All classes of antidepressants increase hippocampal cell proliferation and neurogenesis, which contributes, in part, to the behavioral actions of these treatments. Among antidepressant treatments, electroconvulsive seizure (ECS) is the most robust stimulator of hippocampal cell proliferation and the most efficacious treatment for depression, but the cellular mechanisms underlying the actions of ECS are unknown. To address this question, we investigated the effect of ECS on proliferation of neural stem-like and/or progenitor cells in the subgranular zone of rat dentate gyrus. We define the neural differentiation cascade from stem-like cells to early neural progenitors (also referred to as quiescent and amplifying neural progenitors, respectively) by coexpression of selective cellular and mitotic activity markers. We find that at an early mitotic phase ECS increases the proliferation of quiescent progenitors and then at a later phase increases the proliferation of amplifying progenitors. We further demonstrate that vascular endothelial growth factor (VEGF) signaling is necessary for ECS induction of quiescent neural progenitor cell proliferation and is sufficient to produce this effect. These findings demonstrate that ECS and subsequent induction of VEGF stimulates the proliferation of neural stem-like cells and neural progenitor cells, thereby accounting for the superior neurogenic actions of ECS compared with chemical antidepressants.depression ͉ neurogenesis ͉ antidepressant ͉ neurotrophic factor E lectroconvulsive seizure (ECS) therapy is considered the most effective treatment for depression, including patients who do not respond to chemical antidepressants (1-3). Recent studies demonstrate that all classes of antidepressants increase neurogenesis in the adult hippocampus, and this effect is thought to contribute, in part, to the actions of these treatments in rodent behavioral models (4-6). However, the cellular basis for the antidepressant induction of hippocampal neurogenesis has not been fully characterized. Previous studies have demonstrated that antidepressants, such as ECS and fluoxetine, increase cell proliferation within the subgranular zone (SGZ) and accelerate the maturation of immature neuron of the dentate gyrus in hippocampus but do not affect the differentiation of progenitor cells into neurons or glia (7-10). This indicates that one of the main targets for antidepressant-induced neurogenesis is to increase the mitotic activity of neural progenitor cells in the SGZ.Two major subclasses of proliferating cells have been characterized in the hippocampal SGZ based on the expression of phenotypic marker proteins. The first class is the putative stem cell that has a radial glia-like morphology, characterized by expression of glial fibrillary acidic protein (GFAP) and a relatively low rate of proliferative activity. This cell population is called the neural stem-like cell, type 1 cell, B cell, or quiescent neural progenitor (QNP) (11-13). The second class of cells is GFAP-negative, has a relatively hi...