FIGURE 6.

Schematic diagrams illustrating the neuronal and spine morphology of monkey area 46 in response to aging, surgical menopause (ovariectomy), and hormonal manipulations and how these relate to working memory performance. Young ovariectomized monkeys treated with cyclic estradiol (E) or vehicle and aged ovariectomized monkeys treated with cyclic estradiol perform equally well on the delayed response test of working memory. Compared with young treated with cyclic E, the young receiving vehicle have lower spine density, but longer dendritic length; consequently, these two young groups have comparable numbers of spines per neuron. Aging results in decreased spine density, a selective loss of small thin spines, and a relative increase in mushroom spines. Aging combined with loss of cyclic E results in a further loss of thin spines such that these monkeys only have one-third the density of thin spines compared with the young cyclic E-treated subjects. Treatment regimens that included continuous E alone (Cont E), continuous E with cyclic or continuous progesterone (Cont E +P), or cyclic E with cyclic P (Cyc E +P) resulted in spine densities and morphologies that were comparable to vehicle treatment in aged ovariectomized monkeys. None of these treatments in aged ovariectomized monkeys restored working memory. Diagrams were drawn based on findings from Hao et al. (67) and Ohm et al. (159) and updated from Hara and Morrison (68). Only apical dendrites are drawn for simplicity, but similar changes occur in basal dendrites and throughout distal higher order dendrites.