The presence of new neurons in the adult hippocampus indicates that this structure incorporates new neurons into its circuitry and uses them for some function related to learning and/or related thought processes. Their generation depends on a variety of factors ranging from age to aerobic exercise to sexual behavior to alcohol consumption. However, most of the cells will die unless the animal engages in some kind of effortful learning experience when the cells are about one week of age. If learning does occur, the new cells become incorporated into brain circuits used for learning. In turn, some processes of learning and mental activity appear to depend on their presence. In this review, we discuss the now rather extensive literature showing that new neurons are kept alive by effortful learning, a process that involves concentration in the present moment of experience over some extended period of time. As these thought processes occur, endogenous patterns of rhythmic electrophysiological activity engage the new cells with cell networks that already exist in the hippocampus and at efferent locations. Concurrent and synchronous activity provides a mechanism whereby the new neurons become integrated with the other neurons. This integration allows the present experience to become integrated with memories from the recent past in order to learn and predict when events will occur in the near future. In this way, neurogenesis and learning interact to maintain a fit brain.

New neurons are produced each day in the hippocampus through the process of neurogenesis. Both mental and physical training can modify this process by increasing the number of new cells that mature into functional neurons in the adult brain. However, the mechanisms whereby these increases occur are not necessarily the same. Physical activity, especially aerobic exercise greatly increases the number of new neurons that are produced in the hippocamal formation. In contrast, mental training via skill learning increases the numbers that survive, particularly when the training goals are challenging. Both manipulations can increase cognitive performance in the future, some of which are reportedly mediated by the presence of new neurons in the adult hippocampus. Based on these data, we suggest that a combination of mental and physical training, referred to here as MAP training, is more beneficial for neuronal recruitment and overall mental health than either activity alone.

Learning increases the number of immature neurons that survive and mature in the adult hippocampus (Gould et al., 1999). One week old cells are more likely to survive in response to learning than cells in animals that are exposed to training but do not learn (Shors, 2009). Because neurogenesis is an ongoing and overlapping process, it is possible that learning differentially affects new cells as a function of their maturity. To address this issue, we examined the effects of associative learning on the survival of cells at different stages of development. Training did not alter the number of cells that were produced and present during the training experience. Cells that were 1-2 weeks of age at the time of training remained in the hippocampus several weeks later but cells that were young or older did not. In contrast, cells that were produced during training were less likely to survive when compared to cells in untrained animals. Additionally, the number of cells that were generated after learning in trained animals was not different from untrained animals. Finally, survival was not increased if the association was reacquired and expressed when the cells were about one week old. Together, these results indicate that new neurons are rescued from death by initial acquisition, not the expression or reacquisition, of an associative memory and only during a critical period. Overall, these results suggest the presence of a feedback system, which controls how many new neurons become incorporated into the adult brain in response to learning.

Learning increases neurogenesis by increasing the survival of new cells generated in the adult hippocampal formation [Shors, T. J. Saving new brain cells. Scientific American, 300, 46-52, 2009]. However, only some types of learning are effective. Recent studies demonstrate that animals that learn the conditioned response (CR) but require more trials to do so retain more new neurons than animals that quickly acquire the CR or that fail to acquire the CR. In these studies, task parameters were altered to modify the number of trials required to learn a CR. Here, we asked whether pharmacological manipulations that prevent or facilitate learning would decrease or increase, respectively, the number of cells that remain in the hippocampus after training. To answer this question, we first prevented learning with the competitive N-methyl-d-aspartate (NMDA) receptor antagonist (RS)-3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid. As a consequence, training did not increase cell survival. Second, we facilitated learning with the cognitive enhancer d-cycloserine, which increases NMDA receptor activity via its actions at the glycine binding site. Administration of d-cycloserine each day before training increased the number of learned responses and the number of cells that survived. All animals that learned the CR retained more of the new cells, but those that learned very quickly retained fewer than those that required more training trials to learn. Together, these results demonstrate that NMDA receptor activation modifies learning and as a consequence alters the number of surviving cells in the adult hippocampus.

The dentate gyrus is a major site of plasticity in the adult brain, giving rise to thousands of new neurons every day, through the process of adult neurogenesis. Although the majority of these cells die within two weeks of their birth, they can be rescued from death by various forms of learning. Successful acquisition of select types of associative and spatial memories increases the number of these cells that survive. Here, we investigated the possibility that an entirely different form of learning, physical skill learning, could rescue new hippocampal cells from death. To test this possibility, rats were trained with a physically-demanding and technically-difficult version of a rotarod procedure. Acquisition of the physical skill greatly increased the number of new hippocampal cells that survived. The number of surviving cells positively correlated with performance on the task. Only animals that successfully mastered the task retained the cells that would have otherwise died. Animals that failed to learn, and those that did not learn well did not retain any more cells than those that were untrained. Importantly, acute voluntary exercise in activity wheels did not increase the number of surviving cells. These data suggest that acquisition of a physical skill can increase the number of surviving hippocampal cells. Moreover, learning an easier version of the task did not increase cell survival. These results are consistent with previous reports revealing that learning only rescues new neurons from death when acquisition is sufficiently difficult to achieve. Finally, complete hippocampal lesions did not disrupt acquisition of this physical skill. Therefore, physical skill training that does not depend on the hippocampus can effectively increase the number of surviving cells in the adult hippocampus, the vast majority of which become mature neurons.