Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus

被引:793
|
作者
Saxe, Michael D.
Battaglia, Fortunato
Wang, Jing-Wen
Malleret, Gael
David, Denis J.
Monckton, James E.
Garcia, A. Denise R.
Sofroniew, Michael V.
Kandel, Eric R.
Santarelli, Luca
Hen, Rene [1 ]
Drew, Michael R.
机构
[1] Columbia Univ, Ctr Neurobiol & Behav, 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] Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA
[5] Univ Paris 11, Fac Pharm, Neuropharmacol Lab, F-92296 Chatenay Malabry, France
[6] Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA
[7] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA
关键词
long-term potentiation; learning; memory;
D O I
10.1073/pnas.0607207103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Although hippocampal neurogenesis has been described in many adult mammals, the functional impact of this process on physiology and behavior remains unclear. in the present study, we used two independent methods to ablate hippocampal neurogenesis and found that each procedure caused a limited behavioral deficit and a loss of synaptic plasticity within the dentate gyrus. Specifically, focal X irradiation of the hippocampus or genetic ablation of glial fibrillary acidic protein-positive neural progenitor cells impaired contextual fear conditioning but not clued conditioning. Hippocampal-dependent spatial learning tasks such as the Morris water maze and Y maze were unaffected. These findings show that adult-born neurons make a distinct contribution to some but not all hippocampal functions. In a parallel set of experiments, we show that long-term potentiation elicited in the dentate gyrus in the absence of GABA blockers requires the presence of new neurons, as it is eliminated by each of our ablation procedures. These data show that new hippocampal neurons can be preferentially recruited over mature granule cells in vitro and may provide a framework for how this small cell population can influence behavior.
引用
收藏
页码:17501 / 17506
页数:6
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