Hippocampal LTP Is Accompanied by Enhanced F-Actin Content within the Dendritic Spine that Is Essential for Late LTP Maintenance In Vivo

The dendritic spine is an important site of neuronal plasticity and contains extremely high levels of cytoskeletal actin. However, the dynamics of the actin cytoskeleton during synaptic plasticity and its in vivo function remain unclear. Here we used an in vivo dentate gyrus LTP model to show that LTP induction is associated with actin cytoskeletal reorganization characterized by a long-lasting increase in F-actin content within dendritic spines. This increase in F-actin content is dependent on NMDA receptor activation and involves the inactivation of actin depolymerizing factor/cofilin. Inhibition of actin polymerization with latrunculin A impaired late phase of LTP without affecting the initial amplitude and early maintenance of LTP. These observations suggest that mechanisms regulating the spine actin cytoskeleton contribute to the persistence of LTP.

[1]  A. Hjorth-Simonsen,et al.  Origin and termination of the hippocampal perforant path in the rat studied by silver impregnation , 1972, The Journal of comparative neurology.

[2]  I. Yahara,et al.  Phosphorylation of Ser‐3 of cofilin regulates its essential function on actin , 1996, Genes to cells : devoted to molecular & cellular mechanisms.

[3]  R. Patterson,et al.  Store-Operated Ca2+ Entry Evidence for a Secretion-like Coupling Model , 1999, Cell.

[4]  M. Carlier,et al.  Control of Actin Dynamics in Cell Motility , 2022 .

[5]  U. Hanisch,et al.  Cytoskeletal dynamics in dendritic spines: direct modulation by glutamate receptors? , 1999, Trends in Neurosciences.

[6]  Oswald Steward,et al.  Synaptic Activation Causes the mRNA for the IEG Arc to Localize Selectively near Activated Postsynaptic Sites on Dendrites , 1998, Neuron.

[7]  K. Inokuchi,et al.  vesl, a gene encoding VASP/Ena family related protein, is upregulated during seizure, long‐term potentiation and synaptogenesis 1 , 1997, FEBS letters.

[8]  M E Martone,et al.  Selective localization of high concentrations of F‐actin in subpopulations of dendritic spines in rat central nervous system: A three‐dimensional electron microscopic study , 2001, The Journal of comparative neurology.

[9]  M. Sheng,et al.  Regulation of Dendritic Spine Morphology by SPAR, a PSD-95-Associated RapGAP , 2001, Neuron.

[10]  R. Kelly,et al.  Molecular Links between Endocytosis and the Actin Cytoskeleton , 2000, The Journal of cell biology.

[11]  E. Kandel,et al.  A Macromolecular Synthesis-Dependent Late Phase of Long-Term Potentiation Requiring cAMP in the Medial Perforant Pathway of Rat Hippocampal Slices , 1996, The Journal of Neuroscience.

[12]  Yasushi Miyashita,et al.  Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons , 2001, Nature Neuroscience.

[13]  R. Racine,et al.  The degree of potentiation is associated with synaptic number during the maintenance of long-term potentiation in the rat dentate gyrus , 1998, Brain Research.

[14]  U. Frey,et al.  Somatodendritic expression of an immediate early gene is regulated by synaptic activity. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Y. Sakaki,et al.  Cataloging altered gene expression during rat hippocampal long-term potentiation by means of differential display , 1998, Neuroscience Letters.

[16]  T. Uemura,et al.  Control of Actin Reorganization by Slingshot, a Family of Phosphatases that Dephosphorylate ADF/Cofilin , 2002, Cell.

[17]  A. Matus,et al.  Actin-based plasticity in dendritic spines. , 2000, Science.

[18]  E. Fifková,et al.  Actin matrix of dendritic spines, synaptic plasticity, and long-term potentiation. , 1992, International review of cytology.

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

[20]  K. Inokuchi,et al.  Regulated expression of an actin‐associated protein, synaptopodin, during long‐term potentiation , 2001, Journal of neurochemistry.

[21]  R. Yuste,et al.  Regulation of dendritic spine morphology by the rho family of small GTPases: antagonistic roles of Rac and Rho. , 2000, Cerebral cortex.

[22]  T. Bliss,et al.  Long-term potentiation in the dentate gyrus: induction and increased glutamate release are blocked by d(−)aminophosphonovalerate , 1987, Neuroscience.

[23]  K. E. Smith,et al.  Regulation of A-Kinase Anchoring Protein 79/150–cAMP-Dependent Protein Kinase Postsynaptic Targeting by NMDA Receptor Activation of Calcineurin and Remodeling of Dendritic Actin , 2002, The Journal of Neuroscience.

[24]  W. Abraham,et al.  Correlation between the induction of an immediate early gene,zif/268, and long-term potentiation in the dentate gyrus , 1992, Brain Research.

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

[26]  S. Narumiya,et al.  Cofilin phosphorylation by protein kinase testicular protein kinase 1 and its role in integrin-mediated actin reorganization and focal adhesion formation. , 2001, Molecular biology of the cell.

[27]  M. Carlier.  Dynamic actin , 1993, Current Biology.

[28]  Roberto Malinow,et al.  Subunit-Specific Rules Governing AMPA Receptor Trafficking to Synapses in Hippocampal Pyramidal Neurons , 2001, Cell.

[29]  A. Hall,et al.  Rho GTPases and their effector proteins. , 2000, The Biochemical journal.

[30]  B. Molyneaux,et al.  Myosin V in the brain: mutations lead to neurological defects , 1998, Brain Research Reviews.

[31]  Ann Y. Nakayama,et al.  Small GTPases Rac and Rho in the Maintenance of Dendritic Spines and Branches in Hippocampal Pyramidal Neurons , 2000, The Journal of Neuroscience.

[32]  J. Fiala,et al.  Polyribosomes Redistribute from Dendritic Shafts into Spines with Enlarged Synapses during LTP in Developing Rat Hippocampal Slices , 2002, Neuron.

[33]  A. Craig,et al.  Role of Actin in Anchoring Postsynaptic Receptors in Cultured Hippocampal Neurons: Differential Attachment of NMDA versus AMPA Receptors , 1998, The Journal of Neuroscience.

[34]  P. Worley,et al.  Arcadlin Is a Neural Activity-regulated Cadherin Involved in Long Term Potentiation* , 1999, The Journal of Biological Chemistry.

[35]  M. Fischer,et al.  Rapid Actin-Based Plasticity in Dendritic Spines , 1998, Neuron.

[36]  E. Nishida,et al.  Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization , 1998, Nature.

[37]  E. A.,et al.  Actin in the nervous system , 1985 .

[38]  B. L. McNaughton,et al.  Evidence for two physiologically distinct perforant pathways to the fascia dentata , 1980, Brain Research.

[39]  D. Bray,et al.  Distribution and cellular localization of actin depolymerizing factor , 1987, The Journal of cell biology.

[40]  John E. Lisman,et al.  A Role of Actin Filament in Synaptic Transmission and Long-Term Potentiation , 1999, The Journal of Neuroscience.

[41]  Venkatesh N. Murthy,et al.  Rapid turnover of actin in dendritic spines and its regulation by activity , 2002, Nature Neuroscience.

[42]  Karl Deisseroth,et al.  Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology , 2001, Nature Neuroscience.

[43]  J. Bamburg,et al.  Reactivation of Phosphorylated Actin Depolymerizing Factor and Identification of the Regulatory Site (*) , 1995, The Journal of Biological Chemistry.

[44]  Mark von Zastrow,et al.  Role of ampa receptor endocytosis in synaptic plasticity , 2001, Nature Reviews Neuroscience.

[45]  Carol A. Barnes,et al.  Expression of a mitogen-inducible cyclooxygenase in brain neurons: Regulation by synaptic activity and glucocorticoids , 1993, Neuron.

[46]  S. Narumiya,et al.  Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. , 1999, Science.

[47]  D. C. Edwards,et al.  Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics , 1999, Nature Cell Biology.

[48]  R. Nicoll,et al.  Contribution of cytoskeleton to the internalization of AMPA receptors. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[49]  Eric R. Kandel,et al.  Tissue-plasminogen activator is induced as an immediate–early gene during seizure, kindling and long-term potentiation , 1993, Nature.

[50]  E. Fifková.  Actin in the nervous system , 1985, Brain Research Reviews.

[51]  E. Kandel,et al.  Requirement of a critical period of transcription for induction of a late phase of LTP. , 1994, Science.

[52]  F. Morrell,et al.  Synapse restructuring associated with the maintenance phase of hippocampal long‐term potentiation , 1996, The Journal of comparative neurology.

[53]  H Terada,et al.  A High-Efficiency Protein Transduction System Demonstrating the Role of PKA in Long-Lasting Long-Term Potentiation , 2001, The Journal of Neuroscience.

[54]  E. Kandel,et al.  Toward a molecular definition of long-term memory storage. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[55]  M. Fischer,et al.  Glutamate receptors regulate actin-based plasticity in dendritic spines , 2000, Nature Neuroscience.

[56]  S. Kaech,et al.  Cytoskeletal microdifferentiation: A mechanism for organizing morphological plasticity in dendrites , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[57]  P. De Camilli,et al.  Phosphoinositides in membrane traffic at the synapse. , 2001, Journal of cell science.

[58]  U. Frey,et al.  Influence of actinomycin D, a RNA synthesis inhibitor, on long‐term potentiation in rat hippocampal neurons in vivo and in vitro. , 1996, The Journal of physiology.

[59]  K. Inokuchi,et al.  Identification and Cataloging of Genes Induced by Long‐Lasting Long‐Term Potentiation in Awake Rats , 2000, Journal of neurochemistry.

[60]  B. McNaughton,et al.  Physiological identification and analysis of dentate granule cell responses to stimulation of the medial and lateral perforant pathways in the rat , 1977, The Journal of comparative neurology.

[61]  Roberto Malinow,et al.  LTP mechanisms: from silence to four-lane traffic , 2000, Current Opinion in Neurobiology.

[62]  Y. Goshima,et al.  Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse , 2001, Nature Neuroscience.

[63]  S. Halpain,et al.  Actin and the agile spine: how and why do dendritic spines dance? , 2000, Trends in Neurosciences.

[64]  Marie-France Carlier,et al.  Mechanism of Actin-Based Motility , 2001, Science.

[65]  K. Inokuchi,et al.  Novel Members of the Vesl/Homer Family of PDZ Proteins That Bind Metabotropic Glutamate Receptors* , 1998, The Journal of Biological Chemistry.

[66]  M. Sheng,et al.  AMPA Receptor Trafficking and the Control of Synaptic Transmission , 2001, Cell.

[67]  J. Lisman,et al.  A Model of Synaptic Memory A CaMKII/PP1 Switch that Potentiates Transmission by Organizing an AMPA Receptor Anchoring Assembly , 2001, Neuron.

[68]  R. Huganir,et al.  The Neuronal Rho-GEF Kalirin-7 Interacts with PDZ Domain–Containing Proteins and Regulates Dendritic Morphogenesis , 2001, Neuron.

[69]  L. Liotta,et al.  Sensitive immunoassay of tissue cell proteins procured by laser capture microdissection. , 2000, The American journal of pathology.

[70]  J. Bamburg,et al.  Increase in Neurite Outgrowth Mediated by Overexpression of Actin Depolymerizing Factor , 2000, The Journal of Neuroscience.

[71]  Carol A Barnes,et al.  Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites , 1995, Neuron.

[72]  I. Spector,et al.  Latrunculins--novel marine macrolides that disrupt microfilament organization and affect cell growth: I. Comparison with cytochalasin D. , 1989, Cell motility and the cytoskeleton.

[73]  J. Cooper,et al.  Effects of cytochalasin and phalloidin on actin , 1987, The Journal of cell biology.

[74]  S. Halpain,et al.  Dynamic actin filaments are required for stable long-term potentiation (LTP) in area CA1 of the hippocampus. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

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

[76]  R. Nicoll,et al.  Postsynaptic membrane fusion and long-term potentiation. , 1998, Science.

[77]  Michael J. Sailor,et al.  Remodeling of Synaptic Actin Induced by Photoconductive Stimulation , 2001, Cell.

[78]  D. Muller,et al.  Induction of long-term potentiation is associated with major ultrastructural changes of activated synapses. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[79]  K. Inokuchi,et al.  Increase in activin βA mRNA in rat hippocampus during long‐term potentiation , 1996 .

[80]  O. Steward,et al.  Topographic organization of the projections from the entorhinal area to the hippocampal formation of the rat , 1976, The Journal of comparative neurology.

[81]  E. Ziff.  Enlightening the Postsynaptic Density , 1997, Neuron.

[82]  J. Bamburg,et al.  Regulating actin-filament dynamics in vivo. , 2000, Trends in biochemical sciences.

[83]  D. Schafer,et al.  Coupling actin dynamics and membrane dynamics during endocytosis. , 2002, Current opinion in cell biology.

[84]  E. Kandel,et al.  Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. , 1993, Science.

[85]  K. Svoboda,et al.  Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex , 2002, Nature.

[86]  J. Macdonald,et al.  Abnormal Spine Morphology and Enhanced LTP in LIMK-1 Knockout Mice , 2002, Neuron.

[87]  A. Matus,et al.  High actin concentrations in brain dendritic spines and postsynaptic densities. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[88]  K. Svoboda,et al.  Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. , 1999, Science.

[89]  T. Obinata,et al.  A cofilin-like protein is involved in the regulation of actin assembly in developing skeletal muscle. , 1989, Journal of biochemistry.

[90]  J. M. Williams,et al.  Correlations between immediate early gene induction and the persistence of long-term potentiation , 1993, Neuroscience.

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

[92]  P. Andersen,et al.  Long-term potentiation is associated with new excitatory spine synapses on rat dentate granule cells. , 1996, Learning & memory.

[93]  P. Caroni,et al.  Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase , 1998, Nature.

[94]  R. Malinow,et al.  Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction. , 2000, Science.

[95]  M. Krug,et al.  Anisomycin blocks the late phase of long-term potentiation in the dentate gyrus of freely moving rats , 1984, Brain Research Bulletin.

[96]  M. Ishida,et al.  Latexin expression in smaller diameter primary sensory neurons in the rat , 1998, Brain Research.

[97]  C. Barnes,et al.  Homer: a protein that selectively binds metabotropic glutamate receptors , 1997, Nature.

[98]  A. Hjorth-Simonsen,et al.  Projection of the lateral part of the entorhinal area to the hippocampus and fascia dentata , 1972, The Journal of comparative neurology.