From Synapse to Nucleus: Calcium-Dependent Gene Transcription in the Control of Synapse Development and Function

One of the unique characteristics of higher organisms is their ability to learn and adapt to changes in their environment. This plasticity is largely a result of the brain's ability to convert transient stimuli into long-lasting alterations in neuronal structure and function. This process is complex and involves changes in receptor trafficking, local mRNA translation, protein turnover, and new gene synthesis. Here, we review how neuronal activity triggers calcium-dependent gene expression to regulate synapse development, maturation, and refinement. Interestingly, many components of the activity-dependent gene expression program are mutated in human cognitive disorders, which suggest that this program is essential for proper brain development and function.

[1]  M. Greenberg,et al.  Stimulation of neuronal acetylcholine receptors induces rapid gene transcription. , 1986, Science.

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

[3]  M. Greenberg,et al.  A Biological Function for the Neuronal Activity-Dependent Component of Bdnf Transcription in the Development of Cortical Inhibition , 2008, Neuron.

[4]  T. Soderling,et al.  Regulatory mechanisms of AMPA receptors in synaptic plasticity , 2007, Nature Reviews Neuroscience.

[5]  Z. Mao,et al.  Calcineurin Enhances MEF2 DNA Binding Activity in Calcium-dependent Survival of Cerebellar Granule Neurons* , 1999, The Journal of Biological Chemistry.

[6]  Eric M. Morrow,et al.  Identifying Autism Loci and Genes by Tracing Recent Shared Ancestry , 2008, Science.

[7]  M. Dragunow,et al.  Kindling stimulation induces c-fos protein(s) in granule cells of the rat dentate gyrus , 1987, Nature.

[8]  M. Montminy,et al.  Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133 , 1989, Cell.

[9]  T. Soderling,et al.  Activity-Dependent Dendritic Arborization Mediated by CaM-Kinase I Activation and Enhanced CREB-Dependent Transcription of Wnt-2 , 2006, Neuron.

[10]  Gail Mandel,et al.  REST: A mammalian silencer protein that restricts sodium channel gene expression to neurons , 1995, Cell.

[11]  J. Hell,et al.  Biochemical properties and subcellular distribution of an N-type calcium hannel α1 subunit , 1992, Neuron.

[12]  M. Mattson,et al.  Roles for NF-κB in nerve cell survival, plasticity, and disease , 2006, Cell Death and Differentiation.

[13]  Hollis T. Cline,et al.  Postsynaptic CPG15 promotes synaptic maturation and presynaptic axon arbor elaboration in vivo , 2000, Nature Neuroscience.

[14]  Eric C. Griffith,et al.  Brain-Specific Phosphorylation of MeCP2 Regulates Activity-Dependent Bdnf Transcription, Dendritic Growth, and Spine Maturation , 2006, Neuron.

[15]  Hilmar Bading,et al.  Distinct functions of nuclear and cytoplasmic calcium in the control of gene expression , 1997, Nature.

[16]  Athar N. Malik,et al.  Activity-dependent regulation of inhibitory synapse development by Npas4 , 2008, Nature.

[17]  Eric R. Kandel,et al.  Injection of the cAMP-responsive element into the nucleus of Aplysia sensory neurons blocks long-term facilitation , 1990, Nature.

[18]  Loren Miraglia,et al.  TORCs: transducers of regulated CREB activity. , 2003, Molecular cell.

[19]  M. Greenberg,et al.  A growth factor-induced kinase phosphorylates the serum response factor at a site that regulates its DNA-binding activity , 1993, Molecular and cellular biology.

[20]  R. Malenka,et al.  AMPA receptor trafficking and synaptic plasticity. , 2002, Annual review of neuroscience.

[21]  Joshua M. Stuart,et al.  Molecular Network and Chromosomal Clustering of Genes Involved in Synaptic Plasticity in the Hippocampus* , 2006, Journal of Biological Chemistry.

[22]  D. Warner.  Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways. , 1993 .

[23]  D. Ginty,et al.  Calcium Regulation of Gene Expression: Isn't That Spatial? , 1997, Neuron.

[24]  H. Youn,et al.  Cabin1 represses MEF2-dependent Nur77 expression and T cell apoptosis by controlling association of histone deacetylases and acetylases with MEF2. , 2000, Immunity.

[25]  A. Nordheim,et al.  The ability of a ternary complex to form over the serum response element correlates with serum inducibility of the human c-fos promoter , 1989, Cell.

[26]  Raoul C. M. Hennekam,et al.  Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP , 1995, Nature.

[27]  H. Cline,et al.  Synaptogenesis: A Balancing Act between Excitation and Inhibition , 2005, Current Biology.

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

[29]  M. Gratacós,et al.  Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type , 2003, Molecular Psychiatry.

[30]  M. Mattson,et al.  Roles for NF-kappaB in nerve cell survival, plasticity, and disease. , 2006, Cell death and differentiation.

[31]  A. Bird,et al.  DNA methylation specifies chromosomal localization of MeCP2 , 1996, Molecular and cellular biology.

[32]  Eric C. Griffith,et al.  Derepression of BDNF Transcription Involves Calcium-Dependent Phosphorylation of MeCP2 , 2003, Science.

[33]  E. Kandel,et al.  Activation of cAMP-Responsive genes by stimuli that produce long-term facilitation in aplysia sensory neurons , 1993, Neuron.

[34]  M.,et al.  L-type VoltageSensitive Calcium Channels Mediate Synaptic Activation of Immediate Early , 2003 .

[35]  J. Hell,et al.  Biochemical properties and subcellular distribution of an N-type calcium channel alpha 1 subunit. , 1992, Neuron.

[36]  W. Sather,et al.  AKAP79/150 Anchoring of Calcineurin Controls Neuronal L-Type Ca2+ Channel Activity and Nuclear Signaling , 2007, Neuron.

[37]  Alcino J. Silva,et al.  Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein , 1994, Cell.

[38]  Michael R. Green,et al.  Nuclear protein CBP is a coactivator for the transcription factor CREB , 1994, Nature.

[39]  Kenji Yamamoto,et al.  Inhibition of Dendritic Spine Morphogenesis and Synaptic Transmission by Activity-Inducible Protein Homer1a , 2003, The Journal of Neuroscience.

[40]  D. Hubel,et al.  EFFECTS OF VISUAL DEPRIVATION ON MORPHOLOGY AND PHYSIOLOGY OF CELLS IN THE CATS LATERAL GENICULATE BODY. , 1963, Journal of neurophysiology.

[41]  A. Orth,et al.  Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[42]  C. Shatz,et al.  Synaptic Activity and the Construction of Cortical Circuits , 1996, Science.

[43]  Britt Mellström,et al.  DREAM is a Ca2+-regulated transcriptional repressor , 1999, Nature.

[44]  S. Priori,et al.  CaV1.2 Calcium Channel Dysfunction Causes a Multisystem Disorder Including Arrhythmia and Autism , 2004, Cell.

[45]  Stephen T. C. Wong,et al.  MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription , 2008, Science.

[46]  M. Egan,et al.  Brain-Derived Neurotrophic Factor val66met Polymorphism Affects Human Memory-Related Hippocampal Activity and Predicts Memory Performance , 2003, The Journal of Neuroscience.

[47]  M. Sheng,et al.  Regulation of NMDA receptors by an associated phosphatase-kinase signaling complex. , 1999, Science.

[48]  E. Kandel.  The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses , 2001, Science.

[49]  Steven W. Flavell,et al.  Activity-Dependent Regulation of MEF2 Transcription Factors Suppresses Excitatory Synapse Number , 2006, Science.

[50]  N. Woo,et al.  Distinct Role of Long 3′ UTR BDNF mRNA in Spine Morphology and Synaptic Plasticity in Hippocampal Neurons , 2008, Cell.

[51]  G. Quirk,et al.  Neuronal signalling of fear memory , 2004, Nature Reviews Neuroscience.

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

[53]  D J Anderson,et al.  The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes , 1995, Science.

[54]  William A. Catterall,et al.  Clustering of L-type Ca2+ channels at the base of major dendrites in hippocampal pyramidal neurons , 1990, Nature.

[55]  Eric R. Kandel,et al.  Expression of Constitutively Active CREB Protein Facilitates the Late Phase of Long-Term Potentiation by Enhancing Synaptic Capture , 2002, Cell.

[56]  T. Wiesel.  Postnatal development of the visual cortex and the influence of environment , 1982, Nature.

[57]  J. Lichtman,et al.  Alterations in Synaptic Strength Preceding Axon Withdrawal , 1997, Science.

[58]  T. Serwold,et al.  Dendrite growth increased by visual activity requires NMDA receptor and Rho GTPases , 2022 .

[59]  Kendra K Bence-Hanulec,et al.  Potentiation of Neuronal L Calcium Channels by IGF-1 Requires Phosphorylation of the α1 Subunit on a Specific Tyrosine Residue , 2000, Neuron.

[60]  M E Greenberg,et al.  Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways. , 1993, Science.

[61]  U. Schibler,et al.  Phosphorylation of CREB Ser142 Regulates Light-Induced Phase Shifts of the Circadian Clock , 2002, Neuron.

[62]  Azad Bonni,et al.  A CaMKII-NeuroD Signaling Pathway Specifies Dendritic Morphogenesis , 2004, Neuron.

[63]  S. Hyman,et al.  Regulation of immediate early gene expression and AP-1 binding in the rat nucleus accumbens by chronic cocaine. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[64]  Wen G. Chen,et al.  Upstream Stimulatory Factors Are Mediators of Ca2+-Responsive Transcription in Neurons , 2003, The Journal of Neuroscience.

[65]  T. Soderling,et al.  Activity-Dependent Synaptogenesis: Regulation by a CaM-Kinase Kinase/CaM-Kinase I/βPIX Signaling Complex , 2008, Neuron.

[66]  Junmin Peng,et al.  Cdk5-Mediated Inhibition of the Protective Effects of Transcription Factor MEF2 in Neurotoxicity-Induced Apoptosis , 2003, Neuron.

[67]  Rudolf Jaenisch,et al.  Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett syndrome. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[68]  P. Jonas,et al.  Molecular mechanisms controlling calcium entry through AMPA-type glutamate receptor channels , 1995, Neuron.

[69]  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.

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

[71]  Bryan M. Hooks,et al.  Critical Periods in the Visual System: Changing Views for a Model of Experience-Dependent Plasticity , 2007, Neuron.

[72]  A. Rao,et al.  The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation , 2007, Nature.

[73]  Daisuke Hattori,et al.  DNA Methylation-Related Chromatin Remodeling in Activity-Dependent Bdnf Gene Regulation , 2003, Science.

[74]  Mi-Sung Kim,et al.  MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function , 2008, Proceedings of the National Academy of Sciences.

[75]  Richard L. Huganir,et al.  Arc/Arg3.1 Interacts with the Endocytic Machinery to Regulate AMPA Receptor Trafficking , 2006, Neuron.

[76]  M. Sheng,et al.  Developmentally Regulated NMDA Receptor-Dependent Dephosphorylation of cAMP Response Element-Binding Protein (CREB) in Hippocampal Neurons , 2000, The Journal of Neuroscience.

[77]  S. Rose,et al.  Effects of early experience on c-fos gene expression in the chick forebrain , 1991, Brain Research.

[78]  Andrew Lemire,et al.  Electroconvulsive Seizures Regulate Gene Expression of Distinct Neurotrophic Signaling Pathways , 2004, The Journal of Neuroscience.

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

[80]  M. Rosenfeld,et al.  REST and Peace for the Neuronal‐Specific Transcriptional Program , 2004, Annals of the New York Academy of Sciences.

[81]  David Baltimore,et al.  NF-κB functions in synaptic signaling and behavior , 2003, Nature Neuroscience.

[82]  Koichi Saito,et al.  Identification of a Novel Basic Helix-Loop-Helix-PAS Factor, NXF, Reveals a Sim2 Competitive, Positive Regulatory Role in Dendritic-Cytoskeleton Modulator Drebrin Gene Expression , 2004, Molecular and Cellular Biology.

[83]  Xiangdong Fang,et al.  Locus control regions. , 2002, Blood.

[84]  W. Catterall,et al.  Calcium Channel Regulation and Presynaptic Plasticity , 2008, Neuron.

[85]  E. Kandel,et al.  cAMP response element-binding protein is activated by Ca2+/calmodulin- as well as cAMP-dependent protein kinase. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[86]  A. Hanauer,et al.  Coffin-Lowry syndrome: clinical and molecular features , 2002, Journal of medical genetics.

[87]  A. Razin,et al.  MeCP2 Deficiency in the Brain Decreases BDNF Levels by REST/CoREST-Mediated Repression and Increases TRKB Production , 2007, Epigenetics.

[88]  M. Sheng,et al.  Targeted Protein Degradation and Synapse Remodeling by an Inducible Protein Kinase , 2003, Science.

[89]  Suzanne Paradis,et al.  The Rac1-GEF Tiam1 Couples the NMDA Receptor to the Activity-Dependent Development of Dendritic Arbors and Spines , 2005, Neuron.

[90]  Eric C. Griffith,et al.  CREB Transcriptional Activity in Neurons Is Regulated by Multiple, Calcium-Specific Phosphorylation Events , 2002, Neuron.

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

[92]  A. Means,et al.  Calmodulin: a prototypical calcium sensor. , 2000, Trends in cell biology.

[93]  W. Zhu,et al.  A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type. , 1998, Genes & development.

[94]  Anirvan Ghosh,et al.  Dendrite Development Regulated by CREST, a Calcium-Regulated Transcriptional Activator , 2004, Science.

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

[96]  S. Grant,et al.  Proteomic analysis of NMDA receptor–adhesion protein signaling complexes , 2000, Nature Neuroscience.

[97]  E. Olson,et al.  CaMKIIδ Isoforms Differentially Affect Calcium Handling but Similarly Regulate HDAC/MEF2 Transcriptional Responses* , 2007, Journal of Biological Chemistry.

[98]  D. Garza,et al.  Activation of cAMP Response Element-Mediated Gene Expression by Regulated Nuclear Transport of TORC Proteins , 2004, Current Biology.

[99]  Anirvan Ghosh,et al.  Regulation of dendritic development by neuronal activity. , 2005, Journal of neurobiology.

[100]  W. Wisden,et al.  Light pulses that shift rhythms induce gene expression in the suprachiasmatic nucleus. , 1990, Science.

[101]  T. Dawson,et al.  Identification of calcium- and nitric oxide-regulated genes by differential analysis of library expression (DAzLE). , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[102]  Alberto Bacci,et al.  A Developmental Switch of AMPA Receptor Subunits in Neocortical Pyramidal Neurons , 2002, The Journal of Neuroscience.

[103]  B. Gaudillière,et al.  Transcription factor Sp4 regulates dendritic patterning during cerebellar maturation , 2007, Proceedings of the National Academy of Sciences.

[104]  Andrew J. Bannister,et al.  The CBP co-activator is a histone acetyltransferase , 1996, Nature.

[105]  E. Nestler,et al.  Histone Modifications at Gene Promoter Regions in Rat Hippocampus after Acute and Chronic Electroconvulsive Seizures , 2004, The Journal of Neuroscience.

[106]  Roberto Malinow,et al.  Increased Expression of the Immediate-Early Gene Arc/Arg3.1 Reduces AMPA Receptor-Mediated Synaptic Transmission , 2006, Neuron.

[107]  W. Regehr,et al.  Developmental Remodeling of the Retinogeniculate Synapse , 2000, Neuron.

[108]  P. Muglia,et al.  The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study. , 2002, American journal of human genetics.

[109]  K. Deisseroth,et al.  Signaling from Synapse to Nucleus: Postsynaptic CREB Phosphorylation during Multiple Forms of Hippocampal Synaptic Plasticity , 1996, Neuron.

[110]  D. Surmeier,et al.  Kalirin-7 Controls Activity-Dependent Structural and Functional Plasticity of Dendritic Spines , 2007, Neuron.

[111]  S. Gabriel,et al.  Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor. , 2002, Molecular psychiatry.

[112]  R. Treisman,et al.  Nuclear Actin Regulates Dynamic Subcellular Localization and Activity of the SRF Cofactor MAL , 2007, Science.

[113]  Michael E Greenberg,et al.  EphB Receptors Interact with NMDA Receptors and Regulate Excitatory Synapse Formation , 2000, Cell.

[114]  M. Greenberg,et al.  Calcium regulation of gene expression in neurons: the mode of entry matters , 1995, Current Opinion in Neurobiology.

[115]  M. Greenberg,et al.  Neurotrophin Regulation of Gene Expression , 1997, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[116]  D. Linden,et al.  Differential Maturation of Climbing Fiber Innervation in Cerebellar Vermis , 2004, The Journal of Neuroscience.

[117]  R. Treisman.  Identification and purification of a polypeptide that binds to the c‐fos serum response element. , 1987, The EMBO journal.

[118]  M. Berridge.  Neuronal Calcium Signaling , 1998, Neuron.

[119]  H. Zoghbi.  Postnatal Neurodevelopmental Disorders: Meeting at the Synapse? , 2003, Science.

[120]  M. Greenberg,et al.  SnapShot: Ca2+-Dependent Transcription in Neurons , 2008, Cell.

[121]  L. Feig,et al.  Age-dependent Participation of Ras-GRF Proteins in Coupling Calcium-permeable AMPA Glutamate Receptors to Ras/Erk Signaling in Cortical Neurons* , 2006, Journal of Biological Chemistry.

[122]  H. Jang,et al.  Cabin1 Represses MEF2 Transcriptional Activity by Association with a Methyltransferase, SUV39H1* , 2007, Journal of Biological Chemistry.

[123]  R. Dolmetsch,et al.  Signaling to the Nucleus by an L-type Calcium Channel-Calmodulin Complex Through the MAP Kinase Pathway , 2001, Science.

[124]  Mark Mayford,et al.  Nuclear Calcium/Calmodulin Regulates Memory Consolidation , 2004, The Journal of Neuroscience.

[125]  Laurent Groc,et al.  In vivo blockade of neural activity alters dendritic development of neonatal CA1 pyramidal cells , 2002, The European journal of neuroscience.

[126]  M. Dalva,et al.  Modulation of NMDA Receptor- Dependent Calcium Influx and Gene Expression Through EphB Receptors , 2001, Science.

[127]  Brian J. Wiltgen,et al.  NF-kappa B functions in synaptic signaling and behavior. , 2003, Nature neuroscience.

[128]  Anirvan Ghosh,et al.  Calcium Regulation of Dendritic Growth via CaM Kinase IV and CREB-Mediated Transcription , 2002, Neuron.

[129]  Elly Nedivi,et al.  Numerous candidate plasticity-related genes revealed by differential cDNA cloning , 1993, Nature.

[130]  Dan Kerley,et al.  A Golgi-Cox morphological analysis of neuronal changes induced by environmental enrichment. , 2003, Brain research. Developmental brain research.

[131]  H. Youn,et al.  Apoptosis of T cells mediated by Ca2+-induced release of the transcription factor MEF2. , 1999, Science.

[132]  J. Yates,et al.  Primary Structure and Function of an A Kinase Anchoring Protein Associated with Calcium Channels , 1998, Neuron.

[133]  T. Soderling,et al.  Phosphorylation of CBP Mediates Transcriptional Activation by Neural Activity and CaM Kinase IV , 2002, Neuron.

[134]  A. Riesen,et al.  Evironmental effects on cortical dendritic fields. I. Rearing in the dark. , 1968, Journal of anatomy.

[135]  D. Collier,et al.  Association of BDNF with anorexia, bulimia and age of onset of weight loss in six European populations. , 2004, Human molecular genetics.

[136]  Alcino J. Silva,et al.  Calmodulin-Kinases: Modulators of Neuronal Development and Plasticity , 2008, Neuron.

[137]  Thomas Lemberger,et al.  SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viability , 2005, Nature Neuroscience.

[138]  K. Deisseroth,et al.  L-type calcium channels and GSK-3 regulate the activity of NF-ATc4 in hippocampal neurons , 1999, Nature.

[139]  Steven Finkbeiner,et al.  Ca2+ Influx Regulates BDNF Transcription by a CREB Family Transcription Factor-Dependent Mechanism , 1998, Neuron.

[140]  Michael E. Greenberg,et al.  A Calcium-Responsive Transcription Factor, CaRF, that Regulates Neuronal Activity-Dependent Expression of BDNF , 2002, Neuron.

[141]  S. Gabriel,et al.  Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus , 2002, Molecular Psychiatry.

[142]  E. Kandel,et al.  A Role in Learning for SRF: Deletion in the Adult Forebrain Disrupts LTD and the Formation of an Immediate Memory of a Novel Context , 2006, Neuron.

[143]  T. Curran,et al.  Mapping patterns of c-fos expression in the central nervous system after seizure. , 1987, Science.

[144]  B. Sabatini,et al.  Calcium Signaling in Dendrites and Spines: Practical and Functional Considerations , 2008, Neuron.

[145]  R. Kraft,et al.  MAPKAP Kinase 2 Phosphorylates Serum Response Factor in Vitro and in Vivo* , 1999, The Journal of Biological Chemistry.

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

[147]  H. Bading,et al.  CBP: a signal-regulated transcriptional coactivator controlled by nuclear calcium and CaM kinase IV. , 1998, Science.

[148]  Gail Mandel,et al.  Defining the CREB Regulon A Genome-Wide Analysis of Transcription Factor Regulatory Regions , 2004, Cell.

[149]  M. Greenberg,et al.  CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases. , 1991, Science.

[150]  W. Catterall.  Structure and regulation of voltage-gated Ca2+ channels. , 2000, Annual review of cell and developmental biology.

[151]  Margit Burmeister,et al.  A BDNF Coding Variant is Associated with the NEO Personality Inventory Domain Neuroticism, a Risk Factor for Depression , 2003, Neuropsychopharmacology.

[152]  Kevin G Becker,et al.  Identification and analysis of plasticity-induced late-response genes , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[153]  H. Scharfman,et al.  Brain-derived neurotrophic factor. , 2004, Growth factors.

[154]  M. Saarma,et al.  Multiple promoters direct tissue-specific expression of the rat BDNF gene , 1993, Neuron.

[155]  A. West,et al.  Calcium regulation of neuronal gene expression , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[156]  Olga Varlamova,et al.  A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[157]  H. Cline,et al.  Dendritic arbor development and synaptogenesis , 2001, Current Opinion in Neurobiology.

[158]  H. Cline,et al.  Promotion of dendritic growth by CPG15, an activity-induced signaling molecule. , 1998, Science.

[159]  Masatoshi Hagiwara,et al.  Phosphorylated CREB binds specifically to the nuclear protein CBP , 1993, Nature.

[160]  G. Carmignoto,et al.  Activity-dependent decrease in NMDA receptor responses during development of the visual cortex. , 1992, Science.

[161]  Hideaki Ando,et al.  An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP , 2008, Proceedings of the National Academy of Sciences.

[162]  N. Hardingham,et al.  Nuclear Ca2+ and the cAMP Response Element-Binding Protein Family Mediate a Late Phase of Activity-Dependent Neuroprotection , 2005, The Journal of Neuroscience.

[163]  J. Sanes,et al.  Development of the vertebrate neuromuscular junction. , 1999, Annual review of neuroscience.

[164]  Colin A. Johnson,et al.  Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex , 1998, Nature.