Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology

Memory storage in mammalian neurons probably depends on both biochemical events and morphological alterations in dendrites. Here we report an activity-dependent stabilization of the MAP kinase (MAPK) pathway, prominent in hippocampal dendrites. The longevity of the signal in these dendrites was increased to hours when multiple spaced stimuli were used. Likewise, spaced stimuli and MAPK activation were critical for protrusion of new dendritic filopodia that also remained stable for hours. Our experiments define a new role for stimulus-specific responses of MAPK signaling in activity-dependent neuronal plasticity. The local biochemical signaling in dendrites complements MAPK signaling in gene expression. Together, these processes may support long-lasting behavioral changes.

[1]  F. Edwards,et al.  Anatomy and electrophysiology of fast central synapses lead to a structural model for long-term potentiation. , 1995, Physiological reviews.

[2]  H. Yao,et al.  cAMP Activates MAP Kinase and Elk-1 through a B-Raf- and Rap1-Dependent Pathway , 1997, Cell.

[3]  E. Schuman,et al.  mRNA Trafficking and Local Protein Synthesis at the Synapse , 1999, Neuron.

[4]  U. Frey,et al.  Synaptic tagging and long-term potentiation , 1997, Nature.

[5]  R. Tsien,et al.  Activity-dependent regulation of synaptic clustering in a hippocampal culture system. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[6]  J. David Sweatt,et al.  The MAPK cascade is required for mammalian associative learning , 1998, Nature Neuroscience.

[7]  T. Murphy,et al.  Differential regulation of calcium/calmodulin-dependent protein kinase II and p42 MAP kinase activity by synaptic transmission , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  Eric R Kandel,et al.  MAP Kinase Translocates into the Nucleus of the Presynaptic Cell and Is Required for Long-Term Facilitation in Aplysia , 1997, Neuron.

[9]  E. Kandel,et al.  Mutation in the Phosphorylation Sites of MAP Kinase Blocks Learning-Related Internalization of apCAM in Aplysia Sensory Neurons , 1997, Neuron.

[10]  M E Greenberg,et al.  Stimulation of protein tyrosine phosphorylation by NMDA receptor activation , 1991, Science.

[11]  Ravi Iyengar Gating by Cyclic AMP: Expanded Role for an Old Signaling Pathway , 1996, Science.

[12]  Eric R Kandel,et al.  ERK Plays a Regulatory Role in Induction of LTP by Theta Frequency Stimulation and Its Modulation by β-Adrenergic Receptors , 1999, Neuron.

[13]  J. Pouysségur,et al.  Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation. , 1999, Science.

[14]  K. Deisseroth,et al.  CREB Phosphorylation and Dephosphorylation: A Ca2+- and Stimulus Duration–Dependent Switch for Hippocampal Gene Expression , 1996, Cell.

[15]  H. Cline,et al.  Stabilization of dendritic arbor structure in vivo by CaMKII. , 1998, Science.

[16]  Alcino J. Silva,et al.  Spaced training induces normal long-term memory in CREB mutant mice , 1997, Current Biology.

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

[18]  T. Carew,et al.  Differential induction of long-term synaptic facilitation by spaced and massed applications of serotonin at sensory neuron synapses of Aplysia californica. , 1998, Learning & memory.

[19]  P. Dash,et al.  A Mitogen-Activated Protein Kinase Cascade in the CA1/CA2 Subfield of the Dorsal Hippocampus Is Essential for Long-Term Spatial Memory , 1999, The Journal of Neuroscience.

[20]  R. Yuste,et al.  Developmental regulation of spine motility in the mammalian central nervous system. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

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

[22]  Scott T. Wong,et al.  Cross Talk between ERK and PKA Is Required for Ca2+ Stimulation of CREB-Dependent Transcription and ERK Nuclear Translocation , 1998, Neuron.

[23]  W. Quinn,et al.  Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila , 1994, Cell.

[24]  D. Rusakov,et al.  Repeated confocal imaging of individual dendritic spines in the living hippocampal slice: evidence for changes in length and orientation associated with chemically induced LTP , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[25]  Marco Capogna,et al.  Miniature synaptic events maintain dendritic spines via AMPA receptor activation , 1999, Nature Neuroscience.

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

[27]  M. Segal,et al.  Morphological plasticity of dendritic spines in central neurons is mediated by activation of cAMP response element binding protein. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[28]  A. Bridges,et al.  A synthetic inhibitor of the mitogen-activated protein kinase cascade. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[29]  M. Greenberg,et al.  Membrane depolarization and calcium influx stimulate MEK and MAP kinase via activation of Ras , 1994, Neuron.

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

[31]  S. Grant,et al.  A role for the Ras signalling pathway in synaptic transmission and long-term memory , 1997, Nature.

[32]  Joseph E LeDoux,et al.  Memory consolidation for contextual and auditory fear conditioning is dependent on protein synthesis, PKA, and MAP kinase. , 1999, Learning & memory.

[33]  M. Kennedy,et al.  A Synaptic Ras-GTPase Activating Protein (p135 SynGAP) Inhibited by CaM Kinase II , 1998, Neuron.

[34]  K. Deisseroth,et al.  Translocation of calmodulin to the nucleus supports CREB phosphorylation in hippocampal neurons , 1998, Nature.

[35]  E. Kandel,et al.  cAMP contributes to mossy fiber LTP by initiating both a covalently mediated early phase and macromolecular synthesis-dependent late phase , 1994, Cell.

[36]  J. David Sweatt,et al.  A Requirement for the Mitogen-activated Protein Kinase Cascade in Hippocampal Long Term Potentiation* , 1997, The Journal of Biological Chemistry.

[37]  A. Gingras,et al.  eIF4E activity is regulated at multiple levels. , 1999, The international journal of biochemistry & cell biology.

[38]  F. Hobbs,et al.  Identification of a Novel Inhibitor of Mitogen-activated Protein Kinase Kinase* , 1998, The Journal of Biological Chemistry.

[39]  M. Freissmuth,et al.  Activation of Mitogen-activated Protein Kinase by the A2A-adenosine Receptor via a rap1-dependent and via a p21 ras -dependent Pathway* , 1999, The Journal of Biological Chemistry.

[40]  R. Douglas Fields,et al.  Action Potential-Dependent Regulation of Gene Expression: Temporal Specificity in Ca2+, cAMP-Responsive Element Binding Proteins, and Mitogen-Activated Protein Kinase Signaling , 1997, The Journal of Neuroscience.

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

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

[43]  T. Soderling,et al.  Regulation of mitogen-activated protein kinases by a calcium/calmodulin-dependent protein kinase cascade. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[44]  J. Fiala,et al.  Critical assessment of the involvement of perforations, spinules, and spine branching in hippocampal synapse formation , 1998, The Journal of comparative neurology.

[45]  Stephen J. Smith,et al.  Evidence for a Role of Dendritic Filopodia in Synaptogenesis and Spine Formation , 1996, Neuron.

[46]  E. Kandel,et al.  A Transient, Neuron-Wide Form of CREB-Mediated Long-Term Facilitation Can Be Stabilized at Specific Synapses by Local Protein Synthesis , 1999, Cell.

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

[48]  J. Sweatt,et al.  The Mitogen-Activated Protein Kinase Cascade Couples PKA and PKC to cAMP Response Element Binding Protein Phosphorylation in Area CA1 of Hippocampus , 1999, The Journal of Neuroscience.

[49]  E R Kandel,et al.  Repeated pulses of serotonin required for long-term facilitation activate mitogen-activated protein kinase in sensory neurons of Aplysia. , 1998, Proceedings of the National Academy of Sciences of the United States of America.