hippocampal CA1 subfield and intact subcortical connections of the hippocampus are essential in this hormonal action. This study explored whether local estrogen administration into the supramammillary area influences the density of CA1 pyramidal cell spine synapses in ovariectomized rats. The first group of experiments using a combination of retrograde tracer technique and immunostaining for estrogen receptor-alpha demonstrated that a large population of supramammillary area estrogen receptor-alpha-containing neurons projects to the hippocampus. Animals belonging to the second experimental group were ovariectomized and received cannulae filled with 0.4% 17 beta-estradiol placed unilaterally into the supramammillary area. Control animals received a cholesterol-containing cannula into the supramammillary area or an estrogen-filled cannula implanted into the head of the caudate nucleus. One week later, rats were killed and CA1 pyramidal cell spine synapse density was determined using electron microscopic unbiased stereological procedures. Animals that received an estrogen-filled cannula into the supramammillary area exhibited a significantly higher (37%) density of CA1 pyramidal cell spine synapses than both other control groups. These observations indicate that the supramammillary area is involved in mediating synaptoplastic, estrogenic effects to the hippocampus.