Glucocorticoid and β-adrenergic regulation of hippocampal dendritic spines.

Glucocorticoid hormones are particularly potent with respect to enhancing memory formation. Notably, this occurs in close synergy with arousal (i.e., when norepinephrine levels are enhanced). In the present study, we examined whether glucocorticoid and norepinephrine hormones regulate the number of spines in hippocampal primary neurons. We report that brief administration of corticosterone or the β-adrenergic receptor agonist isoproterenol alone increases spine number. This effect becomes particularly prominent when corticosterone and isoproterenol are administered together. In parallel, corticosterone and isoproterenol alone increased the amplitude of miniature excitatory postsynaptic currents, an effect that is not amplified when both hormones are administered together. The effects of co-application of corticosterone and isoproterenol on spines could be prevented by blocking the glucocorticoid receptor antagonist RU486. Taken together, both corticosterone and β-adrenergic receptor activation increase spine number, and they exert additive effects on spine number for which activation of glucocorticoid receptors is permissive.