Dissociation between apoptosis, neurogenesis, and synaptic potentiation in the dentate gyrus of adrenalectomized rats

Removal of adrenal hormone corticosterone in rats aged 3-4 months results within 3 days in acceleration of apoptosis and proliferation of newborn cells in the dentate gyrus (DG). A critical question is whether such a shift in the maturity of dentate cells after adrenalectomy (ADX) affects synaptic plasticity. To address this question, male rats were adrenalectomized and synaptic potentiation was recorded in vitro in hippocampal slices, as well as in vivo, in response to high frequency stimulation of the perforant path, 3 days after ADX. At this time-point, cell loss was assessed and proliferation was examined. Based on two independent parameters, bromodeoxyuridine and Ki-67, we found that removal of the adrenal glands increases proliferation rate. This increase in proliferation was, in particular, evident in those animals that displayed substantial cell loss. The accelerated cell-turnover after ADX was accompanied by reduced synaptic potentiation, both when recorded in vitro and in vivo. Corticosterone replacement in vivo (in adrenalectomized animals), at levels that activate the mineralocorticoid receptor, prevented ADX-induced proliferation, apoptosis, and restored synaptic potentiation to control levels. Importantly, corticosterone applied to slices from adrenalectomized rats also normalized synaptic potentiation, despite increased proliferation. This suggests that changes in cell proliferation and apoptotic cell death in the DG are not necessarily key factors determining the efficacy of synaptic potentiation.