Hippocampal formation: shedding light on the influence of sex and stress on the brain

Abstract

The hippocampus is a malleable brain region that responds to external agents such as hormones and stressors. Investigations that began in our laboratories with the Golgi technique and an appreciation of hippocampal neuroanatomy at the light and electron microscopic levels have led us down a path that has uncovered unexpected structural plasticity in the adult brain along with unanticipated cellular and molecular mechanisms of this plasticity and of hormone mediation of these effects. This chapter reviews the history of discoveries in our two laboratories involving the actions of estradiol and stress hormones on neuronal structure and function and then discusses the insight to hormone-brain interactions that this has engendered. These discoveries have led us to a new view of brain structural plasticity and the role and mechanism of steroid hormone action involving both genomic and non-genomic pathways. This new view is consistent with the predictions of Cajal in his book "The Structure of Ammon's horn", 1892.

Figure 1

Camera lucida drawings of Golgi impregnated apical dendrites from CA1 pyramidal cells of animals in the proestrus (A) or estrus (B) phase of the estrous cycle. The arrows indicate some of the dendritic spines. Note the greater density of dendritic spines in A compared to B. Scale bar, 10 μm for both A and B. Reprinted from (Woolley et al., 1990) by permission.

Figure 2

Camera lucida drawings of CA3c pyramidal cells from the brains of sham-injected (A) and corticosterone-injected (B) animals. For these cells, numbers of dendritic branch points are: (A) 15 apical, and 10 basal; (B) 9 apical, and 9 basal. Dendritic length values for these cells are: (A) 1636.9 μm apical, and 1164.7 μm basal; (B) 1136.3 μm apical, and 1285.0 μm basal. Note the decrease in both the number of dendritic branch points and dendritic length in the apical tree of (B) compared to (A) while the basal tree shows no change in these parameters. Scale bar = 50 μm for A and B. Reprinted from (Woolley et al., 1990).

Figure 3

Camera lucida drawings of representative Golgi-impregnated dentate gyrus granule cells from brains of sham operated (A, B, C), adrenalectomized (I, E, F) and adrenalectomized plus corticosterone (G, H, I) animals. There is a decrease in dendritic branch points in all three cell types [granule cells located in the genu (A, D, G), granule cells with single primary dendrites (B, E, H) and granule cells with multiple primary dendrites (C, F, I) with adrenalectomy compared with sham operation and adrenalectomy plus corticosterone. From (Gould et al., 1990d) by permission.

Figure 4

ERα-, ERβ-, and AR- immunoreactivities have overlapping, yet distinct, distributions in the CA1 region of the rat hippocampus. A. ERα-immunoreactive nuclei (arrows) are found primarily in the border of strata radiatum (SR) and lacunosum-moleculare (SLM). B. Extranuclear ERβ-immunoreactivity is evident in pyramidal cell perikarya and their apical dendrites in SR. A few, scattered ERβ-labeled interneuron perikarya also are found. C. AR-immunoreactivity is primarily observed in pyramidal cell nuclei and in a few scattered glial processes (arrowheads). SO, stratum oriens; SP, stratum pyramidale. Bars, 500 μm

Figure 5

In the rat hippocampus, extranuclear ERα-is found postsynaptically in dendritic spines and presynaptically in terminals, some of which are cholinergic. A. ERα-immunoreactivity (arrowhead) is found in a dendritic spine emanating from a dendritic shaft. The spine is contacted (curved arrow) by an unlabeled terminal. B. A terminal with ERα-immunoreactivity (arrowhead) also contains silver intensified immunogold (black particles) labeling the cholinergic marker, vesicular acetylcholine transporter (VAChT). A, B, CA1 Stratum radiatum. Bars, 500 nm.

Figure 6

Extranuclear ERβ-immunoreactivity is detected in newly born cells in the rat dentate gyrus. A. A cell with silver intensified immunogold (black particles) for the new cell marker, doublecortin (DCX), also contains immunoreactivity for ERβ (arrowhead). B. Enlargement of the boxed region shows that the ERβ-immunoreactivity (arrowhead) is associated with a mitochondrion (m). Bars, 500 nm.

Figure 7

In the hippocampus, AR is found at nuclear sites in CA1 pryamidal cells and in extranuclear sites in dendritic spinces and glial cells. A. AR-immunoreactivity (arrowheads) is found in the nucleus of a pyramidal cell perikaryon. B. AR-immunoreactivity (arrowhead) is in a dendritic spine emanating from a dendritic shaft (D). The labeled spine is contacted by an unlabeled terminal (uT). C. AR immunoreactivity is found in two glial profiles (AR-g) that form a gap junction (arrow). The glial profiles abut the basement membrane (bm) of a blood vessel endothelial cell. A, B, CA1 Stratum radiatum. Bars, 500 nm.

Figure 8

Schematic diagram depicting the cellular and subcellular localization of ERs, PRs and ARs in the hippocampal CA1 region. Pyramidal cells contain nuclear labeling for AR (dark green) and a subset of GABAergic interneurons contains nuclear ERαs (dark pink). Pyramidal cells and some GABAergic interneurons contain cytosolic and plasma membrane-associated ERβs (blue). Dendritic spines, many belonging to pyramidal cells, contain ERαs, ERβs, ARs and PRs (purple). ERαs, ERβs, ARs and PRs are found in axons and axon terminals. Some ERα-containing terminals are cholinergic (acetylcholine; orange); some ERβ-containing terminals resemble monoaminergic terminals. Astrocytes (stars), mostly in the molecular layer, also contain ERαs, ERβs, ARs and PRs. (Summarized from Milner et al., 2001; 2005; Tabori et al., 2005; Towart et al., 2003; Waters et al., 2005).