NR2B-Dependent Plasticity of Adult-Born Granule Cells is Necessary for Context Discrimination

被引:134
作者
Kheirbek, Mazen A. [1 ,2 ,4 ]
Tannenholz, Lindsay [3 ,4 ]
Hen, Rene [1 ,2 ,3 ,4 ]
机构
[1] Columbia Univ, Dept Neurosci, New York, NY 10032 USA
[2] Columbia Univ, Dept Psychiat, New York, NY 10032 USA
[3] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA
[4] New York State Psychiat Inst & Hosp, Div Integrat Neurosci, New York, NY 10032 USA
关键词
NEWLY GENERATED NEURONS; HIPPOCAMPAL NEUROGENESIS; SYNAPTIC PLASTICITY; OBJECT RECOGNITION; DENTATE GYRUS; PATTERN SEPARATION; INTEGRATION; FLUOXETINE; CORTEX; MEMORY;
D O I
10.1523/JNEUROSCI.1692-12.2012
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
Adult-generated granule cells (GCs) in the dentate gyrus (DG) exhibit a period of heightened plasticity 4-6 weeks postmitosis. However, the functional contribution of this critical window of plasticity to hippocampal neurogenesis and behavior remains unknown. Here, we show that deletion of NR2B-containing NMDA receptors from adult-born GCs impairs a neurogenesis-dependent form of LTP in the DG and reduces dendritic complexity of adult-born GCs, but does not impact their survival. Mice in which the NR2B-containing NMDA receptor was deleted from adult-born GCs did not differ from controls in baseline anxiety-like behavior or discrimination of very different contexts, but were impaired in discrimination of highly similar contexts. These results indicate that NR2B-dependent plasticity of adult-born GCs is necessary for fine contextual discrimination and is consistent with their proposed role in pattern separation.
引用
收藏
页码:8696 / 8702
页数:7
相关论文
共 26 条
[1]
AUTORADIOGRAPHIC AND HISTOLOGICAL EVIDENCE OF POSTNATAL HIPPOCAMPAL NEUROGENESIS IN RATS [J].
ALTMAN, J ;
DAS, GD .
JOURNAL OF COMPARATIVE NEUROLOGY, 1965, 124 (03) :319-&
[2]
A Functional Role for Adult Hippocampal Neurogenesis in Spatial Pattern Separation [J].
Clelland, C. D. ;
Choi, M. ;
Romberg, C. ;
Clemenson, G. D., Jr. ;
Fragniere, A. ;
Tyers, P. ;
Jessberger, S. ;
Saksida, L. M. ;
Barker, R. A. ;
Gage, F. H. ;
Bussey, T. J. .
SCIENCE, 2009, 325 (5937) :210-213
[3]
Cull-Candy Stuart G, 2004, Sci STKE, V2004, pre16, DOI 10.1126/stke.2552004re16
[4]
Neurogenesis-Dependent and -Independent Effects of Fluoxetine in an Animal Model of Anxiety/Depression [J].
David, Denis J. ;
Samuels, Benjamin Adam ;
Rainer, Quentin ;
Wang, Jing-Wen ;
Marsteller, Douglas ;
Mendez, Indira ;
Drew, Michael ;
Craig, Douglas A. ;
Guiard, Bruno P. ;
Guilloux, Jean-Philippe ;
Artymyshyn, Roman P. ;
Gardier, Alain M. ;
Gerald, Christophe ;
Antonijevic, Irina A. ;
Leonardo, E. David ;
Hen, Rene .
NEURON, 2009, 62 (04) :479-493
[5]
4-to 6-week-old adult-born hippocampal neurons influence novelty-evoked exploration and contextual fear conditioning [J].
Denny, Christine A. ;
Burghardt, Nesha S. ;
Schachter, Daniel M. ;
Hen, Rene ;
Drew, Michael R. .
HIPPOCAMPUS, 2012, 22 (05) :1188-1201
[6]
Experience Dictates Stem Cell Fate in the Adult Hippocampus [J].
Dranovsky, Alex ;
Picchini, Alyssa M. ;
Moadel, Tiffany ;
Sisti, Alexander C. ;
Yamada, Atsushi ;
Kimura, Shioko ;
Leonardo, E. David ;
Hen, Rene .
NEURON, 2011, 70 (05) :908-923
[7]
Effects of chronic fluoxetine in animal models of anxiety and depression [J].
Dulawa, SC ;
Hollick, KA ;
Gundersen, B ;
Hen, R .
NEUROPSYCHOPHARMACOLOGY, 2004, 29 (07) :1321-1330
[8]
Uncoupling Dendrite Growth and Patterning: Single-Cell Knockout Analysis of NMDA Receptor 2B [J].
Espinosa, J. Sebastian ;
Wheeler, Damian G. ;
Tsien, Richard W. ;
Luo, Liqun .
NEURON, 2009, 62 (02) :205-217
[9]
A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain [J].
Ge, Shaoyu ;
Yang, Chih-hao ;
Hsu, Kuei-sen ;
Ming, Guo-li ;
Song, Hongjun .
NEURON, 2007, 54 (04) :559-566
[10]
GABA regulates synaptic integration of newly generated neurons in the adult brain [J].
Ge, SY ;
Goh, ELK ;
Sailor, KA ;
Kitabatake, Y ;
Ming, GL ;
Song, HJ .
NATURE, 2006, 439 (7076) :589-593