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系統識別號 U0026-2406201416592900
論文名稱(中文) 探討壓力對於海馬迴神經突觸可塑性以及新生神經細胞之影響
論文名稱(英文) The study of stress on hippocampal synaptic plasticity and adult neurogenesis
校院名稱 成功大學
系所名稱(中) 基礎醫學研究所
系所名稱(英) Institute of Basic Medical Sciences
學年度 102
學期 2
出版年 103
研究生(中文) 陳建仲
研究生(英文) Chien-Chung Chen
學號 S58971471
學位類別 博士
語文別 英文
論文頁數 97頁
口試委員 指導教授-許桂森
口試委員-郭余民
口試委員-曾淑芬
口試委員-黃阿敏
中文關鍵字 壓力,海馬迴  突觸可塑性  神經新生 
英文關鍵字 Stress  hippocampus  Synaptic plasticity  Neurogenesis 
學科別分類
中文摘要 不論是動物實驗或者臨床研究已經有許多的證據顯示充滿壓力的生活因子會對於認知功能以及行為表現產生嚴重的影響,而在海馬迴神經細胞本身神經突觸可塑性所產生的影響,然而對於其中細胞以及分子機制的改變至今仍然不清楚。因此我們研究了對於壓力敏感的海馬迴三突觸循環結構中的調控者,其中苔狀纖維(mossy fiber)是一個具有特殊分子機制以及高可塑性的一部分,當一個無法預測的急性壓力,會造成一個明顯的苔狀纖維長期增益現象(LTP)的抑制,並且發現,主要是因為壓力所促進了環腺苷酸(cAMP)專一的磷酸二酯酶(PDE4)的活性所造成的。
而慢性壓力的暴露則會抑制神經新生作用,但是對於其發育過程的影響卻仍然未知的,因此我們試著透過慢性社會壓力 (CSDS) 模式,並且利用反轉錄病毒標記新生神經細胞來研究各個時期的發育,去探討壓力對於發育過程的型態以及電生理特性的成熟化所造成的影響。我們所使用的C57BL/6小鼠可根據其行為模式的表現以區分為耐受性高以及耐受性低的組別,而兩組老鼠也在尾巴懸吊測試以及糖水偏好測試相對表現了不同程度的憂鬱行為。不過令人意外的是,這兩組小鼠在於新生神經細胞的存活率以及樹突複雜程度的表現卻不若行為一般有差異,同樣受到抑制,不過並沒有影響新生神經細胞在顆粒細胞層的分布。反轉錄病毒所標記的不同時間點的新生神經細胞,其基礎電生理活性並不會受到壓力刺激所影響,不過我們觀察到了一種對於其N-甲基-D-天冬氨酸受體 (NMDAR) 在發育過程中,由含有2B型態轉換為含有2A型態的加速過程,其中對於細胞表現長期增益現象 (LTP) 的表現具有非常大的影響。更進一步我們透過調控神經限制因子 (REST) 去改變這種受體轉換的過程,而了解慢性壓力刺激會改變新生神經細胞成熟的過程,透過這種神經限制因子的表現,而在壓力刺激下生存下來。
英文摘要 More evidence from animal and human study indicates that stressful life event may result in massive influence on cognitive function and behavior change based on the synaptic plasticity of hippocampus. However the underlying cellular and molecular mechanism by which stress exerts it effects on behavior remain unclear. Here we demonstrate several key regulator of hippocampal trisynaptic circuit which is sensitive to stress response. The mossy fiber synapse onto hippocampal CA3 neurons shows unique molecular features and a wide dynamic range of plasticity. An acute unpredictable and inescapable restraint tail-shock stress showed a marked impairment of long-term potentiation (LTP) expression in this region through a interruption of a cAMP-specific PDE4 activity.
Chronic stress has been found to suppress adult neurogenesis, and we examined the influence of chronic social defeat stress (CSDS) on the morphological and electrophysiological properties of retrovirally-labeled adult-born dentate granule cells (DGCs) at different maturation stages. Our results confirm that C57BL/6 inbred mouse strain subjected to CSDS can be separated into susceptible and unsusceptible subpopulations that displayed different levels of depressive-like behaviors but identical reductions in the survival and dendritic complexity of adult-born DGCs. Combining electrophysiology with retrovirus- mediated birthdating and labeling, we find that although CSDS does not alter the intrinsic electrophysiological properties and synaptic transmission of surviving adult-born DGCs, it accelerates the developmental switch of synaptic N-methyl-D- aspartate receptors (NMDARs) from predominance of GluN2B- to GluN2A- containing receptors, which, in turn, transforms the immature synapse of adult-born DGCs from one that exhibits enhanced LTP to one in which has normal levels of LTP. Furthermore, knockdown of the repressor element 1 silencing transcription factor (REST) in adult-born DGCs prevented CSDS-induced accelerated developmental switch of NMDAR subunit composition. Together, these results reveal a novel role for CSDS in regulating adult neurogenesis and suggest that CSDS may accelerate the rate of maturation of surviving adult-born DGCs through the expression of REST to overcome the neurotoxic effect.
論文目次 摘要‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧I
Abstract‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧II
致謝‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧IV
Content‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧V
List of figures‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧IX
Abbreviations‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧XI
Chapter I:Introduction‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧1
1.1 Acute stress and chronic stress
1.2 Hypothalamic-pituitary-adrenal axis
1.3 Stress and synaptic plasticity in hippocampus
1.4 Stress and adult neurogenesis
1.5 Adult neurogenesis and neuronal plasticity
1.6 N-Methyl-D-aspartate receptor in neuronal maturation
1.7 Repressor element 1 silencing transcription factor (REST) in adult neurognesis regulation
1.8 Specific aims
Chapter II:Materials and methods‧‧‧‧‧‧‧‧‧‧9
2.1 Animal
2.2 Stress protocol
2.2.1 Acute stress
2.2.2 Chronic social defeat stress
2.3 Adrenalectomy and corticosterone replacement
2.4 Plasma corticosterone assay
2.5 Behavioral test
2.5.1 Tail suspension test
2.5.2 Sucrose preference test
2.5.3 Contextual discrimination fear conditioning between contexts
2.6 cAMP assay
2.7 Phosphodiesterase activity assay
2.8 BrdU labeling newborn neurons
2.9 Retrovirus production, stereotaxic injection and analysis
2.10 Electrophysiological recordings
2.10.1 Extracellular recordings
2.10.2 Whole-cell patch-clamp
2.11.1 Preparation of synaptosomes
2.12 Pharmacological drugs
2.13 Statistical analysis
Chapter III:Results‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧22
3.1 Effects of stress on mossy fiber synaptic transmission and frequency facilitation
3.2 Stress impairs mossy fiber LTP
3.3 Putative mechanisms of the effect of stress on mossy fiber LTP
3.4 Stress increases PDE4 activity to enhance cAMP degradation
3.5 Individual differences in responses to CSDS
3.6 CSDS reduces survival of adult-born DGCs in both susceptible and unsusceptible mice
3.7 Contextual discrimination is impaired in CSDS mice for a highly similar context pair
3.8 CSDS alters dendritic morphogenesis of adult-born DGCs in both susceptible and unsusceptible mice
3.9 CSDS facilitates the developmental switch in synaptic plasticity of adult-born DGCs
3.10 CSDS reduces synaptic GluN2B subunit expression in adult-born DGCs via an REST-dependent mechanism
Chapter IV:Discussion‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧40
4.1 The effect of acute stress on hippocampal CA3 synaptic plasticity through regulate PDE4 activity
4.2 Chronic social defeat stress alters the maturation stage of adult neurogenesis through a REST dependent regulation
Chapter V:Conclusion‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧48
Chapter VI:Figures and ledgends‧‧‧‧‧‧‧‧‧‧52
Chapter VII:References‧‧‧‧‧‧‧‧‧‧‧‧‧‧83
Chapter VIII:Publications‧‧‧‧‧‧‧‧‧‧‧‧‧97
參考文獻 Anacker C, Cattaneo A, Musaelyan K, Zunszain PA, Horowitz M, Molteni R, Luoni A, Calabrese F, Tansey K, Gennarelli M, Thuret S, Price J, Uher R, Riva MA, Pariante CM (2013) Role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis. Proc Natl Acad Sci U S A 110:8708-8713.
Ahmed T, Frey JU, Korz V (2006) Long-term effects of brief acute stress on cellular signaling and hippocampal LTP. J Neurosci 26:3951-3958.
Alzheimer C, Röhrenbeck J, ten Bruggencate G (1991) Adenosine depresses induction of LTP at the mossy fiber-CA3 synapse in vitro. Brain Res 543:163-165.
Avgustinovich DF, Gorbach OV, Kudryavtseva NN (1997) Comparative analysis of anxiety-like behavior in partition and plus-maze tests after agonistic interactions in mice. Physiol Behav 61:37-43.
Bain MJ, Dwyer SM, Rusak B (2004) Restraint stress affects hippocampal cell proliferation differently in rats and mice. Neurosci Lett 368:7-10.
Baillie GS, MacKenzie SJ, McPhee I, Houslay MD (2000) Sub-family selective actions in the ability of Erk2 MAP kinase to phosphorylate and regulate the activity of PDE4 cyclic AMP-specific phosphodiesterases. Br J Pharmacol 131:811-819.
Bains JS, Longacher JM, Staley KJ (1999) Reciprocal interactions between CA3 network activity and strength of recurrent collateral synapses. Nat Neurosci 2: 720–726.
Ballas, Z.K., Krieg, A.M., Warren, T., Rasmussen, W., Davis, H.L., Waldschmidt, M., and Weiner, G.J. (2001). Divergent therapeutic and immunologic effects of oligodeoxynucleotides with distinct CpG motifs. J Immunol 167, 4878-4886.

Bruns RF, Lu GH, Pugsley TA (1986) Characterization of the A2 adenosine receptor labeled by [3H]NECA in rat striatal membranes. Mol Pharmacol 29:331-346.
Barria A, Malinow R (2005) NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII. Neuron 48:289-301.
Barth AL, Malenka RC (2001) NMDAR EPSC kinetics do not regulate the critical period for LTP at thalamocortical synapses. Nat Neurosci 4:235-236.
Berton O, Covington HE 3rd, Ebner K, Tsankova NM, Carle TL, Ulery P, Bhonsle A, Barrot M, Krishnan V, Singewald GM, Singewald N, Birnbaum S, Neve RL, Nestler EJ (2007) Induction of FosB in the periaqueductal gray by stress promotes active coping responses. Neuron 55:289-300.
Brummelte S, Galea LA (2010) Chronic corticosterone during pregnancy and postpartum affects maternal care, cell proliferation and depressive-like behavior in the dam. Horm Behav 58:769-779.
Cameron HA, McKay RD (2001) Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J Comp Neurol 435:406-417.
Castillo PE, Janz R, Südhof TC, Tzounopoulos T, Malenka RC, Nicoll RA (1997) Rab3A is essential for mossy fibre long-term potentiation in the hippocampus. Nature 388:590-593.
Chen YL, Huang CC, Hsu KS (2001) Time-dependent reversal of long-term potentiation by low-frequency stimulation at the hippocampal mossy fiber-CA3 synapses. J Neurosci 21:3705-3714.
Cherry JA, Davis RL (1999) Cyclic AMP phosphodiesterases are localized in regions of the mouse brain associated with reinforcement, movement, and affect. J Comp Neurol 407:287-301.
Chong, J.A., Tapia-Ramirez, J., Kim, S., Toledo-Aral, J.J., Zheng, Y., Boutros, M.C., Altshuller, Y.M., Frohman, M.A., Kraner, S.D., and Mandel, G. (1995). REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons. Cell 80, 949-957.
Coffin VL, Spealman RD (1989) Psychomotor-stimulant effects of 3-isobutyl-1-methylxanthine: comparison with caffeine and 7-(2-chloroethyl) theophylline. Eur J Pharmacol 170:35-40.
Cull-Candy SG, Leszkiewicz DN (2004) Role of distinct NMDA receptor subtypes at central synapses. Sci STKE 2004:re16.
Czéh B, Müller-Keuker JI, Rygula R, Abumaria N, Hiemke C, Domenici E, Fuchs E (2007) Chronic social stress inhibits cell proliferation in the adult medial prefrontal cortex: hemispheric asymmetry and reversal by fluoxetine treatment. Neuropsychopharmacology 32:1490-1503.
De Lima, T.C., and Rae, G.A. (1991). Effects of cold-restraint and swim stress on convulsions induced by pentylenetetrazol and electroshock: influence of naloxone pretreatment. Pharmacology, biochemistry, and behavior 40, 297-300.
Diamond DM, Bennett MC, Fleshner M, Rose GM (1992) Inverted-U relationship between the level of peripheral corticosterone and the magnitude of hippocampal primed burst potentiation. Hippocampus 2:421-430.
Diamond, D.M., Fleshner, M., Ingersoll, N., and Rose, G.M. (1996). Psychological stress impairs spatial working memory: relevance to electrophysiological studies of hippocampal function. Behavioral neuroscience 110, 661-672.
Diamond DM, Park CR, Campbell AM, Woodson JC (2004) Competitive interactions between endogenous LTD and LTP in the hippocampus underlie the storage of emotional memories and stress-induced amnesia. Hippocampus 15:1006-1025.
Duan X, Chang JH, Ge S, Faulkner RL, Kim JY, Kitabatake Y, Liu XB, Yang CH, Jordan JD, Ma DK, Liu CY, Ganesan S, Cheng HJ, Ming GL, Lu B, Song H (2007) Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain. Cell 130:1146-1158.
Duman RS, Nakagawa S, Malberg J (2001) Regulation of adult neurogenesis by antidepressant treatment. Neuropsychopharmacology 25:836-844.
Espósito MS, Piatti VC, Laplagne DA, Morgenstern NA, Ferrari CC, Pitossi FJ, Schinder AF (2005) Neuronal differentiation in the adult hippocampus recapitulates embryonic development. J Neurosci 25:10074-10086.
Ferragud A, Haro A, Sylvain A, Velázquez-Sánchez C, Hernández-Rabaza V, Canales JJ (2010) Enhanced habit-based learning and decreased neurogenesis in the adult hippocampus in a murine model of chronic social stress. Behav Brain Res 210:134-139.
Franklin K, and Paxinos G (2008) The mouse brain in stereotaxic coordinates. San Diego: Elsevier Academic Press.
Fredholm BB, Dunwiddie TV (1988) How does adenosine inhibit transmitter release? Trends Pharmacol Sci 9:130-134.
Gage FH (2000) Mammalian neural stem cells. Science 287:1433-1438.
Gao Z, Ure K, Ding P, Nashaat M, Yuan L, Ma J, Hammer RE, Hsieh J (2011) The master negative regulator REST/NRSF controls adult neurogenesis by restraining the neurogenic program in quiescent stem cells. J Neurosci 31:9772-9786.
Ge S, Goh EL, Sailor KA, Kitabatake Y, Ming GL, Song H (2006) GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 439:589-593.
Ge S, Yang CH, Hsu KS, Ming GL, Song H (2007) A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain. Neuron 54:559-566.
Gould E, McEwen BS, Tanapat P, Galea LA, Fuchs E (1997) Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J Neurosci 17:2492-2498.
Gould E, Tanapat P, McEwen BS, Flügge G, Fuchs E (1998) Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc Natl Acad Sci U S A 95:3168-3171.
Griffith WH (1990) Voltage-clamp analysis of posttetanic potentiation of the mossy fiber to CA3 synapse in hippocampus. J Neurophysiol 63:491-501.
Gundlfinger A, Bischofberger J, Johenning FW, Torvinen M, Schmitz D, Breustedt J (2007) Adenosine modulates transmission at the hippocampal mossy fiber synapse via direct inhibition of presynaptic calcium channels. J Physiol 582:263-277.
Harris EW, Cotman CW (1986) Long-term potentiation of guinea pig mossy fiber responses is not blocked by N-methyl D-aspartate antagonists. Neurosci Lett 70:132-137.
Heine VM, Maslam S, Joëls M, Lucassen PJ (2004) Prominent decline of newborn cell proliferation, differentiation, and apoptosis in the aging dentate gyrus, in absence of an age-related hypothalamus-pituitary-adrenal axis activation. Neurobiol Aging 25:361-375.
Hill MN, Kambo JS, Sun JC, Gorzalka BB, Galea LA (2006) Endocannabinoids modulate stress-induced suppression of hippocampal cell proliferation and activation of defensive behaviours. Eur J Neurosci 24:1845-1849.
Huang CC, Chen YL, Liang YC, Hsu KS (2002) Role for cAMP and protein phosphatase in the presynaptic expression of mouse hippocampal mossy fiber depotentiation. J Physiol 543:767-778.
Huang CC, Yang CH, Hsu KS (2005) Do stress and long-term potentiation share the same molecular mechanisms? Mol Neurobiol 32:223-235.
Huang YF, Yang CH, Huang CC, Hsu KS (2012) Vascular endothelial growth factor-dependent spinogenesis underlies antidepressant-like effects of enriched environment. J Biol Chem 287:40938-40955.
Huang YY, Li XC, Kandel ER (1994) cAMP contributes to mossy fiber LTP by initiating both a covalently mediated early phase and macromolecular synthesis-denpendent late phase. Cell 79:69-79.
Jacobson L, Sapolsky R (1991) The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis. Endocr Rev 12:118-134.
Jessberger, S., Zhao, C., Toni, N., Clemenson, G.D., Jr., Li, Y., and Gage, F.H. (2007). Seizure-associated, aberrant neurogenesis in adult rats characterized with retrovirus-mediated cell labeling. The Journal of neuroscience : the official journal of the Society for Neuroscience 27, 9400-9407.
Kavushansky A, Vouimba RM, Cohen H, Richter-Levin G (2006) Activity and plasticity in the CA1, the dentate gyrus, and the amygdala following controllable vs. uncontrollable water stress. Hippocampus 16:35-42.
Kawamura Y, Manita S, Nakamura T, Inoue M, Kudo Y, Miyakawa H (2004) Glutamate release increases during mossy-CA3 LTP but not during Schaffer-CA1 LTP. Eur J Neurosci 19:1591-1600.
Kempermann G, Kuhn HG, Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386:493-495.
Kempermann G, Gast D, Kronenberg G, Yamaguchi M, Gage FH (2003) Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice. Development 130:391-399.
Kempermann G, Jessberger S, Steiner B, Kronenberg G (2004) Milestones of neuronal development in the adult hippocampus. Trends Neurosci 27:447-452.
Kerr DS, Huggett AM, Abraham WC (1994) Modulation of hippocampal long-term potentiation and long-term depression by corticosteroid receptor activation. Psychobiology 22:123-133.
Kheirbek MA, Tannenholz L, Hen R (2012) NR2B-dependent plasticity of adult-born granule cells is necessary for context discrimination. J Neurosci 32:8696-8702.
Kim JJ, Diamond DM (2002) The stressed hippocampus, synaptic plasticity and lost memories. Nat Rev Neurosci 3:453-462.
Kim JJ, Foy MR, Thompson RF (1996) Behavioral stress modifies hippocampal plasticity through N-methyl-D-aspartate receptor activation. Proc Natl Acad Sci USA 93:4750-4753.
Kim JJ, Yoon KS (1998) Stress: metaplastic effects in the hippocampus. Trends Neurosci 21:505-509.
Korz V, Frey JU (2003) Stress-related modulation of hippocampal long-term potentiation in rats: Involvement of adrenal steroid receptors. J Neurosci 23:7281-7287.
Korz V, Frey JU (2005) Bidirectional modulation of hippocampal long-term potentiation under stress and no-stress conditions in basolateral amygdala-lesioned and intact rats. J Neurosci 25:7393-7400.
Krishnan V, Han MH, Graham DL, Berton O, Renthal W, Russo SJ, Laplant Q, Graham A, Lutter M, Lagace DC, Ghose S, Reister R, Tannous P, Green TA, Neve RL, Chakravarty S, Kumar A, Eisch AJ, Self DW, Lee FS, Tamminga CA, Cooper DC, Gershenfeld HK, Nestler EJ (2007) Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 131:391-404.
Krishnan V, Berton O, Nestler E (2008) The use of animal models in psychiatric research and treatment. Am J Psychiatry 165:1109.
Lagace DC, Donovan MH, DeCarolis NA, Farnbauch LA, Malhotra S, Berton O, Nestler EJ, Krishnan V, Eisch AJ (2010) Adult hippocampal neurogenesis is functionally important for stress-induced social avoidance. Proc Natl Acad Sci U S A 107:4436-4441.
Laplagne DA, Espósito MS, Piatti VC, Morgenstern NA, Zhao C, van Praag H, Gage FH, Schinder AF (2006) Functional convergence of neurons generated in the developing and adult hippocampus. PLoS Biol 4:e409.
Latini S, Pedata F (2001) Adenosine in the central nervous system: release mechanisms and extracellular concentrations. J Neurochem 79:463-484.
Lee KJ, Kim SJ, Kim SW, Choi SH, Shin YC, Park SH, Moon BH, Cho E, Lee MS, Choi SH, Chun BG, Shin KH (2006) Chronic mild stress decreases survival, but not proliferation, of new-born cells in adult rat hippocampus. Exp Mol Med 38:44-54.
Lehmann ML, Brachman RA, Martinowich K, Schloesser RJ, Herkenham M (2013) Glucocorticoids orchestrate divergent effects on mood through adult neurogenesis. J Neurosci 33:2961-2972.
Lu KT, Gean PW (1999) Masking of forskolin-induced long-term potentiation by adenosine accumulation in area CA1 of the rat hippocampus. Neuroscience 88:69-78.
MacKenzie SJ, Baillie GS, McPhee I, Bolger GB, Houslay MD (2000) ERK2 mitogen-activated protein kinase binding, phosphorylation, and regulation of the PDE4D cAMP-specific phosphodiesterases. The involvement of COOH-terminal docking sites and NH2-terminal UCR regions. J Biol Chem 275:16609-16617.
McEwen BS (1999) Stress and hippocampal plasticity. Annu Rev Neurosci 22:105-122.
McEwen BS, Sapolsky RM (1995) Stress and cognitive function. Curr Opin Neurobiol 5:205-216.
Malberg JE, Duman RS (2003) Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology 28:1562-1571.
McNaughton BL (1980) Evidence for two physiologically distinct perforant pathways to the fascia dentata. Brain Res 199:1-19.
McPhee I, Cochran S, Houslay MD (2001) The novel long PDE4A10 cyclic AMP phosphodiesterase shows a pattern of expression within brain that is distinct from the long PDE4A5 and short PDE4A1 isoforms. Cell Signal 13:911-918.
Ming GL, Song H (2005) Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 28:223-250.
Ming GL, Song H (2011) Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 70:687-702.
Mirescu C, Peters JD, Gould E (2004) Early life experience alters response of adult neurogenesis to stress. Nat Neurosci 7:841-846.
Mitsuno K, Sasa M, Ishihara K, Ishikawa M, Kikuchi H (1994) LTP of mossy fiber-stimulated potentials in CA3 during learning in rats. Physiol Behav 55:633-638.
Mongiat LA, Espósito MS, Lombardi G, Schinder AF (2009) Reliable activation of immature neurons in the adult hippocampus. PLoS One 4:e5320.
Moore KA, Nicoll RA, Schmitz D (2003) Adenosine gates synaptic plasticity at hippocampal mossy fiber synapses. Proc Natl Acad Sci USA 100:14397-14402.
Nicoll RA, Malenka RC (1995) Contrasting properties of two forms of long-term potentiation in the hippocampus. Nature 377:115-118.
Nicoll RA, Schmitz D (2005) Synaptic plasticity at hippocampal mossy fibre synapses. Nat Rev Neurosci 6:863-876.
Ortiz J, Harris HW, Guitart X, Terwilliger RZ, Haycock JW, Nestler EJ (1995) Extracellular signal-regulated protein kinases (ERKs) and ERK kinase (MEK) in brain: regional distribution and regulation by chronic morphine. J Neurosci 15:1285-1297.
Otto C, Kovalchuk Y, Wolfer DP, Gass P, Martin M, Zuschratter W, Gröne HJ, Kellendonk C, Tronche F, Maldonado R, Lipp HP, Konnerth A, Schütz G (2001) Impairment of mossy fiber long-term potentiation and associative learning in pituitary adenylate cyclase activating polypeptide type I receptor-deficient mice. J Neurosci 21:5520-5527.
Palmer, G.C., Borrelli, A.R., Hudzik, T.J., and Sparber, S. (1998). Acute heat stress model of seizures in weanling rats: influence of prototypic anti-seizure compounds. Epilepsy research 30, 203-217.
Pavlides C, Watanabe Y, McEwen BS (1993) Effects of glucocorticoids on hippocampal long-term potentiation. Hippocampus 3:183-192.
Pavlides C, Nivón LG, McEwen BS (2002) Effects of chronic stress on hippocampal long-term potentiation. Hippocampus 12:245-257.
Pericic, D., Svob, D., Jazvinscak, M., and Mirkovic, K. (2000). Anticonvulsive effect of swim stress in mice. Pharmacology, biochemistry, and behavior 66, 879-886.
Pham K, Nacher J, Hof PR, McEwen BS (2003) Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus. Eur J Neurosci 17:879-886.
Piatti VC, Davies-Sala MG, Espósito MS, Mongiat LA, Trinchero MF, Schinder AF (2011) The timing for neuronal maturation in the adult hippocampus is modulated by local network activity. J Neurosci 31:7715-7728.
Reddy, D.S., and Rogawski, M.A. (2002). Stress-induced deoxycorticosterone-derived neurosteroids modulate GABA(A) receptor function and seizure susceptibility. The Journal of neuroscience : the official journal of the Society for Neuroscience 22, 3795-3805.
Reid CA, Dixon DB, Takahashi M, Bliss TV, Fine A (2004) Optical quantal analysis indicates that long-term potentiation at single hippocampal mossy fiber synapses is expressed through increased release probability, recruitment of new release sites, and activation of silent synapses. J Neurosci 24:3618-3626.
Rodenas-Ruano A, Chávez AE, Cossio MJ, Castillo PE, Zukin RS (2012) REST-dependent epigenetic remodeling promotes the developmental switch in synaptic NMDA receptors. Nat Neurosci 15:1382-1390.
Roozendaal B, McEwen BS, Chattarji S (2009) Stress, memory and the amygdala. Nat Rev Neurosci 10:423-433.
Rumbaugh G, Vicini S (1999) Distinct synaptic and extrasynaptic NMDA receptors in developing cerebellar granule neurons. J Neurosci 19:10603-10610.
Saal D, Dong Y, Bonci A, Malenka RC (2003) Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons. Neuron 37:577-582.
Salin PA, Scanziani M, Malenka RC, Nicoll RA (1996) Distinct short-term plasticity at two excitatory synapses in the hippocampus. Proc Natl Acad Sci USA 93:13304-13309.
Schmidt-Hieber C, Jonas P, Bischofberger J (2004) Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature 429:184-187.
Schoenfeld TJ, Gould E (2012) New neurons retire early. Nat Neurosci 15:1611-1612.
Seligman ME, Maier SF (1967) Failure to escape traumatic shock. J Exp Psychol 74:1-9.
Shen CP, Tsimberg Y, Salvadore C, Meller E (2004) Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions. BMC Neurosci 5:36.
Shors TJ, Dryver E (1994) Effect of stress and long-term potentiation (LTP) on subsequent LTP and the theta burst response in the dentate gyrus. Brain Res 666:232-238.
Shors TJ, Foy MR, Levine S, Thompson RF (1989) Unpredictable and uncontrollable stress impairs neuronal plasticity in the rat hippocampus. Brain Res Bull 24:663-667.
Simon M, Czéh B, Fuchs E (2005) Age-dependent susceptibility of adult hippocampal cell proliferation to chronic psychosocial stress. Brain Res 1049:244-248.
Snyder JS, Kee N, Wojtowicz JM (2001) Effects of adult neurogenesis on synaptic plasticity in the rat dentate gyrus. J Neurophysiol 85:2423-2431.
Soubrie, P., Thiebot, M.H., Jobert, A., Montastruc, J.L., Hery, F., and Hamon, M. (1980). Decreased convulsant potency of picrotoxin and pentetrazol and enhanced [3H]flunitrazepam cortical binding following stressful manipulations in rats. Brain research 189, 505-517.
Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85:367-370.
Südhof TC (2004) The synaptic vesicle cycle. Annu Rev Neurosci 27:509-547.
Tanapat P, Hastings NB, Rydel TA, Galea LA, Gould E (2001) Exposure to fox odor inhibits cell proliferation in the hippocampus of adult rats via an adrenal hormone-dependent mechanism. J Comp Neurol 437:496-504.
Tauber, S.C., Schlumbohm, C., Schilg, L., Fuchs, E., Nau, R., and Gerber, J. (2006). Intrauterine exposure to dexamethasone impairs proliferation but not neuronal differentiation in the dentate gyrus of newborn common marmoset monkeys. Brain Pathol 16, 209-217.
Tzounopoulos T, Janz R, Südhof TC, Nicoll RA, Malenka RC (1998) A role for cAMP in long-term depression at hippocampal mossy fiber synapses. Neuron 21:837-845.
Van Bokhoven P, Oomen CA, Hoogendijk WJ, Smit AB, Lucassen PJ, Spijker S (2011) Reduction in hippocampal neurogenesis after social defeat is long-lasting and responsive to late antidepressant treatment. Eur J Neurosci 33:1833-1840.
Vialou V, Maze I, Renthal W, LaPlant QC, Watts EL, Mouzon E, Ghose S, Tamminga CA, Nestler EJ (2010) FosB in brain reward circuits mediates resilience to stress and antidepressant responses. Nat Neurosci 13:745-752.
Wang JW, David DJ, Monckton JE, Battaglia F, Hen R (2008) Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J Neurosci 28:1374-1384.
Weisskopf MG, Castillo PE, Zalutsky RA, Nicoll RA (1994) Mediation of hippocampal mossy fiber long-term potentiation by cyclic AMP. Science 265:1878-1882.
Weisskopf MG, Nicoll RA (1995) Presynaptic changes during mossy fibre LTP revealed by NMDA receptor-mediated synaptic responses. Nature 376:256-259.
West MJ, Slomianka L, Gundersen HJ (1991) Unbiased stereological estimation of the total number of neurons in thesubdivisions of the rat hippocampus using the optical fractionator. Anat Rec 231:482-497.
Wong EY, Herbert J (2006) Raised circulating corticosterone inhibits neuronal differentiation of progenitor cells in the adult hippocampus. Neuroscience 137:83-92.
Wu ZL, Thomas SA, Villacres EC, Xia Z, Simmons ML, Chavkin C, Palmiter RD, Storm DR (1995) Altered behavior and long-term potentiation in type I adenylyl cyclase mutant mice. Proc Natl Acad Sci USA 92:220-224.
Xu L, Anwyl R, Rowan MJ (1997) Behavioural stress facilitates the induction of long-term depression in the hippocampus. Nature 387:497-500.
Yang CH, Huang CC, Hsu KS (2004) Behavioral stress modifies hippocampal synaptic plasticity through corticosterone-induced sustained extracellular signal-regulated kinase/mitogen-activated protein kinase activation. J Neurosci 24:11029-11034.
Yang CH, Huang CC, Hsu KS (2005) Behavioral stress enhances hippocampal CA1 long-term depression through the blockade of the glutamate uptake. J Neurosci 25:4288-4293.
Yang CH, Huang CC, Hsu KS (2006) Novelty exploration elicits a reversal of acute stress-induced modulation of hippocampal synaptic plasticity in the rat. J Physiol 577:601-615.
Yang PC, Yang CH, Huang CC, Hsu KS (2008) Phosphatidylinositol 3-kinase activation is required for stress protocol-induced modification of hippocampal synaptic plasticity. J Biol Chem 283:2631-2643.
Yap JJ, Takase LF, Kochman LJ, Fornal CA, Miczek KA, Jacobs BL (2006) Repeated brief social defeat episodes in mice: effects on cell proliferation in the dentate gyrus. Behav Brain Res 172:344-350.
Zalutsky RA, Nicoll RA (1990) Comparison of two forms of long-term potentiation in single hippocampal neurons. Science 248:1619-1624.
Zhao C, Teng EM, Summers RG Jr, Ming GL, Gage FH (2006) Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J Neurosci 26:3-11.
Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132:645-660.
Zucker RS (1989) Short-term synaptic plasticity. Annu Rev Neurosci 12:13-31.
Zucker RS, Regehr WG (2002) Short-term synaptic plasticity. Annu Rev Physiol 64:355-405.
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