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 lit tle evidence that hippocampal principal cells express nuclear estrogen rece ptors. In the hippocampus, the a form of the nuclear estrogen receptor (ER alpha) has been localized to sparsely distributed cells with the morphologi cal 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 k ey step in understanding the mechanism(s) of estrogen action on hippocampal circuitry. We used single and double-label immunohistochemistry for ER alp ha and glutamic acid decarboxylase (GAD; a marker of GABAergic neurons) to determine the numbers and distributions of hippocampal. GABAergic and non-G ABAergic neurons that express ER alpha in the adult female rat. We found ma ny more ER alpha -expressing cells in the hippocampus than any previous stu dy and observed distinct dorsal vs. ventral differences in hippocampal ER a lpha expression. In the dorsal hippocampus, most ER alpha -positive cells w ere also GAD positive; however, ER alpha was expressed in only a subset of GAD-positive cells. Double-labeled cells were concentrated at the border be tween str. radiatum and str. lacunosum-moleculare. In the ventral hippocamp us, we found a very high number of ER alpha -positive cells, the majority o f which were not immunoreactive for GAD and are likely to be pyramidal cell s. These findings suggest that ER alpha can mediate the effects of estrogen primarily in GABAergic neurons in the dorsal hippocampus and in both GABAe rgic and non-GABAergic neurons in the ventral hippocampus. J. Comp. Neurol. 440:144-155, 2001. (C) 2001 Wiley-Liss, Inc.