Unilateral Fimbria/Fornix Transection Prevents the Synaptoplastic Effect of Dehydroepiandrosterone in the Hippocampus of Female, but Not Male, Rats

Dehydroepiandrosterone (DHEA), the most abundant adrenal androgen in primates, is also synthesized from cholesterol in the brain. Like testosterone, DHEA induces spine synapse formation in the hippocampus. In female rats, this response is blocked by co-administration of an inhibitor of aromatase, the enzyme responsible for estrogen biosynthesis. In males, by contrast, the hippocampal synaptic response to DHEA is unaffected by treatment with an aromatase inhibitor. We hypothesized that this sex difference might reflect differential dependence of the hippocampal responses on subcortical afferents from the basal forebrain. To test this hypothesis, we examined the effects of unilateral fimbria/ fornix transection (FFX) on DHEA-induced synapse formation in the cornu ammonis 1 (CA1) hippocampal subfield of gonadectomized female and male rats. In ovariectomized females, CA1 spine synapse density after DHEA treatment was reduced by more than 60% ipsilateral to FFX. In males, however, unilateral FFX transection had no effect on spine synapse density after DHEA treatment. These results suggest that sex differences in the dependence on local estrogen biosynthesis of the CA1 synaptic response to androgen may at least in part be the result of sex differences in the relative contributions of afferents to the hippocampus from the basal forebrain.