Regulation of AMPA receptor lateral movements

An essential feature in the modulation of the efficacy of synaptic transmission is rapid changes in the number of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors at post-synaptic sites on neurons. Regulation of receptor endo- and exocytosis has been shown to be involved in this process. Whether regulated lateral diffusion of receptors in the plasma membrane also participates in receptor exchange to and from post-synaptic sites remains unknown. We analysed the lateral mobility of native AMPA receptors containing the glutamate receptor subunit GluR2 in rat cultured hippocampal neurons, using single-particle tracking and video microscopy. Here we show that AMPA receptors alternate within seconds between rapid diffusive and stationary behaviour. During maturation of neurons, stationary periods increase in frequency and length, often in spatial correlation with synaptic sites. Raising intracellular calcium, a central element in synaptic plasticity, triggers rapid receptor immobilization and local accumulation on the neuronal surface. We suggest that calcium influx prevents AMPA receptors from diffusing, and that lateral receptor diffusion to and from synaptic sites acts in the rapid and controlled regulation of receptor numbers at synapses.

[1]  P. Rakic.  Specification of cerebral cortical areas. , 1988, Science.

[2]  E. G. Jones,et al.  GABAergic neurons and their role in cortical plasticity in primates. , 1993, Cerebral cortex.

[3]  P. De Camilli,et al.  Synaptogenesis in hippocampal cultures: evidence indicating that axons and dendrites become competent to form synapses at different stages of neuronal development , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[4]  K. Jacobson,et al.  Detection of temporary lateral confinement of membrane proteins using single-particle tracking analysis. , 1995, Biophysical journal.

[5]  M E Greenberg,et al.  Calcium signaling in neurons: molecular mechanisms and cellular consequences. , 1995, Science.

[6]  J. Olivo,et al.  Dendroaxonal Transcytosis of Transferrin in Cultured Hippocampal and Sympathetic Neurons , 1997, The Journal of Neuroscience.

[7]  K. Jacobson,et al.  Structural mosaicism on the submicron scale in the plasma membrane. , 1998, Biophysical journal.

[8]  Mark von Zastrow,et al.  Rapid redistribution of glutamate receptors contributes to long-term depression in hippocampal cultures , 1999, Nature Neuroscience.

[9]  R. Zucker,et al.  Selective induction of LTP and LTD by postsynaptic [Ca2+]i elevation. , 1999, Journal of neurophysiology.

[10]  Andreas Lüthi,et al.  Hippocampal LTD Expression Involves a Pool of AMPARs Regulated by the NSF–GluR2 Interaction , 1999, Neuron.

[11]  G. Collingridge,et al.  Surface Expression of AMPA Receptors in Hippocampal Neurons Is Regulated by an NSF-Dependent Mechanism , 1999, Neuron.

[12]  Mark von Zastrow,et al.  Role of AMPA Receptor Cycling in Synaptic Transmission and Plasticity , 1999, Neuron.

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

[14]  A. Kakita,et al.  Patterns and Dynamics of SVZ Cell Migration in the Postnatal Forebrain Monitoring Living Progenitors in Slice Preparations , 1999, Neuron.

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

[16]  C. Walsh,et al.  Neuronal migration disorders: from genetic diseases to developmental mechanisms , 2000, Trends in Neurosciences.

[17]  T. Preuss.  Taking the Measure of Diversity: Comparative Alternatives to the Model-Animal Paradigm in Cortical Neuroscience , 2000, Brain, Behavior and Evolution.

[18]  A. Dautry‐Varsat,et al.  Mapping of Eps15 Domains Involved in Its Targeting to Clathrin-coated Pits* , 2000, The Journal of Biological Chemistry.

[19]  M. Sheng,et al.  Distinct molecular mechanisms and divergent endocytotic pathways of AMPA receptor internalization , 2000, Nature Neuroscience.

[20]  Stuart G. Cull-Candy,et al.  Synaptic activity at calcium-permeable AMPA receptors induces a switch in receptor subtype , 2000, Nature.

[21]  D. Lewis.  GABAergic local circuit neurons and prefrontal cortical dysfunction in schizophrenia , 2000, Brain Research Reviews.

[22]  M. Bear,et al.  Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity , 2000, Nature.

[23]  Z. Nusser.  AMPA amd NMDA receptors: similarities and differences in their synaptic distribution , 2000, Current Opinion in Neurobiology.

[24]  Yu Tian Wang,et al.  Regulation of AMPA Receptor–Mediated Synaptic Transmission by Clathrin-Dependent Receptor Internalization , 2000, Neuron.

[25]  D. Linden,et al.  Expression of Cerebellar Long-Term Depression Requires Postsynaptic Clathrin-Mediated Endocytosis , 2000, Neuron.

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

[27]  G. Collingridge,et al.  Developmental Changes in Synaptic AMPA and NMDA Receptor Distribution and AMPA Receptor Subunit Composition in Living Hippocampal Neurons , 2000, The Journal of Neuroscience.

[28]  Mark von Zastrow,et al.  Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD , 2000, Nature Neuroscience.

[29]  A. Triller,et al.  Fast and reversible trapping of surface glycine receptors by gephyrin , 2001, Nature Neuroscience.

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

[31]  Pasko Rakic,et al.  Telencephalic origin of human thalamic GABAergic neurons , 2001, Nature Neuroscience.

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

[33]  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.

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

[35]  J. Kiss,et al.  Contribution of the Neural Cell Adhesion Molecule to Neuronal and Synaptic Plasticity , 2001, Reviews in the neurosciences.

[36]  A. Sergé,et al.  Receptor Activation and Homer Differentially Control the Lateral Mobility of Metabotropic Glutamate Receptor 5 in the Neuronal Membrane , 2002, The Journal of Neuroscience.