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AMPA-Type Glutamate Receptor Conductance Changes and Plasticity: Still a Lot of Noise

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Abstract

Twenty years ago, we reported from the Collingridge Lab that a single-channel conductance increase through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type ionotropic glutamate receptors (AMPARs) could mediate one form of plasticity associated with long-term potentiation (LTP) in the hippocampus (Benke et al., Nature 395:793–797, 1998). Revealed through peak-scaled non-stationary fluctuation analysis (PS-NSFA, also known as noise analysis), this component of LTP could be exclusively mediated by direct increases in channel conductance or by increases in the number of high conductance synaptic AMPARs. Re-evaluation of our original data in the light of the molecular details regarding AMPARs, conductance changes and plasticity suggests that insertion of high-conductance GluA1 homomers can account for our initial findings. Any potential cost associated with manufacture or trafficking of new receptors could be mitigated if pre-existing synaptic AMPARs also undergo a modest conductance change. The literature suggests that the presence of high conductance AMPARs and/or GluA1 homomers confers an unstable synaptic state, suggesting state transitions. An experimental paradigm is proposed to differentiate these possibilities. Validation of this state diagram could provide insight into development, disease pathogenesis and treatment.

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References

  1. Greger IH, Watson JF, Cull-Candy SG (2017) Structural and functional architecture of AMPA-type glutamate receptors and their auxiliary proteins. Neuron 94:713–730

    Article  CAS  PubMed  Google Scholar 

  2. Lisman J (2017) Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: long-term potentiation, long-term depression, short-term potentiation and scaling. Philos Trans R Soc Lond B 372:20160260

    Article  CAS  Google Scholar 

  3. Hell JW (2016) How Ca2+-permeable AMPA receptors, the kinase PKA, and the phosphatase PP2B are intertwined in synaptic LTP and LTD. Sci Signal 9:pe2

    Article  CAS  Google Scholar 

  4. Herring BE, Nicoll RA (2016) Long-term potentiation: from CaMKII to AMPA receptor trafficking. Annu Rev Physiol 78:351–365

    Article  CAS  PubMed  Google Scholar 

  5. Traynelis SF, Silver RA, Cull-Candy SG (1993) Estimated conductance of glutamate receptor channels activated during EPSCs at the cerebellar mossy fiber-granule cell synapse. Neuron 11:279–289

    Article  CAS  PubMed  Google Scholar 

  6. Benke TA, Luthi A, Palmer MJ, Wikstrom M, Anderson WW, Isaac JTR, Collingridge GL (2001) Mathematical modeling of non-stationary fluctuation analysis for studying channel properties of synaptic AMPA receptors. J Physiol 537:2:407–420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Benke TA, Luthi A, Isaac JTR, Collingridge GL (1998) Modulation of AMPA receptor unitary conductance by synaptic activity. Nature 395:793–797

    Article  CAS  Google Scholar 

  8. Katz B, Miledi R (1972) The statistical nature of the acetycholine potential and its molecular components. J Physiol 224:665–699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Anderson CR, Stevens CF (1973) Voltage clamp analysis of acetylcholine produced end-plate current fluctuations at frog neuromuscular junction. J Physiol 235:655–691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sigworth FJ (1980) The variance of sodium current fluctuations at the node of Ranvier. J Physiol 307:97–129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Heinemann SH, Conti F (1992) Nonstationary noise analysis and application to patch clamp recordings. Methods Enzymol 207:131–148

    Article  CAS  PubMed  Google Scholar 

  12. Cull-Candy SG, Howe JR, Ogden DC (1988) Noise and single channels activated by excitatory amino acids in rat cerebellar granule neurones. J Physiol 400:189–222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Traynelis SF, Jaramillo F (1998) Getting the most out of noise in the central nervous system. Trends Neurosci 21:137–145

    Article  CAS  PubMed  Google Scholar 

  14. Matsuzaki M, Ellis-Davies GC, Nemoto T, Miyashita Y, Iino M, Kasai H (2001) Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons. Nat Neurosci 4:1086–1092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Poncer JC, Esteban JA, Malinowm R (2002) Multiple mechanisms for the potentiation of AMPA receptor-mediated transmission by alpha-Ca2+/calmodulin-dependent protein kinase II. J Neurosci 22:4406–4411

    Article  CAS  PubMed  Google Scholar 

  16. Guire ES, Oh MC, Soderling TR, Derkach VA (2008) Recruitment of calcium-permeable AMPA receptors during synaptic potentiation is regulated by CaM-kinase I. J Neurosci 28:6000–6009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Derkach V, Barria A, Soderling TR (1999) Ca2+/calmodulin-kinase II enhances channel conductance of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors. Proc Natl Acad Sci USA 96:3269–3274

    Article  CAS  PubMed  Google Scholar 

  18. Oh MC, Derkach VA (2005) Dominant role of the GluR2 subunit in regulation of AMPA receptors by CAMKII. Nat Neurosci 8:853–854

    Article  CAS  PubMed  Google Scholar 

  19. Swanson GT, Feldmeyer D, Kaneda M, Cull-Candy SG (1996) Effect of RNA editing and subunit co-assembly on single- channel properties of recombinant kainate receptors. J Physiol 492:129–142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Swanson GT, Kamboj SK, Cull-Candy SG (1997) Single-channel properties of recombinant AMPA receptors depend on RNA editing, splice variation, and subunit composition. J Neurosci 17:58–69

    Article  CAS  PubMed  Google Scholar 

  21. Kristensen AS, Jenkins MA, Banke TG, Schousboe A, Makino Y, Johnson RC, Huganir R, Traynelis SF (2011) Mechanism of Ca2+/calmodulin-dependent kinase II regulation of AMPA receptor gating. Nat Neurosci 14:727–735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Robinson HPC, Sahara Y, Kawai N (1991) Nonstationary fluctuation analysis and direct resolution of single channel currents at postsynaptic sites. Biophys J 59:295–304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. De Koninck Y, Mody I (1994) Noise analysis of miniature IPSCs in adult rat brain slices: properties and modulation of synaptic GABA A receptor channels. J Neurophysiol 71:1318–1335

    Article  PubMed  Google Scholar 

  24. Ling DS, Benardo LS, Sacktor TC (2006) Protein kinase Mzeta enhances excitatory synaptic transmission by increasing the number of active postsynaptic AMPA receptors. Hippocampus 16:443–452

    Article  CAS  PubMed  Google Scholar 

  25. Andrasfalvy BK, Magee JC (2004) Changes in AMPA receptor currents following LTP induction on rat CA1 pyramidal neurones. J Physiol 559:543–554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Luthi A, Palmer MJ, Anderson WW, Benke TA, Isaac JTR, Collingridge GL (2004) Bi-directional modulation of AMPA receptor unitary conductance by synaptic activity. BMC Neuroscience 5:44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Luthi A, Chittajallu R, Duprat F, Palmer MJ, Benke TA, Kidd FL, Henley JM, Isaac JTR, Collingridge GL (1999) Hippocampal LTD expression involves a pool of AMPARs regulated by the NSF-GluR2 interaction. Neuron 24:389–399

    Article  CAS  PubMed  Google Scholar 

  28. Palmer MJ, Isaac JTR, Collinridge GL (2004) Multiple, developmentally regulated expression mechanisms of long-term potentiation at CA1 synapses. J Neurosci 24:4903–4911

    Article  CAS  PubMed  Google Scholar 

  29. Lei S, Pelkey KA, Topolnik L, Congar P, Lacaille JC, McBain CJ (2003) Depolarization-induced long-term depression at hippocampal mossy fiber-CA3 pyramidal neuron synapses. J Neurosci 23:9786–9795

    Article  CAS  PubMed  Google Scholar 

  30. Bosman LW, Takechi H, Hartmann J, Eilers J, Konnerth A (2008) Homosynaptic long-term synaptic potentiation of the “winner” climbing fiber synapse in developing Purkinje cells. J Neurosci 28:798–807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Linden DJ (2001) The expression of cerebellar LTD in culture is not associated with changes in AMPA-receptor kinetics, agonist affinity, or unitary conductance. Proc Natl Acad Sci USA 98:14066–14071

    Article  CAS  PubMed  Google Scholar 

  32. Balland B, Lachamp P, Strube C, Kessler JP, Tell F (2006) Glutamatergic synapses in the rat nucleus tractus solitarii develop by direct insertion of calcium-impermeable AMPA receptors and without activation of NMDA receptors. J Physiol 574:245–261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cull-Candy SG, Usowicz MM (1987) Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons. Nature 325:525–528

    Article  CAS  PubMed  Google Scholar 

  34. Jonas P, Major G, Sakmann B (1993) Quantal components of unitary EPSCs at the mossy fibre synapse on CA3 pyramidal cells of rat hippocampus. J Physiol 472:615–663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Banke TG, Bowie D, Lee HK, Huganir RL, Schousboe A, Traynelis SF (2000) Control of GluR1 AMPA receptor function by cAMP-dependent protein kinase. J Neurosci 20:89–102

    Article  CAS  PubMed  Google Scholar 

  36. Gebhardt C, Cull-Candy SG (2006) Influence of agonist concentration on AMPA- and kainate channels in CA1 pyramidal cells in rat hippocampal slices. J Physiol 573:371–394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Jahr CE, Stevens CF (1987) Glutamate activates multiple single channel conductances in hippocampal neurons. Nature 325:522–525

    Article  CAS  PubMed  Google Scholar 

  38. Momiyama A, Silver RA, Hausser M, Notomi T, Wu Y, Shigemoto R, Cull-Candy SG (2003) The density of AMPA receptors activated by a transmitter quantum at the climbing fibre-Purkinje cell synapse in immature rats. J Physiol 549:75–92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Tanaka J, Matsuzaki M, Tarusawa E, Momiyama A, Molnar E, Kasai H, Shigemoto R (2005) Number and density of AMPA receptors in single synapses in immature cerebellum. J Neurosci 25:799–807

    Article  CAS  PubMed  Google Scholar 

  40. Wenthold RJ, Petralia RS, Blahos J II, Niedzielski AS AS (1996) Evidence for multiple AMPA receptor complexes in hippocampal CA1/CA2 neurons. J Neurosci 16:1982–1989

    Article  CAS  PubMed  Google Scholar 

  41. Lu W, Shi Y, Jackson AC, Bjorgan K, During MJ, Sprengel R, Seeburg PH, Nicoll RA (2009) Subunit composition of synaptic AMPA receptors revealed by a single-cell genetic approach. Neuron 62:254–268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Stubblefield EA, Benke TA (2010) Distinct AMPA-type glutamatergic synapses in developing rat CA1 hippocampus. J Neurophysiol 104:1899–1812

    Article  CAS  Google Scholar 

  43. Adesnik H, Nicoll RA (2007) Conservation of glutamate receptor 2-containing AMPA receptors during long-term potentiation. J Neurosci 27:4598–4602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Robertson HR, Gibson ES, Benke TA, Dell’Acqua ML (2009) Regulation of postsynaptic structure and function by an A-kinase anchoring protein-membrane-associated guanylate kinase scaffolding complex. J Neurosci 29:7929–7943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Mattison HA, Bagal AA, Mohammadi M, Pulimood NS, Reich CG, Alger BE, Kao JP, Thompson SM (2014) Evidence of calcium-permeable AMPA receptors in dendritic spines of CA1 pyramidal neurons. J Neurophysiol 112:263–275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Rozov A, Sprengel R, Seeburg PH (2012) GluA2-lacking AMPA receptors in hippocampal CA1 cell synapses: evidence from gene-targeted mice. Front Mol Neurosci 5:22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Granger AJ, Shi Y, Lu W, Cerpas M, Nicoll RA (2013) LTP requires a reserve pool of glutamate receptors independent of subunit type. Nature 493:495–500

    Article  CAS  PubMed  Google Scholar 

  48. Renner MC, Albers EH, Gutierrez-Castellanos N, Reinders NR, van Huijstee AN, Xiong H, Lodder TR, Kessels HW (2017) Synaptic plasticity through activation of GluA3-containing AMPA-receptors. eLife 6:1

    Article  Google Scholar 

  49. Clements JD, Lester RAJ, Tong G, Jahr CE, Westbrook G (1992) The time course of glutamate in the synaptic cleft. Science 258:1498–1501

    Article  CAS  PubMed  Google Scholar 

  50. Smith TC, Howe JR (2000) Concentration-dependent substate behavior of native AMPA receptors. Nat Neurosci 3:992–996

    Article  CAS  PubMed  Google Scholar 

  51. Smith TC, Wang LW, Howe JR (2000) Heterogeneous conductance levels of native AMPA receptors. J Neurosci 20:2073–2085

    Article  CAS  PubMed  Google Scholar 

  52. Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H, Myers SJ, Dingledine R (2010) Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev 62:405–496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Zhou Z, Liu A, Xia S, Leung C, Qi J, Meng Y, Xie W, Park P, Collingridge GL, Jia Z (2018) The C-terminal tails of endogenous GluA1 and GluA2 differentially contribute to hippocampal synaptic plasticity and learning. Nat Neurosci 21:50–62

    Article  CAS  PubMed  Google Scholar 

  54. Jenkins MA, Wells G, Bachman J, Snyder JP, Jenkins A, Huganir RL, Oswald RE, Traynelis SF (2014) Regulation of GluA1 alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor function by protein kinase C at serine-818 and threonine-840. Mol Pharmacol 85:618–629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Diering GH, Heo S, Hussain NK, Liu B, Huganir RL (2016) Extensive phosphorylation of AMPA receptors in neurons. Proc Natl Acad Sci USA 113:E4920-4927

    Article  CAS  Google Scholar 

  56. Lee HK, Kameyama K, Huganir RL, Bear MF (1998) NMDA induces long-term synaptic depression and dephosphorylation of the GluR1 subunit of AMPA receptors in hippocampus. Neuron 21:1151–1162

    Article  CAS  PubMed  Google Scholar 

  57. Kameyama K, Lee HK, Bear MF, Huganir RL (1998) Involvement of a postsynaptic protein kinase A substrate in the expression of homosynaptic long-term depression. Neuron 21:1163–1175

    Article  CAS  PubMed  Google Scholar 

  58. Sanderson JL, Gorski JA, Dell’Acqua ML (2016) NMDA receptor-dependent LTD Requires transient synaptic incorporation of Ca(2)(+)-permeable AMPARs mediated by AKAP150-anchored PKA and calcineurin. Neuron 89:1000–1015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Coultrap SJ, Freund RK, O’Leary H, Sanderson JL, Roche KW, Dell’Acqua ML, Bayer KU (2014) Autonomous CaMKII mediates both LTP and LTD using a mechanism for differential substrate site selection. Cell Rep 6:431–437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Selvakumar B, Jenkins MA, Hussain NK, Huganir RL, Traynelis SF, Snyder SH (2013) S-nitrosylation of AMPA receptor GluA1 regulates phosphorylation, single-channel conductance, and endocytosis. Proc Natl Acad Sci USA 110:1077–1082

    Article  PubMed  Google Scholar 

  61. Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39

    Article  CAS  PubMed  Google Scholar 

  62. Plant K, Pelkey KA, Bortolotto ZA, Morita D, Terashima A, McBain CJ, Collingridge GL, Isaac JTR (2006) Transient incorporation of native GluR2-lacking AMPA receptors during hippocampal long-term potentiation. Nat Neurosci 9:602–604

    Article  CAS  PubMed  Google Scholar 

  63. Isaac JT, Ashby MC, McBain CJ (2007) The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity. Neuron 54:859–871

    Article  CAS  PubMed  Google Scholar 

  64. Lu Y, Allen M, Halt AR, Weisenhaus M, Dallapiazza RF, Hall DD, Usachev YM, McKnight GS, Hell JW (2007) Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP. EMBO J 26:4879–4890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Park P, Sanderson TM, Amici M, Choi SL, Bortolotto ZA, Zhuo M, Kaang BK, Collingridge GL (2016) Calcium-permeable AMPA receptors mediate the induction of the protein kinase A-dependent component of long-term potentiation in the hippocampus. J Neurosci 36:622–631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Sinnen BL, Bowen AB, Forte JS, Hiester BG, Crosby KC, Gibson ES, Dell’Acqua ML, Kennedy MJ (2017) Optogenetic control of synaptic composition and function. Neuron 93:646–660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Noguchi J, Nagaoka A, Watanabe S, Ellis-Davies GC, Kitamura K, Kano M, Matsuzaki M, Kasai H (2011) In vivo two-photon uncaging of glutamate revealing the structure-function relationships of dendritic spines in the neocortex of adult mice. J Physiol 589:2447–2457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Hosokawa T, Rusakov DA, Bliss TVP, Fine A (1995) Repeated confocal imaging of individual dendritic spines in the living hippocampal slice: evidence for changes in length and orientation associated with chemically induced LTP. J Neurosci 15:5560–5573

    Article  CAS  PubMed  Google Scholar 

  69. Matsuzaki M, Ellis-Davies GCR, Nemoto T, Miyashita Y, Iino M, Kasai H (2001) Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons. Nat Neurosci 4:1086–1092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Matsuzaki M, Honkura N, Ellis-Davies GC, Kasai H (2004) Structural basis of long-term potentiation in single dendritic spines. Nature 429:761–766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Pi HJ, Otmakhov N, El Gaamouch F, Lemelin D, De Koninck P, Lisman J (2010) CaMKII control of spine size and synaptic strength: role of phosphorylation states and nonenzymatic action. Proc Natl Acad Sci USA 107:14437–14442

    Article  PubMed  Google Scholar 

  72. Isaac JTR, Nicoll RA, Malenka RC (1995) Evidence for silent synapses: implications for the expression of LTP. Neuron 15:427–434

    Article  CAS  PubMed  Google Scholar 

  73. Sanderson JL, Gorski JA, Gibson ES, Lam P, Freund RK, Chick WS, Dell’Acqua ML (2012) AKAP150-anchored calcineurin regulates synaptic plasticity by limiting synaptic incorporation of Ca2+-permeable AMPA receptors. J Neurosci 32:15036–15052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Lu Y, Zhang M, Lim IA, Hall DD, Allen M, Medvedeva Y, McKnight GS, Usachev YM, Hell JW (2008) AKAP150-anchored PKA activity is important for LTD during its induction phase. J Physiol 586:4155–4164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Harris KM, Jensen FE, Tsao B (1992) Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: implications for the maturation of synaptic physiology and long-term potentiation. J Neurosci 12:2685–2705

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The author appreciates the input provided by Drs. Dell’Acqua, Aoto, Bayer and Kennedy, their laboratories and Dr. Caballes and Ms. Castano in the Benke laboratory. Supported by NIH NS101288 and the Children’s Hospital Colorado Foundation (Ponzio Family Chair in Neurology Research) (Benke) and NIH NS036654 (Traynelis).

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  1. Departments of Pediatrics, Pharmacology, Neurology and Otolaryngology, University of Colorado, School of Medicine, Anschutz Medical Campus, Aurora, CO, USA

    Tim Benke

  2. Department of Pharmacology, Emory University School of Medicine, Atlanta, GA, USA

    Stephen F. Traynelis

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Correspondence to Tim Benke.

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Benke, T., Traynelis, S.F. AMPA-Type Glutamate Receptor Conductance Changes and Plasticity: Still a Lot of Noise. Neurochem Res 44, 539–548 (2019). https://doi.org/10.1007/s11064-018-2491-1

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