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

摘要

Learning increases neurogenesis by increasing the survival ofnnew cells generated in the adult hippocampal formation [Shors,nT. J. Saving new brain cells. Scientific American, 300, 46–52,n2009]. However, only some types of learning are effective. Recentnstudies demonstrate that animals that learn the conditionednresponse (CR) but require more trials to do so retain more newnneurons than animals that quickly acquire the CR or that fail tonacquire the CR. In these studies, task parameters were altered tonmodify the number of trials required to learn a CR. Here, wenasked whether pharmacological manipulations that prevent ornfacilitate learning would decrease or increase, respectively,nthe number of cells that remain in the hippocampus after training.nTo answer this question, we first prevented learning withnthe competitive N-methyl-D-aspartate (NMDA) receptor antagonistn(RS)-3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid.nAs a consequence, training did not increase cell survival. Second,nwe facilitated learning with the cognitive enhancer D-cycloserine,nwhich increases NMDA receptor activity via its actions at thenglycine binding site. Administration of D-cycloserine each daynbefore training increased the number of learned responses andnthe number of cells that survived. All animals that learned thenCR retained more of the new cells, but those that learned verynquickly retained fewer than those that required more trainingntrials to learn. Together, these results demonstrate that NMDAnreceptor activation modifies learning and as a consequence altersnthe number of surviving cells in the adult hippocampus.