Inverse relationship between adult hippocampal cell proliferation and synaptic rewiring in the dentate gyrus

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Abstract
Adult neurogenesis is a key feature of the hippocampal dentate gyrus (DG). Neurogenesis is accompanied by synaptogenesis as new cells become integrated into the circuitry of the hippocampus. However, little is known to what extent the embedding of new neurons rewires the pre-existing network. Here we investigate synaptic rewiring in the DG of gerbils (Meriones unguiculatus) under different rates of adult cell proliferation caused by different rearing conditions as well as juvenile methamphetamine treatment. Surprisingly, we found that an increased cell proliferation reduced the amount of synaptic rewiring. To help explain this unexpected finding, we developed a novel model of dentate network formation incorporating neurogenesis and activity-dependent synapse formation and remodelling. In the model, we show that homeostasis of neuronal activity can account for the inverse relationship between cell proliferation and synaptic rewiring.