NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus

New neurons are continuously integrated into existing neural circuits in adult dentate gyrus of the mammalian brain(1-4). Accumulating evidence indicates that these new neurons are involved in learning and memory(5-8). A substantial fraction of newly born neurons die before they mature(9,10) and the survival of new neurons is regulated in an experience-dependent manner(5,6,11), raising the possibility that the selective survival or death of new neurons has a direct role in a process of learning and memory such as information storage - through the information-specific construction of new circuits. However, a critical assumption of this hypothesis is that the survival or death decision of new neurons is information-specific. Because neurons receive their information primarily through their input synaptic activity, we investigated whether the survival of new neurons is regulated by input activity in a cell-specific manner. Here we developed a retrovirus-mediated, single-cell gene knockout technique in mice and showed that the survival of new neurons is competitively regulated by their own NMDA-type glutamate receptor during a short, critical period soon after neuronal birth. This finding indicates that the survival of new neurons and the resulting formation of new circuits are regulated in an input-dependent, cell-specific manner. Therefore, the circuits formed by new neurons may represent information associated with input activity within a short time window in the critical period. This information-specific addition of new circuits through selective survival or death of new neurons may be a unique attribute of new neurons that enables them to play a critical role in learning and memory.