[Show abstract][Hide abstract] ABSTRACT: Author Summary
The birth of adult hippocampal neurons is associated with enhanced learning and memory performance. In particular, spatial learning increases the survival and the proliferation of newborn cells, but surprisingly, it also decreases their number. Here, we hypothesized that spatial learning also depends upon the death of newborn hippocampal neurons. We examined the effect of spatial learning in the water maze on cell birth and death in the rodent hippocampus. We then determined the influence of an inhibitor of cell death on memory abilities and learning-induced changes in cell death, cell proliferation, and cell survival. We show that learning increases the elimination of the youngest newborn cells during a specific developmental period. The cell-death inhibitor impairs memory abilities and blocks the learning-induced cell death, the survival-promoting effect of learning on older newly born neurons, and the subsequent learning-induced proliferation of neural precursors. These results show that spatial learning induces cell death in the hippocampus, a phenomenon that subserves learning and is necessary for both the survival of older newly born neurons and the proliferation of neural precursors. These findings suggest that during learning, neuronal networks are sculpted by a tightly regulated selection of newly born neurons and reveal a novel mechanism mediating learning and memory in the adult brain.