title: NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus.
abstract: New neurons are continuously integrated into existing neural circuits in adult dentate gyrus of the mammalian brain. Accumulating evidence indicates that these new neurons are involved in learning and memory. A substantial fraction of newly born neurons die before they mature and the survival of new neurons is regulated in an experience-dependent manner, 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.
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Tashiro
authors.forename: Vladislav M
authors.initials: VM
authors.lastname: Sandler
authors.forename: Nicolas
authors.initials: N
authors.lastname: Toni
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhao
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D016923:Cell Death; D002470:Cell Survival; D018891:Dentate Gyrus / Q000166:cytology* / Q000502:physiology; D066298:In Vitro Techniques; D007858:Learning / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate