The sequence of events that underlie quantal transmission at central glutamatergic synapses

Nature Reviews Neuroscience

Volumn 8, Issue 8, 2007, Pages 597-609

  Lisman, John E ^a   Raghavachari, Sridhar ^b   Tsien, Richard W ^c  

^a BRANDEIS UNIVERSITY   (United States)

^b DUKE UNIVERSITY MEDICAL CENTER   (United States)

^c STANFORD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA AMINO 3 HYDROXY 5 METHYL 4 ISOXAZOLEPROPIONIC ACID; AMINO ACID; CALCIUM CHANNEL; CALCIUM ION; GLUTAMIC ACID; NEUROTRANSMITTER; POSTSYNAPTIC RECEPTOR; SYNAPTOTAGMIN;

CALCIUM SIGNALING; CELL MEMBRANE CONDUCTANCE; CHANNEL GATING; DIFFUSION; HUMAN; LONG TERM POTENTIATION; MOLECULAR SENSOR; NERVE CELL PLASTICITY; NERVE ENDING; NEUROMUSCULAR SYNAPSE; NEUROTRANSMITTER RELEASE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; SYNAPSE VESICLE; SYNAPTIC TRANSMISSION;

ANIMALS; BRAIN; CALCIUM SIGNALING; GLUTAMIC ACID; HUMANS; MEMBRANE FUSION; RECEPTORS, AMPA; SYNAPSES; SYNAPTIC MEMBRANES; SYNAPTIC TRANSMISSION; SYNAPTIC VESICLES;

EID: 34447625042     PISSN: 1471003X     EISSN: 14710048     Source Type: Journal    
DOI: 10.1038/nrn2191     Document Type: Review

References (179)

1. Katz, B. Neural transmitter release: from quantal secretion to exocytosis and beyond. The Fenn Lecture. J. Neurocytol. 25, 677-686 (1996).
2. Heuser, J. E. et al. Synaptic vesicle exocytosis captured by quick freezing and correlated with quantal transmitter release. J. Cell Biol. 81, 275-300 (1979).
3. Heuser, J. E. & Reese, T. S. Structural changes after transmitter release at the frog neuromuscular junction. J. Cell Biol. 88, 564-580 (1981).
4. Stiles, J. R., Van Helden, D., Bartol, T. M. Jr, Salpeter, E. E. & Salpeter, M. M. Miniature endplate current rise times less than 100 microseconds from improved dual recordings can be modeled with passive acetylcholine diffusion from a synaptic vesicle. Proc. Natl Acad. Sci. USA 93, 5747-5752 (1996).
5. Borst, J. G., Helmchen, F. & Sakmann, B. Pre- and postsynaptic whole-cell recordings in the medial nucleus of the trapezoid body of the rat. J. Physiol. 489, 825-840 (1995).
6. + channels in hippocampal mossy fiber boutons. Neuron 28, 927-939 (2000).
7. Llinas, R., Steinberg, I. Z. & Walton, K. Relationship between presynaptic calcium current and postsynaptic potential in squid giant synapse. Biophys. J. 33, 323-351 (1981).
8. Augustine, G. J., Charlton, M. P. & Smith, S. J. Calcium entry and transmitter release at voltage-clamped nerve terminals of squid. J. Physiol. 367, 163-181 (1985).
9. Wu, L. G., Westenbroek, R. E., Borst, J. G., Catterall, W. A. & Sakmann, B. Calcium channel types with distinct presynaptic localization couple differentially to transmitter release in single calyx-type synapses. J. Neurosci. 19, 726-736 (1999).
10. Iwasaki, S., Momiyama, A., Uchitel, O. D. & Takahashi, T. Developmental changes in calcium channel types mediating central synaptic transmission. J. Neurosci. 20, 59-65 (2000).
11. 2+ channels: a functional patchwork. Trends Neurosci. 26, 683-687 (2003).
12. Momiyama, A. & Takahashi, T. Development of inhibitory synaptic currents in rat spinal neurons. Ann. NY Acad. Sci. 707, 447-448 (1993).
13. Mintz, I. M., Sabatini, B. L. & Regehr, W. G. Calcium control of transmitter release at a cerebellar synapse. Neuron 15, 675-688 (1995).
14. Sabatini, B. L. & Regehr, W. G. Timing of neurotransmission at fast synapses in the mammalian brain. Nature 384, 170-172 (1996). A study that provides a different view of the timing of steps leading to vesicle release. This study suggests that release can occur before the falling phase of the action potenital, making a much shorter synaptic delay possible.
15. Sabatini, B. L. & Regehr, W. G. Timing of synaptic transmission. Annu. Rev. Physiol. 61, 521-542 (1999).
16. McDonough, S. I., Mintz, I. M. & Bean, B. P. Alteration of P-type calcium channel gating by the spider toxin ω-Aga-IVA. Biophys. J. 72, 2117-2128 (1997).
17. Llinas, R., Sugimori, M. & Silver, R. B. Microdomains of high calcium concentration in a presynaptic terminal. Science 256, 677-679 (1992).
18. Serulle, Y., Sugimori, M. & Llinas, R. R. Imaging synaptosomal calcium concentration microdomains and vesicle fusion by using total internal reflection fluorescent microscopy. Proc. Natl Acad. Sci. USA 104, 1697-1702 (2007).
19. Stanley, E. F. The calcium channel and the organization of the presynaptic transmitter release face. Trends Neurosci. 20, 404-409 (1997).
20. Harlow, M. L., Ress, D., Stoschek, A., Marshall, R. M. & McMahan, U. J. The architecture of active zone material at the frog's neuromuscular junction. Nature 409, 479-484 (2001).
21. Pumplin, D. W., Reese, T. S. & Llinás, R. Are the presynaptic membrane particles the calcium channels? Proc. Natl Acad. Sci. USA 78, 7210-7213 (1981).
22. 2+ from one or two channels controls fusion of a single vesicle at the frog neuromuscular junction. J. Neurosci. 26, 13240-13249 (2006).
23. Ohana, O. & Sakmann, B. Transmitter release modulation in nerve terminals of rat neocortical pyramidal cells by intracellular calcium buffers. J. Physiol. 513, 135-148 (1998).
24. 2+ buffers and synaptic efficacy. Cell Calcium 37, 489-495 (2005).
25. 2+ changes in the presynaptic terminal.
26. Bollmann, J. H., Sakmann, B. & Borst, J. G. Calcium sensitivity of glutamate release in a calyx-type terminal. Science 289, 953-957 (2000).
27. 2+ elevation produced by an action potential and to study the resulting transmitter release.
28. Bennett, M. K., Calakos, N. & Scheller, R. H. Syntaxin: a synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science 257, 255-259 (1992).
29. Sheng, Z. H., Rettig, J., Cook, T. & Catterall, W. A. Calcium-dependent interaction of N-type calcium channels with the synaptic core complex. Nature 379, 451-454 (1996).
30. Jarvis, S. E. & Zamponi, G. W. Masters or slaves? Vesicle release machinery and the regulation of presynaptic calcium channels. Cell Calcium 37, 483-488 (2005).
31. 2+ signal for phasic transmitter release at the rat calyx of Held. J. Physiol. 547, 665-689 (2003).
32. Meinrenken, C. J., Borst, J. G. & Sakmann, B. Calcium secretion coupling at calyx of held governed by nonuniform channel-vesicle topography. J. Neurosci. 22, 1648-1667 (2002).
33. 2+ channels determines fast neurotransmitter release. Neuron 53, 563-575 (2007).
34. Fedchyshyn, M. J. & Wang, L. Y. Developmental transformation of the release modality at the calyx of Held synapse. J. Neurosci. 25, 4131-4140 (2005).
35. Zhai, R. G. & Bellen, H. J. The architecture of the active zone in the presynaptic nerve terminal. Physiology (Bethesda) 19, 262-270 (2004).
36. Zampighi, G. A. et al. Conical electron tomography of a chemical synapse: vesicles docked to the active zone are hemi-fused. Biophys. J. 91, 2910-2918 (2006).
37. Phillips, G. R. et al. The presynaptic particle web: ultrastructure, composition, dissolution, and reconstitution. Neuron 32, 63-77 (2001).
38. 2+-dependent and lacks a direct influence of presynaptic membrane potential. Proc. Natl Acad. Sci. USA 100, 15200-15205 (2003).
39. Dodge, F. A. Jr & Rahamimoff, R. Co-operative action of calcium ions in transmitter release at the neuromuscular junction. J. Physiol. 193, 419-432 (1967).
40. 2+ sensitivity of vesicle pool depletion at a fast CNS synapse. J. Neurosci. 23, 7059-7068 (2003).
41. Zucker, R. S. & Regehr, W. G. Short-term synaptic plasticity. Annu. Rev. Physiol. 64, 355-405 (2002).
42. Bischofberger, J., Engel, D., Frotscher, M. & Jonas, P. Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network. Pflugers Arch. 453, 361-372 (2006).
43. 2+ requirements and developmental regulation of posttetanic potentiation at the calyx of Held. J. Neurosci. 25, 5127-5137 (2005).
44. Isaacson, J. S. & Walmsley, B. Counting quanta: direct measurements of transmitter release at a central synapse. Neuron 15, 875-884 (1995).
45. Diamond, J. S. & Jahr, C. E. Asynchronous release of synaptic vesicles determines the time course of the AMPA receptor-mediated EPSC. Neuron 15, 1097-1107 (1995).
46. Millet, O., Bernado, P., Garcia, J., Rizo, J. & Pons, M. NMR measurement of the off rate from the first calcium-binding site of the synaptotagmin I C2A domain. FEBS Lett. 516, 93-96 (2002).
47. 2+ signaling. J. Neurosci. 25, 96-107 (2005).
48. Sudhof, T. C. The synaptic vesicle cycle. Annu. Rev. Neurosci. 27, 509-547 (2004).
49. 2+ sensor for transmitter release at a central synapse. Cell 79, 717-727 (1994).
50. 2+-dependent neurotransmitter release. J. Neurosci. 24, 8542-8550 (2004).
51. Nishiki, T. & Augustine, G. J. Synaptotagmin I synchronizes transmitter release in mouse hippocampal neurons. J. Neurosci. 24, 6127-6132 (2004).
52. Fernandez-Chacon, R. et al. Synaptotagmin I functions as a calcium regulator of release probability. Nature 410, 41-49 (2001).
53. Takamori, S. et al. Molecular anatomy of a trafficking organelle. Cell 127, 831-846 (2006).
54. Stewart, B. A., Mohtashami, M., Trimble, W. S. & Boulianne, G. L. SNARE proteins contribute to calcium cooperativity of synaptic transmission. Proc. Natl Acad. Sci. USA 97, 13955-13960 (2000).
55. Hua, Y. & Scheller, R. H. Three SNARE complexes cooperate to mediate membrane fusion. Proc. Natl Acad. Sci. USA 98, 8065-8070 (2001).
56. Montecucco, C., Schiavo, G. & Pantano, S. SNARE complexes and neuroexocytosis: how many, how close? Trends Biochem. Sci. 30, 367-372 (2005).
57. Xu, Y., Zhang, F., Su, Z., McNew, J. A. & Shin, Y. K. Hemifusion in SNARE-mediated membrane fusion. Nature Struct. Mol. Biol. 12, 417-422 (2005).
58. Reese, C., Heise, F. & Mayer, A. Trans-SNARE pairing can precede a hemifusion intermediate in intracellular membrane fusion. Nature 436, 410-414 (2005).
59. Giraudo, C. G., Eng, W. S., Melia, T. J. & Rothman, J. E. A clamping mechanism involved in SNARE-dependent exocytosis. Science 313, 676-680 (2006).
60. Tang, J. et al. A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis. Cell 126, 1175-1187 (2006). This paper provides insights into the steps that make the vesicle primed for release.
61. 2+-synaptotagmin I. Nature Struct. Mol. Biol. 13, 748-750 (2006). Direct measurements of membrane mixing provide unique insights into the fusion process.
62. Zimmerberg, J., Akimov, S. A. & Frolov, V. Synaptotagmin: fusogenic role for calcium sensor? Nature Struct. Mol. Biol. 13, 301-303 (2006).
63. 2+-triggered exocytosis. Annu. Rev. Biophys. Biomol. Struct. 35, 135-160 (2006). An excellent review of the issues regarding the mechanism by which the fusion pore is generated.
64. 2+-triggered exocytosis. Science 304, 289-292 (2004).
65. Han, X. & Jackson, M. B. Electrostatic interactions between the syntaxin membrane anchor and neurotransmitter passing through the fusion pore. Biophys. J. 88, L20-L22 (2005).
66. Almers, W. Exocytosis. Annu. Rev. Physiol. 52, 607-624 (1990).
67. He, L., Wu, X. S., Mohan, R. & Wu, L. G. Two modes of fusion pore opening revealed by cell-attached recordings at a synapse. Nature 444, 102-105 (2006). A technical breakthrough allows direct measurements of vesicle fusion and fusion pore formation at the secretory face of a central synapse.
68. Chen, X., Wang, L., Zhou, Y., Zheng, L. H. & Zhou, Z. 'Kiss-and-run' glutamate secretion in cultured and freshly isolated rat hippocampal astrocytes. J. Neurosci. 25, 9236-9243 (2005).
69. Klyachko, V. A. & Jackson, M. B. Capacitance steps and fusion pores of small and large-dense-core vesicles in nerve terminals. Nature 418, 89-92 (2002).
70. Harata, N. C., Aravanis, A. M. & Tsien, R. W. Kiss-and-run and full-collapse fusion as modes of exoendocytosis in neurosecretion. J. Neurochem. 97, 1546-1570 (2006).
71. Harata, N. C., Choi, S., Pyle, J. L., Aravanis, A. M. & Tsien, R. W. Frequency-dependent kinetics and prevalence of kiss-and-run and reuse at hippocampal synapses studied with novel quenching methods. Neuron 49, 243-256 (2006).
72. Aravanis, A. M., Pyle, J. L. & Tsien, R. W. Single synaptic vesicles fusing transiently and successively without loss of identity. Nature 423, 643-647 (2003).
73. Ceccarelli, B., Hurlbut, W. P. & Mauro, A. Turnover of transmitter and synaptic vesicles at the frog neuromuscular junction. J. Cell Biol. 57, 499-524 (1973).
74. Gandhi, S. P. & Stevens, C. F. Three modes of synaptic vesicular recycling revealed by single-vesicle imaging. Nature 423, 607-613 (2003).
75. Pawlu, C., DiAntonio, A. & Heckmann, M. Postfusional control of quantal current shape. Neuron 42, 607-618 (2004).
76. Burger, P. M. et al. Synaptic vesicles immunoisolated from rat cerebral cortex contain high levels of glutamate. Neuron 3, 715-720 (1989).
77. Raghavachari, S. & Lisman, J. E. Properties of quantal transmission at CA1 synapses. J. Neurophysiol. 92, 2456-2467 (2004). This paper used Monte-Carlo simulations to show how the glutamate released from a vesicle diffuses in the cleft and activates AMPA channels.
78. Tanaka, J. et al. Number and density of AMPA receptors in single synapses in immature cerebellum. J. Neurosci. 25, 799-807 (2005).
79. Nielsen, T. A., DiGregorio, D. A. & Silver, R. A. Modulation of glutamate mobility reveals the mechanism underlying slow-rising AMPAR EPSCs and the diffusion coefficient in the synaptic cleft. Neuron 42, 757-771 (2004). This paper uses a clever combination of experimental manipulation and modelling to discern the diffusion coefficient of the neurotransmitter glutamate in the synpaptic cleft. This is an important parameter in determining the amplitude of synaptic responses.
80. Smith, M. A., Ellis-Davies, G. C. & Magee, J. C. Mechanism of the distance-dependent scaling of Schaffer collateral synapses in rat CA1 pyramidal neurons. J. Physiol. 548, 245-258 (2003).
81. Forti, L., Bossi, M., Bergamaschi, A., Villa, A. & Malgaroli, A. Loose-patch recordings of single quanta at individual hippocampal synapses. Nature 388, 874-878 (1997). A direct measurement of the quantal response at putatively single synapses showing that quantal responses have small variability.
82. Silver, R. A., Cull-Candy, S. G. & Takahashi, T. Non-NMDA glutamate receptor occupancy and open probability at a rat cerebellar synapse with single and multiple release sites. J. Physiol. 494, 231-250 (1996).
83. Liu, G., Choi, S. & Tsien, R. W. Variability of neurotransmitter concentration and nonsaturation of postsynaptic AMPA receptors at synapses in hippocampal cultures and slices. Neuron 22, 395-409 (1999).
84. McAllister, A. K. & Stevens, C. F. Nonsaturation of AMPA and NMDA receptors at hippocampal synapses. Proc. Natl Acad. Sci. USA 97, 6173-6178 (2000).
85. Franks, K. M., Bartol, T. M. Jr. & Sejnowski, T. J. A Monte Carlo model reveals independent signaling at central glutamatergic synapses. Biophys. J. 83, 2333-2348 (2002).
86. Choi, S., Klingauf, J. & Tsien, R. W. Fusion pore modulation as a presynaptic mechanism contributing to expression of long-term potentiation. Philos. Trans. R. Soc. Lond. B Biol. Sci. 358, 695-705 (2003). A review of experiments pointing to the importance of the mode of vesicle release in AMPA channel activation. Experiments suggesting a role for this process in synaptic plasticity are also reviewed.
87. Liao, D., Hessler, N. A. & Malinow, R. Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice. Nature 375, 400-404 (1995).
88. Bekkers, J. M., Richerson, G. B. & Stevens, C. F. Origin of variability in quantal size in cultured hippocampal neurons and hippocampal slices. Proc. Natl Acad. Sci. USA 87, 5359-5362 (1990).
89. Hanse, E. & Gustafsson, B. Quantal variability at glutamatergic synapses in area CA1 of the rat neonatal hippocampus. J. Physiol. 531, 467-480 (2001).
90. Sahara, Y. & Takahashi, T. Quantal components of the excitatory postsynaptic currents at a rat central auditory synapse. J. Physiol. 536, 189-197 (2001).
91. Jonas, P., Major, G. & Sakmann, B. Quantal components of unitary EPSCs at the mossy fibre synapse on CA3 pyramidal cells of rat hippocampus. J. Physiol. 472, 615-663 (1993).
92. Franks, K. M., Stevens, C. F. & Sejnowski, T. J. Independent sources of quantal variability at single glutamatergic synapses. J. Neurosci. 23, 3186-3195 (2003).
93. Karunanithi, S., Marin, L., Wong, K. & Atwood, H. L. Quantal size and variation determined by vesicle size in normal and mutant Drosophila glutamatergic synapses. J. Neurosci. 22, 10267-10276 (2002).
94. Schikorski, T. & Stevens, C. F. Quantitative ultrastructural analysis of hippocampal excitatory synapses. J. Neurosci. 17, 5858-5867 (1997).
95. Wall, M. J. & Usowicz, M. M. Development of the quantal properties of evoked and spontaneous synaptic currents at a brain synapse. Nature Neurosci. 1, 675-682 (1998).
96. Ulrich, D. & Luscher, H. R. Miniature excitatory synaptic currents corrected for dendritic cable properties reveal quantal size and variance. J. Neurophysiol. 69, 1769-1773 (1993).
97. Yamashita, T., Ishikawa, T. & Takahashi, T. Developmental increase in vesicular glutamate content does not cause saturation of AMPA receptors at the calyx of held synapse. J. Neurosci. 23, 3633-3638 (2003).
98. Magee, J. C. & Cook, E. P. Somatic EPSP amplitude is independent of synapse location in hippocampal pyramidal neurons. Nature Neurosci. 3, 895-903 (2000). This paper combines local dendritic recording and focal sucrose application to measure the mEPSC with minimal dendritic filtering. This provides the most constrained measurement of the time-course of the mEPSC.
99. Bornstein, J. C. Spontaneous multiquantal release at synapses in guinea-pig hypogastric ganglia: evidence that release can occur in bursts. J. Physiol. 282, 375-398 (1978).
100. Paulsen, O. & Heggelund, P. The quantal size at retinogeniculate synapses determined from spontaneous and evoked EPSCs in guinea-pig thalamic slices. J. Physiol. 480, 505-511 (1994).
101. Paulsen, O. & Heggelund, P. Quantal properties of spontaneous EPSCs in neurones of the guinea-pig dorsal lateral geniculate nucleus. J. Physiol. 496, 759-772 (1996).
102. Min, M. Y. & Appenteng, K. Multimodal distribution of amplitudes of miniature and spontaneous EPSPs recorded in rat trigeminal motoneurones. J. Physiol. 494, 171-182 (1996).
103. Dennis, M. J., Harris, A. J. & Kuffler, S. W. Synaptic transmission and its duplication by focally applied acetylcholine in parasympathetic neurons in the heart of the frog. Proc. R. Soc. Lond. B Biol. Sci. 177, 509-539 (1971).
104. Liu, G. & Feldman, J. L. Quantal synaptic transmission in phrenic motor nucleus. J. Neurophysiol. 68, 1468-1471 (1992).
105. Edwards, F. A., Konnerth, A. & Sakmann, B. Quantal analysis of inhibitory synaptic transmission in the dentate gyrus of rat hippocampal slices: a patch-clamp study. J. Physiol. 430, 213-249 (1990).
106. Llano, I. et al. Presynaptic calcium stores underlie largeamplitude miniature IPSCs and spontaneous calcium transients. Nature Neurosci. 3, 1256-1265 (2000).
107. Melamed, N., Helm, P. J. & Rahamimoff, R. Confocal microscopy reveals coordinated calcium fluctuations and oscillations in synaptic boutons. J. Neurosci. 13, 632-649 (1993).
108. 2+ entry, and spontaneous transmitter release. Neuron 29, 197-208 (2001).
109. Simkus, C. R. & Stricker, C. The contribution of intracellular calcium stores to mEPSCs recorded in layer II neurones of rat barrel cortex. J. Physiol. 545, 521-535 (2002).
110. Galante, M. & Marty, A. Presynaptic ryanodinesensitive calcium stores contribute to evoked neurotransmitter release at the basket cell - Purkinje cell synapse. J. Neurosci. 23, 11229-11234 (2003).
111. Sharma, G. & Vijayaraghavan, S. Modulation of presynaptic store calcium induces release of glutamate and postsynaptic firing. Neuron 38, 929-939 (2003).
112. Jack, J. J., Larkman, A. U., Major, G. & Stratford, K. J. Quantal analysis of the synaptic excitation of CA1 hippocampal pyramidal cells. Adv. Second Messenger Phosphoprotein Res. 29, 275-299 (1994).
113. Nusser, Z. et al. Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron 21, 545-559 (1998).
114. Wilson, N. R. et al. Presynaptic regulation of quantal size by the vesicular glutamate transporter VGLUT1. J. Neurosci. 25, 6221-6234 (2005).
115. Wu, X. S. et al. The origin of quantal size variation: vesicular glutamate concentration plays a significant role. J. Neurosci. 27, 3046-3056 (2007).
116. Conti, R. & Lisman, J. The high variance of AMPA receptor- and NMDA receptor-mediated responses at single hippocampal synapses: evidence for multiquantal release. Proc. Natl Acad. Sci. USA 100, 4885-4890 (2003).
117. 2+ elevation occurs in unstimulated spines during the LTP pairing protocol but does not change synaptic strength. Hippocampus 12, 667-679 (2002).
118. Oertner, T. G., Sabatini, B. L., Nimchinsky, E. A. & Svoboda, K. Facilitation at single synapses probed with optical quantal analysis. Nature Neurosci. 5, 657-664 (2002). This paper uses two-photon calcium imaging to infer that multivesicular release can occur at single synapses.
119. Wadiche, J. I. & Jahr, C. E. Multivesicular release at climbing fiber-Purkinje cell synapses. Neuron 32, 301-313 (2001).
120. Foster, K. A., Kreitzer, A. C. & Regehr, W. G. Interaction of postsynaptic receptor saturation with presynaptic mechanisms produces a reliable synapse. Neuron 36, 1115-1126 (2002).
121. Christie, J. M. & Jahr, C. E. Multivesicular release at Schaffer collateral-CA1 hippocampal synapses. J. Neurosci. 26, 210-216 (2006).
122. Satzler, K. et al. Three-dimensional reconstruction of a calyx of Held and its postsynaptic principal neuron in the medial nucleus of the trapezoid body. J. Neurosci. 22, 10567-10579 (2002).
123. Biro, A. A., Holderith, N. B. & Nusser, Z. Quantal size is independent of the release probability at hippocampal excitatory synapses. J. Neurosci. 25, 223-232 (2005).
124. Stevens, C. F. & Wang, Y. Facilitation and depression at single central synapses. Neuron 14, 795-802 (1995).
125. Bolshakov, V. Y. & Siegelbaum, S. A. Regulation of hippocampal transmitter release during development and long-term potentiation. Science 269, 1730-1734 (1995).
126. Chen, G., Harata, N. C. & Tsien, R. W. Paired-pulse depression of unitary quantal amplitude at single hippocampal synapses. Proc. Natl Acad. Sci. USA 101, 1063-1068 (2004).
127. Silver, R. A., Lubke, J., Sakmann, B. & Feldmeyer, D. High-probability uniquantal transmission at excitatory synapses in barrel cortex. Science 302, 1981-1984 (2003).
128. Shapira, M. et al. Unitary assembly of presynaptic active zones from Piccolo-Bassoon transport vesicles. Neuron 38, 237-252 (2003).
129. Lisman, J. & Raghavachari, S. A unified model of the presynaptic and postsynaptic changes during LTP at CA1 synapses. Science's STKE [online] http://stke. sciencemag.org/cgi/content/full/sigtrans;2006/356/ re11 (2006).
130. Cathala, L., Holderith, N. B., Nusser, Z., DiGregorio, D. A. & Cull-Candy, S. G. Changes in synaptic structure underlie the developmental speeding of AMPA receptor-mediated EPSCs. Nature Neurosci. 8, 1310-1318 (2005).
131. Bolshakov, V. Y., Golan, H., Kandel, E. R. & Siegelbaum, S. A. Recruitment of new sites of synaptic transmission during the cAMP-dependent late phase of LTP at CA3-CA1 synapses in the hippocampus. Neuron 19, 635-651 (1997).
132. Ostroff, L. E., Fiala, J. C., Allwardt, B. & Harris, K. M. Polyribosomes redistribute from dendritic shafts into spines with enlarged synapses during LTP in developing rat hippocampal slices. Neuron 35, 535-545 (2002).
133. 2+ channels. Trends Pharmacol. Sci. 12, 349-354 (1991).
134. Catterall, W. A. Structure and function of voltagegated sodium and calcium channels. Curr. Opin. Neurobiol. 1, 5-13 (1991).
135. 2+ channels in mammalian central neurons. Trends Neurosci. 18, 89-98 (1995).
136. Nowycky, M. C., Fox, A. P. & Tsien, R. W. Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature 316, 440-443 (1985).
137. 2+ channels in evoked release of norepinephrine from sympathetic neurons. Science 239, 57-61 (1988).
138. Stanley, E. F. & Goping, G. Characterization of a calcium current in a vertebrate cholinergic presynaptic nerve terminal. J. Neurosci. 11, 985-993 (1991).
139. Stanley, E. F. Single calcium channels on a cholinergic presynaptic nerve terminal. Neuron 7, 585-591 (1991).
140. 2+ channels in the mammalian central nervous system. Trends Neurosci. 15, 351-355 (1992).
141. 1 subunits. Neuron 11, 291-303 (1993).
142. 2+ channel currents in rat cerebellar granule neurons. J. Neurosci. 15, 2995-3012 (1995).
143. Takahashi, T. & Momiyama, A. Different types of calcium channels mediate central synaptic transmission. Nature 366, 156-158 (1993).
144. Luebke, J. I., Dunlap, K. & Turner, T. J. Multiple calcium channel types control glutamatergic synaptic transmission in the hippocampus. Neuron 11, 895-902 (1993).
145. 2+ channels in supporting hippocampal synaptic transmission. Science 264, 107-111 (1994).
146. Forsythe, I. D. Direct patch recording from identified presynaptic terminals mediating glutamatergic EPSCs in the rat CNS in vitro. J. Physiol. 479, 381-387 (1994).
147. Ertel, E. A. et al. Nomenclature of voltage-gated calcium channels. Neuron 25, 533-535 (2000).
148. Olivera, B. M., Miljanich, G. P., Ramachandran, J. & Adams, M. E. Calcium channel diversity and neurotransmitter release: the ω-conotoxins and ω-agatoxins. Annu. Rev. Biochem. 63, 823-867 (1994).
149. Campbell, K. P., Leung, A. T. & Sharp, A. H. The biochemistry and molecular biology of the dihydropyridine-sensitive calcium channel. Trends Neurosci. 11, 425-430 (1988).
150. Scholz, K. P. & Miller, R. J. Developmental changes in presynaptic calcium channels coupled to glutamate release in cultured rat hippocampal neurons. J. Neurosci. 15, 4612-4617 (1995).
151. Tsien, R. W., Hess, P., McCleskey, E. W. & Rosenberg, R. L. Calcium channels: mechanisms of selectivity, permeation, and block. Annu. Rev. Biophys. Biophys. Chem. 16, 265-290 (1987).
152. Sather, W. A. & McCleskey, E. W. Permeation and selectivity in calcium channels. Annu. Rev. Physiol. 65, 133-159 (2003).
153. 2+ channelmutant mouse, tottering. J. Physiol. 547, 497-507 (2003).
154. Colecraft, H. M., Patil, P. G. & Yue, D. T. Differential occurrence of reluctant openings in G-protein-inhibited N- and P/Q-type calcium channels. J. Gen. Physiol. 115, 175-192 (2000).
155. Pietrobon, D. Calcium channels and channelopathies of the central nervous system. Mol. Neurobiol. 25, 31-50 (2002).
156. Miljanich, G. P. Ziconotide: neuronal calcium channel blocker for treating severe chronic pain. Curr. Med. Chem. 11, 3029-3040 (2004).
157. Choi, S., Klingauf, J. & Tsien, R. W. Postfusional regulation of cleft glutamate concentration during LTP at 'silent synapses'. Nature Neurosci. 3, 330-336 (2000).
158. Montgomery, J. M., Pavlidis, P. & Madison, D. V. Pair recordings reveal all-silent synaptic connections and the postsynaptic expression of long-term potentiation. Neuron 29, 691-701 (2001).
159. Renger, J. J., Egles, C. & Liu, G. A developmental switch in neurotransmitter flux enhances synaptic efficacy by affecting AMPA receptor activation. Neuron 29, 469-484 (2001).
160. Krupa, B. & Liu, G. Does the fusion pore contribute to synaptic plasticity? Trends Neurosci. 27, 62-66 (2004).
161. Photowala, H., Blackmer, T., Schwartz, E., Hamm, H. E. & Alford, S. G protein βγ-subunits activated by serotonin mediate presynaptic inhibition by regulating vesicle fusion properties. Proc. Natl Acad. Sci. USA 103, 4281-4286 (2006).
162. Zakharenko, S. S., Zablow, L. & Siegelbaum, S. A. Altered presynaptic vesicle release and cycling during mGluR-dependent LTD. Neuron 35, 1099-1110 (2002).
163. Nakagawa, T., Cheng, Y., Sheng, M. & Walz, T. Three-dimensional structure of an AMPA receptor without associated stargazin/TARP proteins. Biol. Chem. 387, 179-187 (2006).
164. Madden, D. R. The structure and function of glutamate receptor ion channels. Nature Rev. Neurosci. 3, 91-101 (2002).
165. Armstrong, N., Sun, Y., Chen, G. Q. & Gouaux, E. Structure of a glutamate-receptor ligand-binding core in complex with kainate. Nature 395, 913-917 (1998).
166. Armstrong, N. & Gouaux, E. Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core. Neuron 28, 165-181 (2000).
167. Sun, Y. et al. Mechanism of glutamate receptor desensitization. Nature 417, 245-253 (2002).
168. Armstrong, N., Jasti, J., Beich-Frandsen, M. & Gouaux, E. Measurement of conformational changes accompanying desensitization in an ionotropic glutamate receptor. Cell 127, 85-97 (2006). A structural study of AMPA channels that provides clear insight into the mechanism of desensitization.
169. Rosenmund, C., Stern-Bach, Y. & Stevens, C. F. The tetrameric structure of a glutamate receptor channel. Science 280, 1596-1599 (1998). An important paper demonstrating the tetrameric structure of AMPA channels and the fact that different channel occupancy by glutamate leads to different single-channel conductance.
170. Smith, T. C. & Howe, J. R. Concentration-dependent substate behavior of native AMPA receptors. Nature Neurosci. 3, 992-997 (2000).
171. Ruiz, M. & Karpen, J. W. Opening mechanism of a cyclic nucleotide-gated channel based on analysis of single channels locked in each liganded state. J. Gen. Physiol. 113, 873-895 (1999).
172. Ruiz, M. L. & Karpen, J. W. Single cyclic nucleotidegated channels locked in different ligand-bound states. Nature 389, 389-392 (1997).
173. Raman, I. M. & Trussell, L. O. The mechanism of α-amino-3- hydroxy-5-methyl-4-isoxazolepropionate receptor desensitization after removal of glutamate. Biophys. J. 68, 137-146 (1995).
174. Hausser, M. & Roth, A. Estimating the time course of the excitatory synaptic conductance in neocortical pyramidal cells using a novel voltage jump method. J. Neurosci. 17, 7606-7625 (1997).
175. Diamond, J. S. & Jahr, C. E. Transporters buffer synaptically released glutamate on a submillisecond time scale. J. Neurosci. 17, 4672-4687 (1997).
176. Postlethwaite, M., Hennig, M. H., Steinert, J. R., Graham, B. P. & Forsythe, I. D. Acceleration of AMPA receptor kinetics underlies temperature-dependent changes in synaptic strength at the rat calyx of Held. J. Physiol. 579, 69-84 (2007).
177. Robert, A. & Howe, J. R. How AMPA receptor desensitization depends on receptor occupancy. J. Neurosci. 23, 847-858 (2003).
178. Rostaing, P. et al. Analysis of synaptic ultrastructure without fixative using high-pressure freezing and tomography. Eur. J. Neurosci. 24, 3463-3474 (2006).
179. Siksou, L. et al. Three-dimensional architecture of presynaptic terminal cytomatrix. J. Neurosci. 27, 6868-6877 (2007).