Fig. 1

A proposed model of the hippocampal microcircuit underlying the effects of increased serotonin on the dentate gyrus. First, chronic SSRI administration increases 5-HT levels, which results in activation of 5-HTRs on dentate gyrus granule cells. Activation of 5HT-_1ARs on mature granular cells ultimately results in release of downstream growth factors such as BDNF, VEGF, and others, which bind to receptors on neural precursor cells (NPCs) in the subgranular zone. NPCs then proliferate and differentiate into young adult born granule cells (abGCs), which will begin to migrate, mature, and finally integrate into the granule cell layer. However, the young abGCs have distinct plasticity properties from the mature dentate gyrus granule cells and activate local GABAergic interneurons to evoke strong inhibitory input to the mature granule cells