A Simple Role for BDNF in Learning and Memory?

Since its discovery almost three decades ago, the secreted neurotrophin brain-derived neurotrophic factor (BDNF) has been firmly implicated in the differentiation and survival of neurons of the CNS. More recently, BDNF has also emerged as an important regulator of synaptogenesis and synaptic plasticity mechanisms underlying learning and memory in the adult CNS. In this review we will discuss our knowledge about the multiple intracellular signalling pathways activated by BDNF, and the role of this neurotrophin in long-term synaptic plasticity and memory formation as well as in synaptogenesis. We will show that maturation of BDNF, its cellular localization and its ability to regulate both excitatory and inhibitory synapses in the CNS may result in conflicting alterations in synaptic plasticity and memory formation. Lack of a precise knowledge about the mechanisms by which BDNF influences higher cognitive functions and complex behaviours may constitute a severe limitation in the possibility to devise BDNF-based therapeutics for human disorders of the CNS.

[1]  I. Izquierdo,et al.  BDNF Activates mTOR to Regulate GluR1 Expression Required for Memory Formation , 2009, PloS one.

[2]  K. Rosenblum,et al.  Biphasic Activation of the mTOR Pathway in the Gustatory Cortex Is Correlated with and Necessary for Taste Learning , 2009, The Journal of Neuroscience.

[3]  N. Berardi,et al.  Brain-derived neurotrophic factor (BDNF) overexpression in the forebrain results in learning and memory impairments , 2009, Neurobiology of Disease.

[4]  J. Keifer,et al.  BDNF-induced synaptic delivery of AMPAR subunits is differentially dependent on NMDA receptors and requires ERK , 2009, Neurobiology of Learning and Memory.

[5]  T. Wen,et al.  Combined treatment of neurotrophin-3 gene and neural stem cells is ameliorative to behavior recovery of Parkinson's disease rat model , 2009, Brain Research.

[6]  C. Callaghan,et al.  Deficits in LTP and recognition memory in the genetically hypertensive rat are associated with decreased expression of neurotrophic factors and their receptors in the dentate gyrus , 2009, Behavioural Brain Research.

[7]  C. Siao,et al.  Neuronal release of proBDNF , 2009, Nature Neuroscience.

[8]  P. Worley,et al.  The Immediate Early Gene Arc/Arg3.1: Regulation, Mechanisms, and Function , 2008, The Journal of Neuroscience.

[9]  Jonathan L. C. Lee,et al.  Memory reconsolidation mediates the strengthening of memories by additional learning , 2008, Nature Neuroscience.

[10]  J. Sweatt,et al.  Epigenetic Regulation of bdnf Gene Transcription in the Consolidation of Fear Memory , 2008, The Journal of Neuroscience.

[11]  K. Thomas,et al.  Proteolysis of proBDNF Is a Key Regulator in the Formation of Memory , 2008, PloS one.

[12]  J. Keifer,et al.  Coordinate action of pre- and postsynaptic brain-derived neurotrophic factor is required for AMPAR trafficking and acquisition of in vitro classical conditioning , 2008, Neuroscience.

[13]  E. Tongiorgi.  Activity-dependent expression of brain-derived neurotrophic factor in dendrites: Facts and open questions , 2008, Neuroscience Research.

[14]  C. Powell,et al.  Systemic inhibition of mammalian target of rapamycin inhibits fear memory reconsolidation , 2008, Neurobiology of Learning and Memory.

[15]  W. Abraham.  Metaplasticity: tuning synapses and networks for plasticity , 2008, Nature Reviews Neuroscience.

[16]  Martín Cammarota,et al.  On the participation of mTOR in recognition memory , 2008, Neurobiology of Learning and Memory.

[17]  I. Izquierdo,et al.  BDNF is essential to promote persistence of long-term memory storage , 2008, Proceedings of the National Academy of Sciences.

[18]  Yanling Zhao,et al.  Impaired hippocampal neurogenesis is involved in cognitive dysfunction induced by thiamine deficiency at early pre-pathological lesion stage , 2008, Neurobiology of Disease.

[19]  E. Kandel,et al.  Gene Expression Profiling of Facilitated L-LTP in VP16-CREB Mice Reveals that BDNF Is Critical for the Maintenance of LTP and Its Synaptic Capture , 2007, Neuron.

[20]  Roberto Malinow,et al.  Emotion Enhances Learning via Norepinephrine Regulation of AMPA-Receptor Trafficking , 2007, Cell.

[21]  C. Bramham,et al.  Dendritic mRNA: transport, translation and function , 2007, Nature Reviews Neuroscience.

[22]  P. Gean,et al.  Transcriptional Regulation of Brain-Derived Neurotrophic Factor in the Amygdala during Consolidation of Fear Memory , 2007, Molecular Pharmacology.

[23]  David Dupret,et al.  Spatial Learning Depends on Both the Addition and Removal of New Hippocampal Neurons , 2007, PLoS biology.

[24]  Danielle A. Simmons,et al.  Evidence That Long-Term Potentiation Occurs within Individual Hippocampal Synapses during Learning , 2007, The Journal of Neuroscience.

[25]  G. Turrigiano.  Homeostatic signaling: the positive side of negative feedback , 2007, Current Opinion in Neurobiology.

[26]  S. Hughes,et al.  AAV‐mediated delivery of BDNF augments neurogenesis in the normal and quinolinic acid‐lesioned adult rat brain , 2007, The European journal of neuroscience.

[27]  K. Young,et al.  p75 Neurotrophin Receptor Expression Defines a Population of BDNF-Responsive Neurogenic Precursor Cells , 2007, The Journal of Neuroscience.

[28]  M. Amaral,et al.  TRPC3 Channels Are Necessary for Brain-Derived Neurotrophic Factor to Activate a Nonselective Cationic Current and to Induce Dendritic Spine Formation , 2007, The Journal of Neuroscience.

[29]  J. Sweatt,et al.  Covalent Modification of DNA Regulates Memory Formation , 2007, Neuron.

[30]  G. Lynch,et al.  Brain-Derived Neurotrophic Factor Promotes Long-Term Potentiation-Related Cytoskeletal Changes in Adult Hippocampus , 2007, The Journal of Neuroscience.

[31]  Afra H. Wang,et al.  Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus , 2007, Nature Neuroscience.

[32]  Lu Chen,et al.  Dynamics of postsynaptic glutamate receptor targeting , 2007, Current Opinion in Neurobiology.

[33]  I. Izquierdo,et al.  mTOR signaling in the hippocampus is necessary for memory formation , 2007, Neurobiology of Learning and Memory.

[34]  K. Ressler,et al.  Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories , 2007, Molecular Psychiatry.

[35]  I. Izquierdo,et al.  Persistence of Long-Term Memory Storage Requires a Late Protein Synthesis- and BDNF- Dependent Phase in the Hippocampus , 2007, Neuron.

[36]  Kaia Palm,et al.  Mouse and rat BDNF gene structure and expression revisited , 2006, Journal of neuroscience research.

[37]  Debabrata Panja,et al.  Dual regulation of translation initiation and peptide chain elongation during BDNF‐induced LTP in vivo: evidence for compartment‐specific translation control , 2006, Journal of neurochemistry.

[38]  C. Bramham,et al.  Brain-derived neurotrophic factor and control of synaptic consolidation in the adult brain. , 2006, Biochemical Society transactions.

[39]  Michael Davis,et al.  Amygdala BDNF signaling is required for consolidation but not encoding of extinction , 2006, Nature Neuroscience.

[40]  T. Bonhoeffer,et al.  Hippocampal Long-Term Potentiation Is Supported by Presynaptic and Postsynaptic Tyrosine Receptor Kinase B-Mediated Phospholipase Cγ Signaling , 2006, The Journal of Neuroscience.

[41]  Lin Lu,et al.  Rodent BDNF genes, novel promoters, novel splice variants, and regulation by cocaine , 2006, Brain Research.

[42]  T. Bonhoeffer,et al.  The p75 Neurotrophin Receptor Negatively Modulates Dendrite Complexity and Spine Density in Hippocampal Neurons , 2005, The Journal of Neuroscience.

[43]  A. Nikolakopoulou,et al.  BDNF stabilizes synapses and maintains the structural complexity of optic axons in vivo , 2005, Development.

[44]  I. Izquierdo,et al.  Endogenous BDNF is required for long-term memory formation in the rat parietal cortex. , 2005, Learning & memory.

[45]  Petti T. Pang,et al.  The yin and yang of neurotrophin action , 2005, Nature Reviews Neuroscience.

[46]  Bai Lu,et al.  Activation of p75NTR by proBDNF facilitates hippocampal long-term depression , 2005, Nature Neuroscience.

[47]  Barbara L. Hempstead,et al.  ProBDNF Induces Neuronal Apoptosis via Activation of a Receptor Complex of p75NTR and Sortilin , 2005, The Journal of Neuroscience.

[48]  C. Bramham,et al.  BDNF function in adult synaptic plasticity: The synaptic consolidation hypothesis , 2005, Progress in Neurobiology.

[49]  M. Boccia,et al.  NF‐κB transcription factor is required for inhibitory avoidance long‐term memory in mice , 2005, The European journal of neuroscience.

[50]  Mariza de Andrade,et al.  Human brain derived neurotrophic factor (BDNF) genes, splicing patterns, and assessments of associations with substance abuse and Parkinson's Disease , 2005, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[51]  Joseph E LeDoux,et al.  Postsynaptic Receptor Trafficking Underlying a Form of Associative Learning , 2005, Science.

[52]  H. Scharfman,et al.  Increased neurogenesis and the ectopic granule cells after intrahippocampal BDNF infusion in adult rats , 2005, Experimental Neurology.

[53]  Gary Lynch,et al.  Theta Stimulation Polymerizes Actin in Dendritic Spines of Hippocampus , 2005, The Journal of Neuroscience.

[54]  Mikko Sairanen,et al.  Brain-Derived Neurotrophic Factor and Antidepressant Drugs Have Different But Coordinated Effects on Neuronal Turnover, Proliferation, and Survival in the Adult Dentate Gyrus , 2005, The Journal of Neuroscience.

[55]  Cristina M. Alberini,et al.  Mechanisms of memory stabilization: are consolidation and reconsolidation similar or distinct processes? , 2005, Trends in Neurosciences.

[56]  E. Klann,et al.  Biochemical mechanisms for translational regulation in synaptic plasticity , 2004, Nature Reviews Neuroscience.

[57]  Spartaco Santi,et al.  Induction of long-term potentiation and depression is reflected by corresponding changes in secretion of endogenous brain-derived neurotrophic factor. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[58]  A. Konnerth,et al.  From modulator to mediator: rapid effects of BDNF on ion channels , 2004, BioEssays : news and reviews in molecular, cellular and developmental biology.

[59]  Michael Davis,et al.  Differential regulation of brain-derived neurotrophic factor transcripts during the consolidation of fear learning. , 2004, Learning & memory.

[60]  Petti T. Pang,et al.  Cleavage of proBDNF by tPA/Plasmin Is Essential for Long-Term Hippocampal Plasticity , 2004, Science.

[61]  Susumu Tonegawa,et al.  Translational Regulatory Mechanisms in Persistent Forms of Synaptic Plasticity , 2004, Neuron.

[62]  D. Molfese,et al.  Regulation of Histone Acetylation during Memory Formation in the Hippocampus* , 2004, Journal of Biological Chemistry.

[63]  Wen G. Chen,et al.  BDNF Regulates the Translation of a Select Group of mRNAs by a Mammalian Target of Rapamycin-Phosphatidylinositol 3-Kinase-Dependent Pathway during Neuronal Development , 2004, The Journal of Neuroscience.

[64]  M. Barrot,et al.  Essential role of brain-derived neurotrophic factor in adult hippocampal function. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[65]  J. Sweatt,et al.  Mitogen-activated protein kinases in synaptic plasticity and memory , 2004, Current Opinion in Neurobiology.

[66]  Michael Davis,et al.  Brain-Derived Neurotrophic Factor and Tyrosine Kinase Receptor B Involvement in Amygdala-Dependent Fear Conditioning , 2004, The Journal of Neuroscience.

[67]  B. Everitt,et al.  Independent Cellular Processes for Hippocampal Memory Consolidation and Reconsolidation , 2004, Science.

[68]  Paresh D Patel,et al.  Variant Brain-Derived Neurotrophic Factor (BDNF) (Met66) Alters the Intracellular Trafficking and Activity-Dependent Secretion of Wild-Type BDNF in Neurosecretory Cells and Cortical Neurons , 2004, The Journal of Neuroscience.

[69]  Rémi Quirion,et al.  Comparative signaling pathways of insulin‐like growth factor‐1 and brain‐derived neurotrophic factor in hippocampal neurons and the role of the PI3 kinase pathway in cell survival , 2004, Journal of neurochemistry.

[70]  E. Castrén,et al.  Transgenic mice overexpressing the full-length neurotrophin receptor trkB exhibit increased activation of the trkB–PLCγ pathway, reduced anxiety, and facilitated learning , 2004, Molecular and Cellular Neuroscience.

[71]  J. Medina,et al.  ERK1/2 activation is necessary for BDNF to increase dendritic spine density in hippocampal CA1 pyramidal neurons. , 2004, Learning & memory.

[72]  R. Huganir,et al.  MAPK cascade signalling and synaptic plasticity , 2004, Nature Reviews Neuroscience.

[73]  Y. Shaham,et al.  A Single Infusion of Brain-Derived Neurotrophic Factor into the Ventral Tegmental Area Induces Long-Lasting Potentiation of Cocaine Seeking after Withdrawal , 2004, The Journal of Neuroscience.

[74]  S. Kish,et al.  Brain dopamine‐stimulated adenylyl cyclase activity in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy , 2004, Annals of neurology.

[75]  R. Segal,et al.  Selectivity in neurotrophin signaling: theme and variations. , 2003, Annual review of neuroscience.

[76]  E. Huang,et al.  Trk receptors: roles in neuronal signal transduction. , 2003, Annual review of biochemistry.

[77]  T. Tsumoto,et al.  Brain-derived neurotrophic factor-dependent unmasking of “silent” synapses in the developing mouse barrel cortex , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[78]  K. Nader.  Neuroscience: Re-recording human memories , 2003, Nature.

[79]  J. Gorski,et al.  Learning deficits in forebrain-restricted brain-derived neurotrophic factor mutant mice , 2003, Neuroscience.

[80]  Kristen M Harris,et al.  Structural changes at dendritic spine synapses during long-term potentiation. , 2003, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[81]  Volkmar Lessmann,et al.  Neurotrophin secretion: current facts and future prospects , 2003, Progress in Neurobiology.

[82]  M. Chao,et al.  Neurotrophins and their receptors: A convergence point for many signalling pathways , 2003, Nature Reviews Neuroscience.

[83]  E. Kandel,et al.  CREB, memory enhancement and the treatment of memory disorders: promises, pitfalls and prospects , 2003, Expert opinion on therapeutic targets.

[84]  M. Egan,et al.  The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal Function , 2003, Cell.

[85]  Tracey J. Shors,et al.  Associative Memory Formation Increases the Observation of Dendritic Spines in the Hippocampus , 2003, The Journal of Neuroscience.

[86]  I. Izquierdo,et al.  Signaling Mechanisms Mediating BDNF Modulation of Memory Formation In Vivo in the Hippocampus , 2002, Cellular and Molecular Neurobiology.

[87]  Eric C. Griffith,et al.  Regulation of transcription factors by neuronal activity , 2002, Nature Reviews Neuroscience.

[88]  L. Maffei,et al.  Heterozygous Knock-Out Mice for Brain-Derived Neurotrophic Factor Show a Pathway-Specific Impairment of Long-Term Potentiation But Normal Critical Period for Monocular Deprivation , 2002, The Journal of Neuroscience.

[89]  D. Katz,et al.  Cellular Mechanisms Regulating Activity-Dependent Release of Native Brain-Derived Neurotrophic Factor from Hippocampal Neurons , 2002, The Journal of Neuroscience.

[90]  P. Gean,et al.  A Requirement of Nuclear Factor-κB Activation in Fear-potentiated Startle* , 2002, The Journal of Biological Chemistry.

[91]  E. Castrén,et al.  Regulation of TRKB Surface Expression by Brain-derived Neurotrophic Factor and Truncated TRKB Isoforms* , 2002, The Journal of Biological Chemistry.

[92]  K. Araki,et al.  Brain-derived Neurotrophic Factor Regulates Surface Expression of α-Amino-3-hydroxy-5-methyl-4-isoxazoleproprionic Acid Receptors by Enhancing the N-Ethylmaleimide-sensitive Factor/GluR2 Interaction in Developing Neocortical Neurons* , 2002, The Journal of Biological Chemistry.

[93]  A. Konnerth,et al.  Neurotrophin-evoked depolarization requires the sodium channel NaV1.9 , 2002, Nature.

[94]  E. Shooter,et al.  BDNF overexpression increases dendrite complexity in hippocampal dentate gyrus , 2002, Neuroscience.

[95]  T. Bonhoeffer,et al.  Mechanism of TrkB-Mediated Hippocampal Long-Term Potentiation , 2002, Neuron.

[96]  D. Ippolito,et al.  N-terminal Tyrosine Residues within the Potassium Channel Kir3 Modulate GTPase Activity of Gαi * , 2002, The Journal of Biological Chemistry.

[97]  C. Bramham,et al.  Brain-Derived Neurotrophic Factor Triggers Transcription-Dependent, Late Phase Long-Term Potentiation In Vivo , 2002, The Journal of Neuroscience.

[98]  Glenn C. Turner,et al.  Oscillations and Sparsening of Odor Representations in the Mushroom Body , 2002, Science.

[99]  K. Tucker,et al.  Neurotrophin modulation of voltage‐gated potassium channels in rat through TrkB receptors is time and sensory experience dependent , 2002, The Journal of physiology.

[100]  T. Bliss,et al.  Brain-Derived Neurotrophic Factor Induces Long-Term Potentiation in Intact Adult Hippocampus: Requirement for ERK Activation Coupled to CREB and Upregulation of Arc Synthesis , 2002, The Journal of Neuroscience.

[101]  G. Edelman,et al.  The brain-derived neurotrophic factor enhances synthesis of Arc in synaptoneurosomes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[102]  R. Heumann,et al.  Synaptic secretion of BDNF after high‐frequency stimulation of glutamatergic synapses , 2001, The EMBO journal.

[103]  E. Kandel,et al.  Some Forms of cAMP-Mediated Long-Lasting Potentiation Are Associated with Release of BDNF and Nuclear Translocation of Phospho-MAP Kinase , 2001, Neuron.

[104]  P. Gean,et al.  A Role for the PI-3 Kinase Signaling Pathway in Fear Conditioning and Synaptic Plasticity in the Amygdala , 2001, Neuron.

[105]  Theresa M. Desrochers,et al.  Two different lateral amygdala cell populations contribute to the initiation and storage of memory , 2001, Nature Neuroscience.

[106]  W. Tyler,et al.  BDNF Enhances Quantal Neurotransmitter Release and Increases the Number of Docked Vesicles at the Active Zones of Hippocampal Excitatory Synapses , 2001, The Journal of Neuroscience.

[107]  Erin M. Schuman,et al.  Dynamic Visualization of Local Protein Synthesis in Hippocampal Neurons , 2001, Neuron.

[108]  N. Seidah,et al.  Biosynthesis and Post-translational Processing of the Precursor to Brain-derived Neurotrophic Factor* , 2001, The Journal of Biological Chemistry.

[109]  M. Murer,et al.  Brain-derived neurotrophic factor in the control human brain, and in Alzheimer’s disease and Parkinson’s disease , 2001, Progress in Neurobiology.

[110]  E. Castrén,et al.  Transgenic mice overexpressing truncated trkB neurotrophin receptors in neurons have impaired long‐term spatial memory but normal hippocampal LTP , 2000, Synapse.

[111]  Kiyofumi Yamada,et al.  Involvement of Brain-Derived Neurotrophic Factor in Spatial Memory Formation and Maintenance in a Radial Arm Maze Test in Rats , 2000, The Journal of Neuroscience.

[112]  T. Tsumoto,et al.  Actions of brain‐derived neurotrophic factor on evoked and spontaneous EPSCs dissociate with maturation of neurones cultured from rat visual cortex , 2000, The Journal of physiology.

[113]  David R Kaplan,et al.  Neurotrophin signal transduction in the nervous system , 2000, Current Opinion in Neurobiology.

[114]  Barry J. Everitt,et al.  Rapid and selective induction of BDNF expression in the hippocampus during contextual learning , 2000, Nature Neuroscience.

[115]  P. Greengard,et al.  Synapsins as mediators of BDNF-enhanced neurotransmitter release , 2000, Nature Neuroscience.

[116]  C. Wihler,et al.  Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[117]  Bruce L. McNaughton,et al.  Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles , 1999, Nature Neuroscience.

[118]  N. Toni,et al.  LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite , 1999, Nature.

[119]  A. Konnerth,et al.  Neurotrophin-evoked rapid excitation through TrkB receptors , 1999, Nature.

[120]  Tobias Bonhoeffer,et al.  Essential Role for TrkB Receptors in Hippocampus-Mediated Learning , 1999, Neuron.

[121]  L. Maffei,et al.  BDNF Regulates the Maturation of Inhibition and the Critical Period of Plasticity in Mouse Visual Cortex , 1999, Cell.

[122]  C. Montell,et al.  Activation of a TRPC3-Dependent Cation Current through the Neurotrophin BDNF , 1999, Neuron.

[123]  H. Scharfman,et al.  Brain-derived neurotrophic factor transgenic mice exhibit passive avoidance deficits, increased seizure severity and in vitro hyperexcitability in the hippocampus and entorhinal cortex , 1999, Neuroscience.

[124]  Z. Yao,et al.  Deprivation of endogenous brain-derived neurotrophic factor results in impairment of spatial learning and memory in adult rats , 1999, Brain Research.

[125]  L. Zhang,et al.  Impairments in High-Frequency Transmission, Synaptic Vesicle Docking, and Synaptic Protein Distribution in the Hippocampus of BDNF Knockout Mice , 1999, The Journal of Neuroscience.

[126]  H. Thoenen,et al.  Are there differences between the secretion characteristics of NGF and BDNF? Implications for the modulatory role of neurotrophins in activity‐dependent neuronal plasticity , 1999, Microscopy research and technique.

[127]  F. Engert,et al.  Dendritic spine changes associated with hippocampal long-term synaptic plasticity , 1999, Nature.

[128]  Niraj S. Desai,et al.  BDNF regulates the intrinsic excitability of cortical neurons. , 1999, Learning & memory.

[129]  K. Svoboda,et al.  Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. , 1999, Science.

[130]  E. Quinlan,et al.  CPEB-Mediated Cytoplasmic Polyadenylation and the Regulation of Experience-Dependent Translation of α-CaMKII mRNA at Synapses , 1998, Neuron.

[131]  C. Cotman,et al.  Learning upregulates brain-derived neurotrophic factor messenger ribonucleic acid: a mechanism to facilitate encoding and circuit maintenance? , 1998, Behavioral neuroscience.

[132]  M. Frotscher,et al.  Hippocampal mossy fiber sprouting is not impaired in brain-derived neurotrophic factor-deficient mice , 1998, Experimental Brain Research.

[133]  Hyejin Kang,et al.  A role for BDNF in the late-phase of hippocampal long-term potentiation , 1998, Neuropharmacology.

[134]  E. Tongiorgi,et al.  Activity-Dependent Dendritic Targeting of BDNF and TrkB mRNAs in Hippocampal Neurons , 1997, The Journal of Neuroscience.

[135]  S. Linnarsson,et al.  Learning Deficit in BDNF Mutant Mice , 1997, The European journal of neuroscience.

[136]  T. Ikeuchi,et al.  Insulin Receptor Substrate (IRS)-1 and IRS-2 Are Tyrosine-phosphorylated and Associated with Phosphatidylinositol 3-Kinase in Response to Brain-derived Neurotrophic Factor in Cultured Cerebral Cortical Neurons* , 1997, The Journal of Biological Chemistry.

[137]  H. Thoenen,et al.  Neurotrophin release by neurotrophins: implications for activity-dependent neuronal plasticity. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[138]  Y. L. Ma,et al.  Brain-derived neurotrophic factor antisense oligonucleotide impairs memory retention and inhibits long-term potentiation in rats , 1997, Neuroscience.

[139]  Steven Finkbeiner,et al.  CREB: A Major Mediator of Neuronal Neurotrophin Responses , 1997, Neuron.

[140]  E. Schuman,et al.  Neurotrophins and Time: Different Roles for TrkB Signaling in Hippocampal Long-Term Potentiation , 1997, Neuron.

[141]  T. Tsumoto,et al.  Brain-Derived Neurotrophic Factor Enhances Long-Term Potentiation in Rat Visual Cortex , 1997, The Journal of Neuroscience.

[142]  G G Turrigiano,et al.  Brain-Derived Neurotrophic Factor Mediates the Activity-Dependent Regulation of Inhibition in Neocortical Cultures , 1997, The Journal of Neuroscience.

[143]  M. Barbacid,et al.  TrkB Signaling Is Required for Postnatal Survival of CNS Neurons and Protects Hippocampal and Motor Neurons from Axotomy-Induced Cell Death , 1997, The Journal of Neuroscience.

[144]  Lawrence C. Katz,et al.  Opposing Roles for Endogenous BDNF and NT-3 in Regulating Cortical Dendritic Growth , 1997, Neuron.

[145]  R. Klein,et al.  TrkB and TrkC neurotrophin receptors cooperate in promoting survival of hippocampal and cerebellar granule neurons. , 1996, Genes & development.

[146]  J. Kimura,et al.  Immunohistochemical localization of brain-derived neurotrophic factor in adult rat brain , 1996, Neuroscience.

[147]  B. Lu,et al.  Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus , 1996, Nature.

[148]  Ted Abel,et al.  Recombinant BDNF Rescues Deficits in Basal Synaptic Transmission and Hippocampal LTP in BDNF Knockout Mice , 1996, Neuron.

[149]  A. Konnerth,et al.  Long-term potentiation and functional synapse induction in developing hippocampus , 1996, Nature.

[150]  N. Seidah,et al.  Cellular processing of the neurotrophin precursors of NT3 and BDNF by the mammalian proprotein convertases , 1996, FEBS letters.

[151]  C. Altar,et al.  Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[152]  Lawrence C. Katz,et al.  Neurotrophins regulate dendritic growth in developing visual cortex , 1995, Neuron.

[153]  T Bonhoeffer,et al.  Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[154]  F. Hefti,et al.  Immunohistochemical Visualization of Brain‐derived Neurotrophic Factor in the Rat Brain , 1995, The European journal of neuroscience.

[155]  J. Isaac,et al.  Evidence for silent synapses: Implications for the expression of LTP , 1995, Neuron.

[156]  R. Malinow,et al.  Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice , 1995, Nature.

[157]  E. Schuman,et al.  Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus , 1995, Science.

[158]  I. Fariñas,et al.  Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development , 1994, Cell.

[159]  M E Greenberg,et al.  Requirement for BDNF in activity-dependent survival of cortical neurons. , 1994, Science.

[160]  Rudolf Jaenisch,et al.  Mice lacking brain-derived neurotrophic factor develop with sensory deficits , 1994, Nature.

[161]  M. Barbacid,et al.  Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death , 1993, Cell.

[162]  P. Gluckman,et al.  Brain-derived neurotrophic factor expression after long-term potentiation , 1993, Neuroscience Letters.

[163]  F. Morrell,et al.  Structural synaptic correlate of long‐term potentiation: Formation of axospinous synapses with multiple, completely partitioned transmission zones , 1993, Hippocampus.

[164]  B L McNaughton,et al.  Dynamics of the hippocampal ensemble code for space. , 1993, Science.

[165]  E. Castrén,et al.  The induction of LTP increases BDNF and NGF mRNA but decreases NT-3 mRNA in the dentate gyrus. , 1993, Neuroreport.

[166]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[167]  W B Levy,et al.  Spatial overlap between populations of synapses determines the extent of their associative interaction during the induction of long-term potentiation and depression. , 1990, Journal of neurophysiology.

[168]  M. Barbacid,et al.  The trkB tyrosine protein kinase gene codes for a second neurogenic receptor that lacks the catalytic kinase domain , 1990, Cell.

[169]  W. Greenough,et al.  Transient and enduring morphological correlates of synaptic activity and efficacy change in the rat hippocampal slice , 1984, Brain Research.

[170]  H. Thoenen,et al.  Purification of a new neurotrophic factor from mammalian brain. , 1982, The EMBO journal.

[171]  G Lynch,et al.  Brief bursts of high-frequency stimulation produce two types of structural change in rat hippocampus. , 1980, Journal of neurophysiology.

[172]  V. Hamburger,et al.  A NERVE GROWTH-STIMULATING FACTOR ISOLATED FROM SARCOM AS 37 AND 180. , 1954, Proceedings of the National Academy of Sciences of the United States of America.

[173]  J. Delgado-García,et al.  Mutation at the TrkB PLC{gamma}-docking site affects hippocampal LTP and associative learning in conscious mice. , 2007, Learning & memory.

[174]  B. Christie,et al.  Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways , 2006, Hippocampus.

[175]  H. Maldonado,et al.  Activation of the transcription factor NF-kappaB by retrieval is required for long-term memory reconsolidation. , 2005, Learning & memory.

[176]  Petti T. Pang,et al.  Activation of p 75 NTR by proBDNF facilitates hippocampal long-term depression , 2005 .

[177]  Flavia Chiarotti,et al.  Intrahippocampal administration of BDNF in adult rats affects short‐term behavioral plasticity in the Morris water maze and performance in the elevated plus‐maze , 2004, Hippocampus.

[178]  D. Fuller,et al.  BDNF is necessary and sufficient for spinal respiratory plasticity following intermittent hypoxia , 2004, Nature Neuroscience.

[179]  G. Ariav,et al.  Olfactory learning‐induced increase in spine density along the apical dendrites of CA1 hippocampal neurons , 2004, Hippocampus.

[180]  M. Bouton,et al.  Importance of trials versus accumulating time across trials in partially reinforced appetitive conditioning. , 2003, Journal of experimental psychology. Animal behavior processes.

[181]  水野 誠.  Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats , 2002 .

[182]  P. Gean,et al.  A requirement of nuclear factor-kappaB activation in fear-potentiated startle. , 2002, The Journal of biological chemistry.

[183]  Mu-ming Poo,et al.  Neurotrophins as synaptic modulators , 2001, Nature Reviews Neuroscience.

[184]  S. J. Martin,et al.  Synaptic plasticity and memory: an evaluation of the hypothesis. , 2000, Annual review of neuroscience.

[185]  Mu-ming Poo,et al.  Postsynaptic Target Specificity of Neurotrophin-Induced Presynaptic Potentiation , 2000, Neuron.

[186]  B. Lu,et al.  Role of Neurotrophins in Synapse Development and Plasticity , 1997, Reviews in the neurosciences.

[187]  C Chen,et al.  Molecular genetic analysis of synaptic plasticity, activity-dependent neural development, learning, and memory in the mammalian brain. , 1997, Annual review of neuroscience.

[188]  K. Anderson,et al.  BDNF down-regulates neurotrophin responsiveness, TrkB protein and TrkB mRNA levels in cultured rat hippocampal neurons. , 1996, The European journal of neuroscience.

[189]  L. R. Williams,et al.  Regional stimulation of cholinergic function by nerve growth factor in an animal model of Alzheimer's disease. , 1989, Progress in clinical and biological research.