Heterosynaptic Molecular Dynamics: Locally Induced Propagating Synaptic Accumulation of CaM Kinase II

Calcium-calmodulin-dependent protein kinase II (CaMKII) is a key mediator of synaptic plasticity and learning. Global pyramidal cell glutamate stimulation induces translocation of CaMKII from dendritic shafts to spines. Here we show that local dendritic stimulation by puffing glutamate onto a region containing 7-32 synapses induces translocation of CaMKII to synapses initially at the puff site but that translocation subsequently spreads within dendrites to the distal dendrite arbor, resulting in a persistent, widespread synaptic accumulation. This locally induced propagating synaptic (L-IPS) accumulation of CaMKII requires activation of NMDA receptors and L-type Ca(2+) channels and is preceded by a Ca(2+) spike. L-IPS translocation of CaMKII alters biochemical signaling and is associated with an increase in AMPA receptor GluR1 at both stimulated and nonstimulated synapses and thus provides a molecular mechanism for heterosynaptic plasticity.

[1]  R. Nicoll,et al.  Postsynaptically Silent Synapses in Single Neuron Cultures , 1998, Neuron.

[2]  Andy Hudmon,et al.  Neuronal CA2+/calmodulin-dependent protein kinase II: the role of structure and autoregulation in cellular function. , 2002, Annual review of biochemistry.

[3]  P. Schwindt,et al.  Local and propagated dendritic action potentials evoked by glutamate iontophoresis on rat neocortical pyramidal neurons. , 1997, Journal of neurophysiology.

[4]  J. Lisman,et al.  The molecular basis of CaMKII function in synaptic and behavioural memory , 2002, Nature Reviews Neuroscience.

[5]  D. Monaghan,et al.  Extrasynaptic NR2B and NR2D subunits of NMDA receptors shape ‘superslow’ afterburst EPSC in rat hippocampus , 2004, The Journal of physiology.

[6]  J. H. Connor,et al.  Molecular memory by reversible translocation of calcium/calmodulin-dependent protein kinase II , 2000, Nature Neuroscience.

[7]  Scott M Thompson,et al.  Unique roles of SK and Kv4.2 potassium channels in dendritic integration. , 2004, Neuron.

[8]  Karel Svoboda,et al.  Locally dynamic synaptic learning rules in pyramidal neuron dendrites , 2007, Nature.

[9]  D. Kullmann,et al.  NMDA receptor‐dependent long‐term potentiation in mouse hippocampal interneurons shows a unique dependence on Ca2+/calmodulin‐dependent kinases , 2007, The Journal of physiology.

[10]  Joseph E LeDoux,et al.  Heterosynaptic Long-Term Potentiation of Inhibitory Interneurons in the Lateral Amygdala , 2004, The Journal of Neuroscience.

[11]  H. Okado,et al.  Continual remodeling of postsynaptic density and its regulation by synaptic activity , 1999, Nature Neuroscience.

[12]  R. Colbran,et al.  Targeting of calcium/calmodulin-dependent protein kinase II. , 2004, The Biochemical journal.

[13]  Paul De Koninck,et al.  Transition from Reversible to Persistent Binding of CaMKII to Postsynaptic Sites and NR2B , 2006, The Journal of Neuroscience.

[14]  Ann Marie Craig,et al.  Postsynaptic protein mobility in dendritic spines: Long-term regulation by synaptic NMDA receptor activation , 2006, Molecular and Cellular Neuroscience.

[15]  Mark E. Anderson,et al.  L-type Ca2+ channel facilitation mediated by phosphorylation of the beta subunit by CaMKII. , 2006, Molecular cell.

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

[17]  Mark E. Anderson,et al.  RETRACTED: L-Type Ca2+ Channel Facilitation Mediated by Phosphorylation of the β Subunit by CaMKII , 2006 .

[18]  D. Rusakov,et al.  CaMKII translocation requires local NMDA receptor‐mediated Ca2+ signaling , 2006, The EMBO journal.

[19]  Balazs Rozsa,et al.  Distance-Dependent Scaling of Calcium Transients Evoked by Backpropagating Spikes and Synaptic Activity in Dendrites of Hippocampal Interneurons , 2004, The Journal of Neuroscience.

[20]  D. Muller,et al.  Heterosynaptic interactions between UP and LTD in CA1 hippocampal slices , 1995, Neuron.

[21]  K. Shen,et al.  Dynamic control of CaMKII translocation and localization in hippocampal neurons by NMDA receptor stimulation. , 1999, Science.

[22]  Wei-Yang Lu,et al.  Activation of Synaptic NMDA Receptors Induces Membrane Insertion of New AMPA Receptors and LTP in Cultured Hippocampal Neurons , 2001, Neuron.

[23]  D. Tank,et al.  In vivo dendritic calcium dynamics in deep-layer cortical pyramidal neurons , 1999, Nature Neuroscience.

[24]  M Neal Waxham,et al.  A Mechanism for Ca2+/Calmodulin-Dependent Protein Kinase II Clustering at Synaptic and Nonsynaptic Sites Based on Self-Association , 2005, The Journal of Neuroscience.

[25]  Ann Marie Craig,et al.  Synapse composition and organization following chronic activity blockade in cultured hippocampal neurons , 2005, The Journal of comparative neurology.

[26]  F. Engert,et al.  Synapse specificity of long-term potentiation breaks down at short distances , 1997, Nature.

[27]  N. Spruston.  Pyramidal neurons: dendritic structure and synaptic integration , 2008, Nature Reviews Neuroscience.

[28]  J. Rostas,et al.  Phosphorylation of CaMKII at Thr253 occurs in vivo and enhances binding to isolated postsynaptic densities , 2006, Journal of neurochemistry.

[29]  A. Nairn,et al.  Oligomerization states of the association domain and the holoenyzme of Ca2+/CaM kinase II , 2006, The FEBS journal.

[30]  James Kim,et al.  CaMKII tethers to L-type Ca2+ channels, establishing a local and dedicated integrator of Ca2+ signals for facilitation , 2005, The Journal of cell biology.

[31]  S. H. Lee,et al.  Differences in Ca2+ buffering properties between excitatory and inhibitory hippocampal neurons from the rat , 2000, The Journal of physiology.

[32]  I. Módy,et al.  The absence of a major Ca2+ signaling pathway in GABAergic neurons of the hippocampus. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[33]  T. Soderling,et al.  Cellular Signaling through Multifunctional Ca2+/Calmodulin-dependent Protein Kinase II* , 2001, The Journal of Biological Chemistry.

[34]  R. Malenka,et al.  Substrate Localization Creates Specificity in Calcium/Calmodulin-dependent Protein Kinase II Signaling at Synapses* , 2006, Journal of Biological Chemistry.

[35]  Yitzhak Schiller,et al.  NMDA receptor-mediated dendritic spikes and coincident signal amplification , 2001, Current Opinion in Neurobiology.

[36]  J. Swann,et al.  Distally Directed Dendrotoxicity Induced by Kainic Acid in Hippocampal Interneurons of Green Fluorescent Protein-Expressing Transgenic Mice , 2002, The Journal of Neuroscience.

[37]  G. Buzsáki,et al.  Dendritic Spikes Are Enhanced by Cooperative Network Activity in the Intact Hippocampus , 1998, The Journal of Neuroscience.

[38]  M. Inagaki,et al.  Activation of Ca2+/calmodulin-dependent protein kinase II within post-synaptic dendritic spines of cultured hippocampal neurons. , 2000, The Journal of biological chemistry.