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There are more DCX+ cells and LMTs in infant than in adult mice, indicating that there are more immature neurons (with immature synapses) in infant than in adult mice. There are more GFP+ cells in infant than in adult mice, indicating that the amount of neurogenesis is higher in infant mice than adults. Immunohistochemistry for DCX and Ki67 to compare the amount of neurogenesis in infant and adult mice.Ĭontext fear conditioning memory test to compare memory stability in infant and adult mice. Retroviral-GFP labeling to compare the amount of neurogenesis in infant and adult mice. The rate of neurogenesis decreases with age while memory stability increases with age. For all figures, error bars represent standard error of the mean (SEM). In all panels, cells/LMTs are expressed as number of cells/LMTs per 1000 μm 2. (J) Inverse relationship between neurogenesis and memory persistence predicts that increasing neurogenesis in adults will induce forgetting, whereas decreasing neurogenesis in infants will mitigate forgetting. Bottom row: High magnification of DG and CA3. (B) Top row: Infants had more DCX + cells in the DG and CA3 than adults. (Right) High magnification of CA3 region showing GFP + mossy fibers and LMTs. (Left) Low magnification of DG and CA3 regions. (A) GFP labeling of granule cells in the DG and CA3 1 month after retroviral infection shows that infant (P17) mice had higher levels of neurogenesis than adult (P60) mice. Age-dependent levels of hippocampal neurogenesis and memory stability are inversely related in mice. 1, B and F), consistent with a predicted reduction in synaptic rearrangements in the CA3 with age (fig. We observed a reduction in the number of immature (DCX +) large mossy fiber terminals (LMTs) in the CA3 region of adult mice ( Fig. Postnatally generated DG granule cells project a mossy fiber that reaches the CA3 region after ~2 weeks, contacting 11 to 15 pyramidal cells ( 5, 7, 23). S1) and immature ( doublecortin+ ) neurons ( Fig. From infancy to adulthood, there was also a decrease in the number of proliferating ( Ki67+) cells ( Fig. Four weeks after retroviral microinjections in infant (postnatal day 17 P17) and adult (P60) mice, we observed a pronounced age-dependent reduction in neurogenesis (i.e., reduction in the number of GFP + DG granule cells and their terminal processes in the CA3 region) ( Fig. We first characterized levels of hippocampal neurogenesis in infant and adult mice using a retrovirus expressing green fluorescent protein (GFP) to label neural progenitors and their progeny ( 11) and immunohistochemistry. Inverse Relationship Between Levels of Postnatal Neurogenesis and Memory Persistence

Here, we test whether postnatal hippocampal neurogenesis, in particular, modulates ontogenetic changes in memory persistence. Neurobiological accounts of infantile amnesia previously emphasized that continued brain maturation might interfere with consolidation and/or storage of infant memories, rendering them inaccessible at later time points ( 22). Consistent with this, infantile forgetting is observed across a wide range of species ( 20), including humans ( 21).

Therefore, this predicted remodeling-induced forgetting should be most pronounced during infancy, when hippocampal neurogenesis is high. As such remodeling necessarily alters the configuration of DG-CA3 circuits and likely rescales synaptic weights of preexisting connections, computational models predict that high levels of hippocampal neurogenesis will lead to forgetting of information already stored in those circuits ( 14– 16).Īlthough hippocampal neurogenesis persists throughout life, rates decline dramatically with age ( 17, 18). As new neurons integrate into the hippocampus, they compete with existing cells for inputs and outputs, establishing new synaptic connections that may coexist with, or even replace, older synaptic connections ( 5, 6, 13).

However, the continuous integration of new neurons may affect memories already stored in these circuits ( 12). Promoting the production of new neurons in adult mice facilitates the formation of new hippocampal memories ( 10, 11). These new neurons synaptically integrate into hippocampal circuits ( 4– 9) and provide potential substrates for new learning. In the hippocampus, new neurons continue to be generated in the subgranular zone of the dentate gyrus (DG) beyond development and into adulthood ( 2, 3). In both artificial systems and brain networks there is a trade-off between plasticity-the ability to incorporate new information-and stability-ensuring that the process of incorporating new information does not degrade information already stored in that network ( 1).