Quantitative analysis of ER alpha and GAD colocalization in the hippocampus of the adult female rat.

Despite the many effects of estrogen in the hippocampus, there has been little evidence that hippocampal principal cells express nuclear estrogen receptors. In the hippocampus, the alpha form of the nuclear estrogen receptor (ER alpha) has been localized to sparsely distributed cells with the morphological characteristics of inhibitory interneurons. Because inhibitory neurons may be involved in the effects of estrogen on hippocampal principal cells, quantitative description of ER alpha expression in gamma-aminobutyric acid (GABA)ergic (inhibitory) and non-GABAergic cells of the hippocampus is a key step in understanding the mechanism(s) of estrogen action on hippocampal circuitry. We used single and double-label immunohistochemistry for ER alpha and glutamic acid decarboxylase (GAD; a marker of GABAergic neurons) to determine the numbers and distributions of hippocampal GABAergic and non-GABAergic neurons that express ER alpha in the adult female rat. We found many more ER alpha-expressing cells in the hippocampus than any previous study and observed distinct dorsal vs. ventral differences in hippocampal ER alpha expression. In the dorsal hippocampus, most ER alpha-positive cells were also GAD positive; however, ER alpha was expressed in only a subset of GAD-positive cells. Double-labeled cells were concentrated at the border between str. radiatum and str. lacunosum-moleculare. In the ventral hippocampus, we found a very high number of ER alpha-positive cells, the majority of which were not immunoreactive for GAD and are likely to be pyramidal cells. These findings suggest that ER alpha can mediate the effects of estrogen primarily in GABAergic neurons in the dorsal hippocampus and in both GABAergic and non-GABAergic neurons in the ventral hippocampus. Copyright 2001 Wiley-Liss, Inc.