Pathway-Specific Trafficking of Native AMPARs by In Vivo Experience

An accumulating body of evidence supports the notion that trafficking of AMPA receptors (AMPARs) underlies strengthening of glutamatergic synapses and, in turn, learning and memory in the behaving animal. However, without exception, these experiments have been performed using artificial stimulation protocols, cultured neurons, or viral-overexpression systems that can significantly alter the normal function of AMPARs. Using a single-whisker experience protocol that significantly enhances neuronal responses in vivo, we have targeted neurons in and around the spared whisker column of fosGFP transgenic mice for whole-cell recording. Here we show that in vivo experience induces the pathway-specific strengthening of neocortical excitatory synapses. By assaying AMPARs for rectification and sensitivity to joro spider toxin, we find that in vivo experience induces the delivery of native GluR2-lacking receptors at spared, but not deprived, inputs. These data demonstrate that pathway-specific trafficking of GluR2-lacking AMPARs is a normal feature of synaptic strengthening that underlies experience-dependent plasticity in the behaving animal.

[1]  D. Feldman,et al.  Long-term depression induced by sensory deprivation during cortical map plasticity in vivo , 2003, Nature Neuroscience.

[2]  Joseph E LeDoux,et al.  Postsynaptic Receptor Trafficking Underlying a Form of Associative Learning , 2005, Science.

[3]  J. Weiss,et al.  Heterogeneity of Ca2+-Permeable AMPA/Kainate Channel Expression in Hippocampal Pyramidal Neurons: Fluorescence Imaging and Immunocytochemical Assessment , 2003, The Journal of Neuroscience.

[4]  M A Xu-Friedman,et al.  Presynaptic strontium dynamics and synaptic transmission. , 1999, Biophysical journal.

[5]  J. Donoghue,et al.  Strengthening of horizontal cortical connections following skill learning , 1998, Nature Neuroscience.

[6]  T. Soderling,et al.  Ca2+/calmodulin-kinase II enhances channel conductance of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J. Lambert,et al.  Characteristics of AMPA receptor‐mediated responses of cultured cortical and spinal cord neurones and their correlation to the expression of glutamate receptor subunits, GluR1‐4 , 2001, British journal of pharmacology.

[8]  Michael Brecht,et al.  Map Plasticity in Somatosensory Cortex , 2005, Science.

[9]  R. Tsien,et al.  Adaptation to Synaptic Inactivity in Hippocampal Neurons , 2005, Neuron.

[10]  Mark J. Wall,et al.  The speeding of EPSC kinetics during maturation of a central synapse , 2002, The European journal of neuroscience.

[11]  T. Soderling,et al.  Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation. , 1997, Science.

[12]  Alison L. Barth,et al.  Upregulation of cAMP Response Element-Mediated Gene Expression during Experience-Dependent Plasticity in Adult Neocortex , 2000, The Journal of Neuroscience.

[13]  Mark J. Thomas,et al.  Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine , 2001, Nature Neuroscience.

[14]  K M Harris,et al.  Visualization of the Distribution of Autophosphorylated Calcium/Calmodulin-Dependent Protein Kinase II after Tetanic Stimulation in the CA1 Area of the Hippocampus , 1997, The Journal of Neuroscience.

[15]  R. Silver,et al.  Synaptic connections between layer 4 spiny neurone‐ layer 2/3 pyramidal cell pairs in juvenile rat barrel cortex: physiology and anatomy of interlaminar signalling within a cortical column , 2002, The Journal of physiology.

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

[17]  D. Wilkin,et al.  Neuron , 2001, Brain Research.

[18]  Tomoyuki Takahashi,et al.  Cellular/molecular Mechanisms Underlying Developmental Speeding in Ampa-epsc Decay Time at the Calyx of Held , 2022 .

[19]  Lu-Yang Wang,et al.  The Role of AMPA Receptor Gating in the Development of High-Fidelity Neurotransmission at the Calyx of Held Synapse , 2004, The Journal of Neuroscience.

[20]  B. Connors,et al.  Sensory experience modifies the short-term dynamics of neocortical synapses , 1999, Nature.

[21]  Gavin Rumbaugh,et al.  Phosphorylation of the AMPA Receptor GluR1 Subunit Is Required for Synaptic Plasticity and Retention of Spatial Memory , 2003, Cell.

[22]  V. Derkach,et al.  Dominant role of the GluR2 subunit in regulation of AMPA receptors by CaMKII , 2005, Nature Neuroscience.

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

[24]  B. Connors,et al.  Sensory deprivation without competition yields modest alterations of short-term synaptic dynamics. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[25]  S. Dudek,et al.  Pattern-Dependent Role of NMDA Receptors in Action Potential Generation: Consequences on Extracellular Signal-Regulated Kinase Activation , 2005, The Journal of Neuroscience.

[26]  Roberto Malinow,et al.  PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity , 2003, Nature Neuroscience.

[27]  M. McKERNAN,et al.  Fear conditioning induces a lasting potentiation of synaptic currents in vitro , 1997, Nature.

[28]  M. Bear,et al.  Molecular mechanism for loss of visual cortical responsiveness following brief monocular deprivation , 2003, Nature Neuroscience.

[29]  Richard C Gerkin,et al.  Alteration of Neuronal Firing Properties after In Vivo Experience in a FosGFP Transgenic Mouse , 2004, The Journal of Neuroscience.

[30]  R. Malenka,et al.  Differential Regulation of AMPA Receptor and GABA Receptor Trafficking by Tumor Necrosis Factor-α , 2005, The Journal of Neuroscience.

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

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

[33]  J. Zhu,et al.  Postnatal synaptic potentiation: Delivery of GluR4-containing AMPA receptors by spontaneous activity , 2000, Nature Neuroscience.

[34]  K. Fox,et al.  Time course of experience-dependent synaptic potentiation and depression in barrel cortex of adolescent rats. , 1996, Journal of neurophysiology.

[35]  R. Wenthold,et al.  Evidence for multiple AMPA receptor complexes in hippocampal CA1/CA2 neurons , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[36]  A. Schleicher,et al.  Expression of c-Fos, ICER, Krox-24 and JunB in the whisker-to-barrel pathway of rats: time course of induction upon whisker stimulation by tactile exploration of an enriched environment , 2002, Journal of Chemical Neuroanatomy.

[37]  M. Bear,et al.  Bidirectional, experience-dependent regulation of N-methyl-D-aspartate receptor subunit composition in the rat visual cortex during postnatal development. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[38]  H. Cline,et al.  Visually Driven Modulation of Glutamatergic Synaptic Transmission Is Mediated by the Regulation of Intracellular Polyamines , 2002, Neuron.

[39]  R. Huganir,et al.  Control of GluR1 AMPA Receptor Function by cAMP-Dependent Protein Kinase , 2000, The Journal of Neuroscience.

[40]  M. Bear,et al.  Visual Experience and Deprivation Bidirectionally Modify the Composition and Function of NMDA Receptors in Visual Cortex , 2001, Neuron.