title: Distinct roles of NMDA receptors at different stages of granule cell development in the adult brain.
abstract: NMDA receptor (NMDAR)-dependent forms of synaptic plasticity are thought to underlie the assembly of developing neuronal circuits and to play a crucial role in learning and memory. It remains unclear how NMDAR might contribute to the wiring of adult-born granule cells (GCs). Here we demonstrate that nascent GCs lacking NMDARs but rescued from apoptosis by overexpressing the pro-survival protein Bcl2 were deficient in spine formation. Insufficient spinogenesis might be a general cause of cell death restricted within the NMDAR-dependent critical time window for GC survival. NMDAR loss also led to enhanced mushroom spine formation and synaptic AMPAR activity throughout the development of newborn GCs. Moreover, similar elevated synapse maturation in the absence of NMDARs was observed in neonate-generated GCs and CA1 pyramidal neurons. Together, these data suggest that NMDAR operates as a molecular monitor for controlling the activity-dependent establishment and maturation rate of synaptic connections between newborn neurons and others.
authors.affiliation: Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yangling
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, United States.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Toni
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, United States.
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology*; D002454:Cell Differentiation; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate
keywords: NMDA receptor; adult neurogenesis; mouse; neuroscience; spine