The dentate gyrus grows throughout life despite turnover of developmentally-born neurons

Abstract

Adult-born hippocampal neurons are highly plastic but there remains uncertainty about the magnitude of neurogenesis and its long-term functional consequences. Theoretical predictions indicate that adult neurogenesis should lead to substantial growth of the dentate gyrus (DG) granule cell population. However, in practice, most studies find no changes in total cell number across adulthood. This discrepancy may partly be a sensitivity issue, where small sample sizes and the examination of older age windows (when neurogenesis is reduced) have prevented detection. However, neurogenic growth could also be masked by the turnover of developmentally-born DG neurons, which are known to die off in normal aging. To address the question of how neuronal birth and loss impacts DG population dynamics, here we quantified numbers of developmentally-born neurons, proliferating Ki67+ cells (as a proxy for adult-born neurons), and total DG neurons from 2-18 months of age in the rat. We estimate that over this timeframe 670,000 adult-born neurons are added (30% of the total population). Consistent with neurogenic growth, the total number of DG neurons increased across adulthood. However, net growth was only 385,000 cells, which is less than predicted by adult neurogenesis alone. Indeed, 20% of developmentally-born neurons were lost over the same interval, and so we propose that the difference is explained by neuronal turnover. Neuronal persistence and turnover may be relevant for theories of hippocampal long-term memory, as well as for understanding psychiatric conditions that are characterized by hippocampal plasticity and atrophy.