Abstract
Synaptic modification of transmission is a general phenomenon expressed at almost every excitatory synapse in the mammalian brain. Over the last three decades, much has been discovered about the cellular, synaptic, molecular, and signaling mechanisms responsible for controlling synaptic transmission and plasticity. Here, we present a brief review of these mechanisms with emphasis on the current understanding of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPA-R) trafficking and Ras-mitogen-activated protein kinase (MAPK) signaling events involved in controlling synaptic transmission.
Similar content being viewed by others
Article PDF
References
Bliss TV, Lomo T . Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol (Lond) 1973; 232: 331–56.
Bliss TV, Collingridge GL . A synaptic model of memory: long-term potentiation in the hippocampus. Nature 1993; 361: 31–9.
Malenka RC, Nicoll RA . Long-term potentiation — a decade of progress? Science 1999; 285: 1870–4.
Malinow R . AMPA receptor trafficking and long-term potentiation. Philos Trans R Soc Lond B Biol Sci 2003; 358: 707–14.
Malenka RC, Bear MF . LTP and LTD: an embarrassment of riches. Neuron 2004; 44: 5–21.
Thomas, GM, Huganir, RL . MAPK cascade signalling and synaptic plasticity. Nat Rev Neurosci 2004; 5: 173–83.
Collingridge GL, Isaac JT, Wang YT . Receptor trafficking and synaptic plasticity. Nat Rev Neurosci 2004; 5: 952–62.
Nicoll RA, Tomita S, Bredt DS . Auxiliary subunits assist AMPA-type glutamate receptors. Science 2006; 311: 1253–6.
Tada T, Sheng M . Molecular mechanisms of dendritic spine morphogenesis. Curr Opin Neurobiol 2006; 16: 95–101.
Manabe T, Wyllie DJ, Perkel DJ, Nicoll RA . Modulation of synaptic transmission and long-term potentiation: effects on paired pulse facilitation and EPSC variance in the CA1 region of the hippocampus. J Neurophysiol 1993; 70: 1451–9.
Liao D, Hessler NA, Malinow R . Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice. Nature 1995; 375: 400–4.
Isaac JT, Nicoll RA, Malenka RC . Evidence for silent synapses: implications for the expression of LTP. Neuron 1995; 15: 427–34.
Durand GM, Kovalchuk Y, Konnerth A . Long-term potentiation and functional synapse induction in developing hippocampus. Nature 1996; 381: 71–5.
Isaac JT, Crair MC, Nicoll RA, Malenka RC . Silent synapses during development of thalamocortical inputs. Neuron 1997; 18: 269–80.
Li P, Kerchner GA, Sala C, Wei F, Huettner JE, Sheng M, et al. AMPA receptor-PDZ interactions in facilitation of spinal sensory synapses. Nat Neurosci 1999; 2: 972–7.
Liao D, Zhang X, O'Brien R, Ehlers MD, Huganir RL . Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons. Nat Neurosci 1999; 2: 37–43.
Petralia RS, Esteban JA, Wang YX, Partridge JG, Zhao HM, Wenthold RJ, et al. Selective acquisition of AMPA receptors over postnatal development suggests a molecular basis for silent synapses. Nat Neurosci 1999; 2: 31–6.
Rosenmund C, Stern-Bach Y, Stevens CF . The tetrameric structure of a glutamate receptor channel. Science 1998; 280: 1596–9.
Greger IH, Khatri L, Kong X, Ziff EB . AMPA receptor tetramerization is mediated by Q/R editing. Neuron 2003; 40: 763–74.
Hollmann M, Heinemann S . Cloned glutamate receptors. Annu Rev Neurosci 1994; 17: 31–108.
Schoepfer R, Monyer H, Sommer B, Wisden W, Sprengel R, Kuner, T, et al. Molecular biology of glutamate receptors. Prog Neurobiol 1994; 42: 353–7.
Dingledine R, Borges K, Bowie D, Traynelis SF . The glutamate receptor ion channels. Pharmacol Rev 1999; 51: 7–61.
Shi SH, Hayashi Y, Petralia RS, Zaman SH, Wenthold RJ, Svoboda K, et al. Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science 1999; 284: 1811–6.
Malinow R, Malenka RC . AMPA receptor trafficking and synaptic plasticity. Annu Rev Neurosci 2002; 25: 103–26.
Zhu JJ, Esteban JA, Hayashi Y, Malinow R . Postnatal synaptic potentiation: delivery of G1uR4-containing AMPA receptors by spontaneous activity. Nat Neurosci 2000; 3: 1098–106.
Hayashi Y, Shi SH, Esteban JA, Piccini A, Poncer JC, Malinow R . Driving AMPA receptors into synapses by LTP and CaMKII: requirement for G1uR1 and PDZ domain interaction. Science 2000; 287: 2262–7.
Kolleker A, Zhu JJ, Schupp BJ, Qin Y, Mack V, Borchardt T, et al. Glutamatergic plasticity by synaptic delivery of G1uR-B (long)-containing AMPA receptors. Neuron 2003; 40: 1199–212.
Zhu JJ, Qin Y, Zhao M, Van Aelst L, Malinow R . Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell 2002; 110: 443–55.
Park M, Penick EC, Edwards JG, Kauer JA, Ehlers MD . Recycling endosomes supply AMPA receptors for LTP. Science 2004; 305: 1972–5.
Zhu JJ, Malinow R . Acute versus chronic NMDA receptor blockade and synaptic AMPA receptor delivery. Nat Neurosci 2002; 5: 513–4.
Shi S, Hayashi Y, Esteban JA, Malinow R . Subunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons. Cell 2001; 105: 331–43.
Takahashi T, Svoboda K, Malinow R . Experience strengthening transmission by driving AMPA receptors into synapses. Science 2003; 299: 1585–8.
Rumpel S, LeDoux J, Zador A, Malinow R . Postsynaptic receptor trafficking underlying a form of associative learning. Science 2005; 308: 83–8.
Qin Y, Zhu Y, Baumgart JP, Stornetta RL, Seidenman K, Mack V, et al. State-dependent Ras signaling and AMPA receptor trafficking. Genes Dev 2005; 19: 2000–15.
Malinow R, Mainen ZF, Hayashi Y . LTP mechanisms: from silence to four-lane traffic. Curr Opin Neurobiol 2000; 10: 352–7.
McCormack SG, Stornetta RL, Zhu JJ . Synaptic AMPA receptor exchange maintains bidirectional plasticity. Neuron 2006; 50: 75–88.
Zhu Y, Pak D, Qin Y, McCormack SG, Kim MJ, Baumgart JP, et al. Rap2-JNK removes synaptic AMPA receptors during depotentiation. Neuron 2005; 46: 905–16.
Nishimune A, Isaac JT, Molnar E, Noel J, Nash SR, Tagaya M, et al. NSF binding to G1uR2 regulates synaptic transmission. Neuron 1998; 21: 87–97.
Osten P, Srivastava S, Inman GJ, Vilim FS, Khatri L, Lee LM, et al. The AMPA receptor G1uR2 C terminus can mediate a reversible, ATP- dependent interaction with NSF and alpha- and beta-SNAPs. Neuron 1998; 21: 99–110.
Song I, Kamboj S, Xia J, Dong H, Liao D, Huganir RL . Interaction of the N-ethylmaleimide-sensitive factor with AMPA receptors. Neuron 1998; 21: 393–400.
Luscher C, Xia H, Beattie EC, Carroll RC, von Zastrow M, Malenka RC, et al. Role of AMPA receptor cycling in synaptic transmission and plasticity. Neuron 1999; 24: 649–58.
Lee SH, Liu L, Wang YT, Sheng M . Clathrin adaptor AP2 and NSF interact with overlapping sites of G1uR2 and play distinct roles in AMPA receptor trafficking and hippocampal LTD. Neuron 2002; 36: 661–74.
Adesnik H, Nicoll RA, England PM . Photoinactivation of native AMPA receptors reveals their real-time trafficking. Neuron 2005; 48: 977–85.
Chung HJ, Steinberg JP, Huganir RL, Linden DJ . Requirement of AMPA receptor G1uR2 phosphorylation for cerebellar long-term depression. Science 2003; 300: 1751–5.
Meng Y, Zhang Y, Jia Z . Synaptic transmission and plasticity in the absence of AMPA glutamate receptor G1uR2 and G1uR3. Neurone 2003; 39: 163–76.
Seidenman KJ, Steinberg JP, Huganir R, Malinow R . Glutamate receptor subunit 2 serine 880 phosphorylation modulates synaptic transmission and mediates plasticity in CA1 pyramidal cells. J Neurosci 2003; 23: 9220–8.
Beattie EC, Carroll RC, Yu X, Morishita W, Yasuda H, von Zastrow M, et al. Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD. Nat Neurosci 2000; 3: 1291–300.
Wang YT, Linden DJ . Expression of cerebellar long-term depression requires postsynaptic clathrin-mediated endocytosis. Neuron 2000; 25: 635–47.
Lee SH, Simonetta A, Sheng M . Subunit rules governing the sorting of internalized AMPA receptors in hippocampal neurons. Neuron 2004; 43: 221–36.
Brown TC, Tran IC, Backos DS, Esteban JA . NMDA receptor-dependentactivation of the small GTPase Rab5 drives the removal of synaptic AMPA receptors during hippocampal LTD. Neuron 2005; 45: 81–94.
Cull-Candy S, Kelly L, Farrant M . Regulation of Ca(2+)-permeable AMPA receptors: synaptic plasticity and beyond. Curr Opin Neurobiol 2006; 16: 288–97.
Clem RL, Barth A . Pathway-specific trafficking of native AMPARs by in vivo experience. Neuron 2006; 49: 663–70.
Bellone C, Luscher C . Cocaine triggered AMPA receptor redistribution is reversed in vivo by mG1uR-dependent long-term depression. Nat Neurosci 2006; 9: 636–41.
Kumar SS, Huguenard JR . Pathway-specific differences in sub-unit composition of synaptic NMDA receptors on pyramidal neurons in neocortex. J Neurosci 2003; 23: 10 074–83.
Gardner SM, Takamiya K, Xia J, Suh JG, Johnson R, Yu S, et al. Calcium-permeable AMPA receptor plasticity is mediated by subunit-specific interactions with PICK1 and NSF. Neuron 2005; 45: 903–15.
Liu SJ, Cull-Candy SG . Subunit interaction with PICK and GRIP controls Ca2+ permeability of AMPARs at cerebellar synapses. Nat Neurosci 2005; 8: 768–75.
Bagal AA, Kao JP, Tang CM, Thompson SM . Long-term potentiation of exogenous glutamate responses at single dendritic spines. Proc Natl Acad Sci USA 2005; 102: 14434–9.
Plant K, Pelkey KA, Bortolotto ZA, Morita D, Terashima A, McBain CJ, et al. Transient incorporation of native GluR2-lacking AMPA receptors during hippocampal long-term potentiation. Nat Neurosci 2006; 9: 602–4.
Liu S, Lau L, Wei J, Zhu D, Zou S, Sun HS, et al. Expression of Ca(2+)-permeable AMPA receptor channels primes cell death in transient forebrain ischemia. Neuron 2004; 43: 43–55.
Lai C, Xie C, McCormack SG, Chiang HC, Michalak MK, Lin X, et al. Amyotrophic lateral sclerosis 2-deficiency leads to neuronal degeneration in amyotrophic lateral sclerosis through altered AMPA receptor trafficking. J Neurosci 2006; 26: 11798–806.
Liu B, Liao M, Mielke JG, Ning K, Chen Y, Li L, et al. Ischemic insults direct glutamate receptor subunit 2-lacking AMPA receptors to synaptic sites. J Neurosci 2006; 26: 5309–19.
Takai Y, Sasaki T, Matozaki T . Small GTP-binding proteins. Physiol Rev 2001; 81: 153–208.
Kyriakis JM, Avruch J . Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 2001; 81: 807–69.
Vivanco I, Sawyers CL . The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer 2002; 2: 489–501.
Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SG . Proteomic analysis of NMDA receptor-adhesion protein signaling complexes. Nat Neurosci 2000; 3: 661–9.
Miyakawa T, Leiter LM, Gerber DJ, Gainetdinov RR, Sotnikova TD, Zeng H, et al. Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia. Proc Natl Acad Sci USA 2003; 100: 8987–92.
Comings DE, Wu S, Chiu C, Muhleman D, Sverd J . Studies of the c-Harvey-Ras gene in psychiatric disorders. Psychiatry Res 1996; 63: 25–32.
Savage MJ, Lin YG, Ciallella JR, Flood DG, Scott RW . Activation of c-Jun N-terminal kinase and p38 in an Alzheimer's disease model is associated with amyloid deposition. J Neurosci 2002; 22: 3376–85.
Marques CA, Keil U, Bonert A, Steiner B, Haass C, Muller WE, et al. Neurotoxic mechanisms caused by the Alzheimer's diseaselinked swedish APP mutation: oxidative stress, caspases and JNK pathway. J Biol Chem 2003; 278: 28 294–302.
Niihori T, Aoki Y, Narumi Y, Neri G, Cave H, Verloes A, et al. Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nat Genet 2006; 38: 294–6.
Costa RM, Federov NB, Kogan JH, Murphy GG, Stern J, Ohno M, et al. Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature 2002; 415: 526–30.
Tong J, Hannan F, Zhu Y, Bernards A, Zhong Y . Neurofibromin regulates G protein-stimulated adenylyl cyclase activity. Nat Neurosci 2002; 5: 95–6.
Inoki K, Zhu T, Guan KL . TSC2 mediates cellular energy response to control cell growth and survival. Cell 2003; 115: 577–90.
Yntema HG, van den Helm B, Kissing J, van Duijnhoven G, Poppelaars F, Chelly J, et al. A novel ribosomal S6-kinase (RSK4; RPS6KA6) is commonly deleted in patients with complex X-linked mental retardation. Genomics 1999; 62: 332–43.
Trivier E, De Cesare D, Jacquot S, Pannetier S, Zackai E, Young I, et al. Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome. Nature 1996; 384: 567–70.
English JD, Sweatt JD . A requirement for the mitogen-activated protein kinase cascade in hippocampal long term potentiation. J Biol Chem 1997; 272: 19 103–6.
Yasuda H, Barth AL, Stellwagen D, Malenka RC . A developmental switch in the signaling cascades for LTP induction. Nat Neurosci 2003; 6: 15–6.
Tian X, Gotoh T, Tsuji K, Lo EH, Huang S, Feig LA . Developmentally regulated role for Ras-GRFs in coupling NMDA glutamate receptors to Ras, Erk and CREB. EMBO J 2004; 23: 1567–75.
Esteban JA, Shi SH, Wilson C, Nuriya M, Huganir RL, Malinow R . PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity. Nat Neurosci 2003; 6: 136–43.
Blackstone C, Murphy TH, Moss SJ, Baraban JM, Huganir RL . Cyclic AMP and synaptic activity-dependent phosphorylation of AMPA- preferring glutamate receptors. J Neurosci 1994; 14: 7585–93.
Mammen AL, Kameyama K, Roche KW, Huganir RL . Phosphorylation of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit by calcium/calmodulindependent kinase II. J Biol Chem 1997; 272: 32 528–33.
Thomas GM, Rumbaugh GR, Harrar DB, Huganir RL . Ribosomal S6 kinase 2 interacts with and phosphorylates PDZ domain-containing proteins and regulates AMPA receptor transmission. Proc Natl Acad Sci USA 2005; 102: 15 006–11.
Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J . Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr Biol 2003; 13: 1259–68.
Tang SJ, Reis G, Kang H, Gingras AC, Sonenberg N, Schuman EM . A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus. Proc Natl Acad Sci USA 2002; 99: 467–72.
Mulkey RM, Herron CE, Malenka RC . An essential role for protein phosphatases in hippocampal long-term depression. Science 1993; 261: 1051–5.
Zhuo M, Zhang W, Son H, Mansuy I, Sobel RA, Seidman J, et al. A selective role of calcineurin aalpha in synaptic depotentiation in hippocampus. Proc Natl Acad Sci USA 1999; 96: 4650–5.
Malleret G, Haditsch U, Genoux D, Jones MW, Bliss TV, Vanhoose AM, et al. Inducible and reversible enhancement of learning, memory, and long-term potentiation by genetic inhibition of calcineurin. Cell 2001; 104: 675–86.
Chung HJ, Xia J, Scannevin RH, Zhang X, Huganir RL . Phosphorylation of the AMPA receptor subunit GluR2 differentially regulates its interaction with PDZ domain-containing proteins. J Neurosci 2000; 20: 7258–67.
Xia J, Chung HJ, Wihler C, Huganir RL, Linden DJ . Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins. Neuron 2000; 28: 499–510.
Srivastava S, Osten P, Vilim FS, Khatri L, Inman G, States B, et al. Novel anchorage of GluR2/3 to the postsynaptic density by the AMPA receptor-binding protein ABP. Neuron 1998; 21: 581–91.
Xia J, Zhang X, Staudinger J, Huganir RL . Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1. Neuron 1999; 22: 179–87.
Daw MI, Chittajallu R, Bortolotto ZA, Dev KK, Duprat F, Henley JM, et al. PDZ proteins interacting with C-terminal GluR2/3 are involved in a PKC-dependent regulation of AMPA receptors at hippocampal synapses. Neuron 2000; 28: 873–86.
Osten P, Khatri L, Perez JL, Köhr G, Giese G, Daly C, et al. Mutagenesis reveals a role for ABP/GRIP binding to GluR2 in synaptic surface accumulation of the AMPA receptor. Neuron 2000; 27: 313–25.
Kim CH, Chung HJ, Lee HK, Huganir RL . Interaction of the AMPA receptor subunit GluR2/3 with PDZ domains regulates hippocampal long-term depression. Proc Natl Acad Sci USA 2001; 98: 11 725–30.
Hirbec H, Francis JC, Lauri SE, Braithwaite SP, Coussen F, Mulle C, et al. Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP. Neuron 2003; 37: 625–38.
Jin W, Ge WP, Xu J, Cao M, Peng L, Yung W, et al. Lipid binding regulates synaptic targeting of PICK1, AMPA receptor trafficking, and synaptic plasticity. J Neurosci 2006; 26: 2380–90.
Gallo KA, Johnson GL . Mixed-lineage kinase control of JNK and p38 MAPK pathways. Nat Rev Mol Cell Biol 2002; 3: 663–72.
Asaki C, Usuda N, Nakazawa A, Kametani K, Suzuki T . Localization of translational components at the ultramicroscopic level at postsynaptic sites of the rat brain. Brain Res 2003; 972: 168–76.
Zhu JJ, Connors BW . Intrinsic firing patterns and whiskerevoked synaptic responses of neurons in the rat barrel cortex. J Neurophysiol 1999; 81: 1171–83.
Larkum ME, Zhu JJ . Signaling of layer 1 and whisker-evoked Ca2+ and Na+ action potentials in distal and terminal dendrites of rat neocortical pyramidal neurons in vitro and in vivo. J Neurosci 2002; 22: 6991–7005.
Margrie TW, Brecht M, Sakmann B . In vivo, low-resistance, whole-cell recordings from neurons in the anaesthetized and awake mammalian brain. Pflugers Arch 2002; 444: 491–8.
Zhu Y, Stornetta RL, Zhu JJ . Chandelier cells control excessive cortical excitation: characteristics of whisker-evoked synaptic responses of layer 2/3 nonpyramidal and pyramidal neurons. J Neurosci 2004; 24: 5101–8.
Lee AK, Manns ID, Sakmann B, Brecht M . Whole-cell recordings in freely moving rats. Neuron 2006; 51: 399–407.
Helmchen F, Fee MS, Tank DW, Denk W . A miniature headmounted two-photon microscope. High-resolution brain imaging in freely moving animals. Neuron 2001; 31: 903–12.
Yasuda R, Harvey CD, Zhong H, Sobczyk A, van Aelst L, Svoboda K . Supersensitive Ras activation in dendrites and spines revealed by two-photon fluorescence lifetime imaging. Nat Neurosci 2006; 9: 283–91.
Rubio ME, Wenthold RJ . Glutamate receptors are selectively targeted to postsynaptic sites in neurons. Neuron 1997; 18: 939–50.
Matsuzaki M, Honkura N, Ellis-Davies GC, Kasai H . Structural basis of long-term potentiation in single dendritic spines. Nature 2004; 429: 761–6.
Horton AC, Racz B, Monson EE, Lin AL, Weinberg RJ, Ehlers MD . Polarized secretory trafficking directs cargo for asymmetric dendrite growth and morphogenesis. Neuron 2005; 48: 757–71.
Kopec CD, Li B, Wei W, Boehm J, Malinow R . Glutamate receptor exocytosis and spine enlargement during chemically induced long-term potentiation. J Neurosci 2006; 26: 2000–9.
Park M, Salgado JM, Ostroff L, Helton TD, Robinson CG, Harris KM, et al. Plasticity-induced growth of dendritic spines by exocytic trafficking from recycling endosomes. Neuron 2006; 52: 817–30.
Komai S, Licznerski P, Cetin A, Waters J, Denk W, Brecht M, et al. Postsynaptic excitability is necessary for strengthening of cort ical sensory responses during experience-dependent development. Nat Neurosci 2006; 9: 1125–33.
Author information
Authors and Affiliations
Corresponding author
Additional information
Work from Julius ZHU Laboratory is supported in part by the US Department of Defense and National Institutes of Health USA.
Rights and permissions
About this article
Cite this article
Gu, Y., Stornetta, R. Synaptic plasticity, AMPA-R trafficking, and Ras-MAPK signaling. Acta Pharmacol Sin 28, 928–936 (2007). https://doi.org/10.1111/j.1745-7254.2007.00609.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2007.00609.x