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

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Abstract
New neurons are continuously integrated into existing neural circuits in adult dentate gyrus of the mammalian brain1,2,3,4. Accumulating evidence indicates that these new neurons are involved in learning and memory5,6,7,8. A substantial fraction of newly born neurons die before they mature9,10 and the survival of new neurons is regulated in an experience-dependent manner5,6,11, 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.