Learning Increases the Survival of Newborn Neurons Provided That Learning Is Difficult to Achieve and Successful

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.