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
相关论文
共 50 条
  • [1] Lentiviral silencing of GSK-3β in adult dentate gyrus impairs contextual fear memory and synaptic plasticity
    Chew, Benjamin
    Ryu, Jae Ryun
    Ng, Teclise
    Ma, Dongliang
    Dasgupta, Ananya
    Neo, Sin Hui
    Zhao, Jing
    Zhong, Zhong
    Bichler, Zoe
    Sajikumar, Sreedharan
    Goh, Eyleen L. K.
    FRONTIERS IN BEHAVIORAL NEUROSCIENCE, 2015, 9
  • [2] Adiponectin modulates synaptic plasticity in hippocampal dentate gyrus
    Pousti, Farideh
    Ahmadi, Ramesh
    Mirahmadi, Fatemeh
    Hosseinmardi, Narges
    Rohampour, Kambiz
    NEUROSCIENCE LETTERS, 2018, 662 : 227 - 232
  • [3] Effects of adult neurogenesis on synaptic plasticity in the rat dentate gyrus
    Snyder, JS
    Kee, N
    Wojtowicz, JM
    JOURNAL OF NEUROPHYSIOLOGY, 2001, 85 (06) : 2423 - 2431
  • [4] Effects of lactate/pyruvate on synaptic plasticity in the hippocampal dentate gyrus
    Yang, B
    Sakurai, T
    Takata, T
    Yokono, K
    NEUROSCIENCE RESEARCH, 2003, 46 (03) : 333 - 337
  • [5] Intermittent Hypoxia Disrupts Adult Neurogenesis and Synaptic Plasticity in the Dentate Gyrus
    Khuu, Maggie A.
    Pagan, Chelsea M.
    Nallamothu, Thara
    Hevner, Robert F.
    Hodge, Rebecca D.
    Ramirez, Jan-Marino
    Garcia, Alfredo J., III
    JOURNAL OF NEUROSCIENCE, 2019, 39 (07): : 1320 - 1331
  • [6] Inhibiting 11β-hydroxysteroid dehydrogenase type 1 prevents stress effects on hippocampal synaptic plasticity and impairs contextual fear conditioning
    Sarabdjitsingh, R. Angela
    Zhou, Ming
    Yau, Joyce L. W.
    Webster, Scott P.
    Walker, Brian R.
    Seckl, Jonathan R.
    Joels, Marian
    Krugers, Harm J.
    NEUROPHARMACOLOGY, 2014, 81 : 231 - 236
  • [7] Chronic Intermittent Hypoxia (CIH) Impairs Neurogenesis and Alters Paired Pulse Synaptic Plasticity In the Dentate Gyrus of Hippocampus
    Khuu, Maggie
    Hodge, Rebecca
    Ramirez, Jan-Marino
    Garcia, Alfredo, III
    FASEB JOURNAL, 2015, 29
  • [8] Developmental lead exposure impairs contextual fear conditioning and reduces adult hippocampal neurogenesis in the rat brain
    Jaako-Movits, K
    Zharkovsky, T
    Romantchik, O
    Jurgenson, M
    Merisalu, E
    Heidmets, LT
    Zharkovsky, A
    INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 2005, 23 (07) : 627 - 635
  • [9] Enhanced dentate gyrus synaptic plasticity but reduced neurogenesis in a mouses model of amyloidosis
    Poirier, Raphael
    Veltman, Inge
    Pflimlin, Marie Claire
    Knoflach, Frederic
    Metzger, Friedrich
    NEUROBIOLOGY OF DISEASE, 2010, 40 (02) : 386 - 393
  • [10] Enhancement of dentate gyrus neurogenesis, dendritic and synaptic plasticity and memory by a neurotrophic peptide
    Chohan, Muhammad Omar
    Li, Bin
    Blanchard, Julie
    Tung, Yunn-Chyn
    Heaney, Agnes T.
    Rabe, Ausma
    Iqbal, Khalid
    Grundke-Iqbal, Inge
    NEUROBIOLOGY OF AGING, 2011, 32 (08) : 1420 - 1434