Dentate gyrus neurons that are born at the peak of development, but not before or after, die in adulthood.

Introduction: In the dentate gyrus of the rodent hippocampus, neurogenesis begins prenatally and continues to the end of life. Adult-born neurons often die in the first few weeks after mitosis, but those that survive to 1 month persist indefinitely. In contrast, neurons born at the peak of development are initially stable but can die later in adulthood. Physiological and pathological changes in the hippocampus may therefore result from both the addition of new neurons and the loss of older neurons. The extent of neuronal loss remains unclear since no studies have examined whether neurons born at other stages of development also undergo delayed cell death.

Methods: We used BrdU to label dentate granule cells that were born in male rats on embryonic day 19 (E19; before the developmental peak), postnatal day 6 (P6; peak), and P21 (after the peak). We quantified BrdU neurons in separate groups of rats at 2 and 6 months post-BrdU injection to estimate cell death in young adulthood.

Results: Consistent with previous work, there was a 15% loss of P6-born neurons between 2 and 6 months of age. In contrast, E19- or P21-born neurons were stable throughout young adulthood.

Discussion: Delayed death of P6-born neurons suggests these cells may play a unique role in hippocampal plasticity adulthood, for example, by contributing to the turnover of hippocampal memory. Their loss may also play a role in disorders that are characterized by hippocampal atrophy.