It is well known that antidepressants both improve mood and increase the rate at which the dentate gyrus (DG) generates new neurons. In addition to the implications of neurogenesis for mood regulation, the production and survival of granule cells has also been implicated in learning and memory. Despite this evidence, the results of studies on the effect of antidepressants on memory have been mixed. A critical piece of data that may be missing from previous studies, however, is insight into (a) the location that newborn neurons migrate to following fluoxetine administration and (b) their ability to express normal patterns of activity-related genes. Here we demonstrate a finding that may resolve the discrepancy in the effects fluoxetine-induced neurogenesis on mood and memory: after 5 weeks delay, the net additional neurons generated in animals given the antidepressant fluoxetine during treatment are functionally normal, but preferentially accumulate (due to changes in migration and/or survival) in an area of the DG that is not recruited by spatial memory tasks.Highlights
▸ Adult hippocampal neurogenesis is consistently linked to both mood and memory. ▸ Fluoxetine's effect on memory is disputed, despite up-regulating neurogenesis. ▸ Knowing the location and function of newborn neurons may resolve this discrepancy. ▸ Fluoxetine-induced neurons express activity-related genes normally. ▸ Fluoxetine-induced neurons accumulate largely in areas not engaged by memory tasks.