Cell birthdate effects on cell layering and function in the mouse dentate gyrus

This work explores unique features of early developmental neurogenesis in the dentate gyrus of the rodent hippocampus. It characterizes an outside-in layering of early- to late-born neurons in the dentate granule cell layer. It demonstrates that cells dividing during embryonic and postnatal life continue to divide infrequently through adult life. In fact, these early-dividing cells constitute most of the adult dividing population. Finally, it describes the ability of the postnatal brain to recover from an insult to neurogenesis (gancyclovir administered postnatally to Nestin-thymidine kinase transgenic animals). Mice with approximately 50% decreased dentate proliferation during postnatal days 5-9 sustain permanent anatomic deficits: both total granule cell number and adult neurogenesis are still decreased by about half at 13 weeks of age. Further, males only show corresponding behavior deficits in memory retention tasks. These findings contribute to the understanding of the origin and function of the adult dentate gyrus. They underscore that there are unique features of the postnatal brain that set the stage for lifetime learning and neurogenic ability. They also suggest future research into early clinical interventions to restore normal neurogenesis after experiences that may interfere with neurogenesis early in life.