Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Feature Review
  • Published:

Active zones for presynaptic plasticity in the brain

Molecular Psychiatry volume 10, pages 185–200 (2005)Cite this article

Abstract

Some of the most abundant synapses in the brain such as the synapses formed by the hippocampal mossy fibers, cerebellar parallel fibers and several types of cortical afferents express presynaptic forms of long-term potentiation (LTP), a putative cellular model for spatial, motor and fear learning. Those synapses often display presynaptic mechanisms of LTP induction, which are either NMDA receptor independent of dependent of presynaptic NMDA receptors. Recent investigations on the molecular mechanisms of neurotransmitter release modulation in short- and long-term synaptic plasticity in central synapses give a preponderant role to active zone proteins as Munc-13 and RIM1-alpha, and point toward the maturation process of synaptic vesicles prior to Ca2+-dependent fusion as a key regulatory step of presynaptic plasticity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Regehr WG, Stevens CF . Physiology of synaptic transmission and short term synaptic plasticity. In: Cowan WM, Südhof TC, Stevens CF (eds). The Synapse. Johns Hopkins University Press: Baltimore, 2000.

    Google Scholar 

  2. Zucker RS, Regehr WG . Short-term synaptic plasticity. Annu Rev Physiol 2002; 64: 355–405.

    Article  CAS  PubMed  Google Scholar 

  3. 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 1973; 232: 331–356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Humeau Y, Shaban H, Bissiere S, Luthi A . Presynaptic induction of heterosynaptic associative plasticity in the mammalian brain. Nature 2003; 426: 841–845.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  6. Nicoll RA, Malenka RC . Contrasting properties of two forms of long-term potentiation in the hippocampus. Nature 1995; 377: 115–118.

    Article  CAS  PubMed  Google Scholar 

  7. Kandel ER . The molecular biology of memory storage: a dialogue between genes and synapses. Science 2001; 294: 1030–1038.

    Article  CAS  PubMed  Google Scholar 

  8. Malenka RC, Siegelbaum SA . Synaptic plasticity. In: Cowan WM, Südhof TC, Stevens CF (eds). The Synapse. Johns Hopkins University Press: Baltimore, 2000, pp 455–518.

    Google Scholar 

  9. Malenka RC . The long-term potential of LTP. Nat Rev Neurosci 2003; 4: 923–926.

    Article  CAS  PubMed  Google Scholar 

  10. Grimwood PD, Martin SJ, Morris RGM . Synaptic plasticity and memory. In: Cowan WM, Südhof TC, Stevens CF (eds). The Synapse. Johns Hopkins University Press: Baltimore, 2000, pp 519–570.

    Google Scholar 

  11. Malinow R, Malenka RC . AMPA receptor trafficking and synaptic plasticity. Annu Rev Neurosci 2002; 25: 103–126.

    Article  CAS  PubMed  Google Scholar 

  12. Bredt DS, Nicoll RA . AMPA receptor trafficking at excitatory synapses. Neuron 2003; 40: 361–379.

    Article  CAS  PubMed  Google Scholar 

  13. Stevens CF, Wang Y . Changes in reliability of synaptic function as a mechanism for plasticity. Nature 1994; 371: 704–707.

    Article  CAS  PubMed  Google Scholar 

  14. Bolshakov VY, Siegelbaum SA . Hippocampal long-term depression: arachidonic acid as a potential retrograde messenger. Neuropharmacology 1995; 34: 1581–1587.

    Article  CAS  PubMed  Google Scholar 

  15. Malgaroli A, Ting AE, Wendland B, Bergamaschi A, Villa A, Tsien RW et al. Presynaptic component of long-term potentiation visualized at individual hippocampal synapses. Science 1995; 268: 1624–1628.

    Article  CAS  PubMed  Google Scholar 

  16. Ryan TA, Ziv NE, Smith SJ . Potentiation of evoked vesicle turnover at individually resolved synaptic boutons. Neuron 1996; 17: 125–134.

    Article  CAS  PubMed  Google Scholar 

  17. Zakharenko SS, Zablow L, Siegelbaum SA . Visualization of changes in presynaptic function during long-term synaptic plasticity. Nat Neurosci 2001; 4: 711–717.

    Article  CAS  PubMed  Google Scholar 

  18. Emptage NJ, Reid CA, Fine A, Bliss TV . Optical quantal analysis reveals a presynaptic component of LTP at hippocampal Schaffer-associational synapses. Neuron 2003; 38: 797–804.

    Article  CAS  PubMed  Google Scholar 

  19. Harris EW, Cotman CW . Long-term potentiation of guinea pig mossy fiber responses is not blocked by N-methyl D-aspartate antagonists. Neurosci Lett 1986; 70: 132–137.

    Article  CAS  PubMed  Google Scholar 

  20. Zalutsky RA, Nicoll RA . Comparison of two forms of long-term potentiation in single hippocampal neurons. Science 1990; 248: 1619–1624.

    Article  CAS  PubMed  Google Scholar 

  21. Ito I, Sugiyama H . Roles of glutamate receptors in long-term potentiation at hippocampal mossy fiber synapses. Neuroreport 1991; 2: 333–336.

    Article  CAS  PubMed  Google Scholar 

  22. Katsuki H, Kaneko S, Tajima A, Satoh M . Separate mechanisms of long-term potentiation in two input systems to CA3 pyramidal neurons of rat hippocampal slices as revealed by the whole-cell patch-clamp technique. Neurosci Res 1991; 12: 393–402.

    Article  CAS  PubMed  Google Scholar 

  23. Castillo PE, Weisskopf MG, Nicoll RA . The role of Ca2+ channels in hippocampal mossy fiber synaptic transmission and long-term potentiation. Neuron 1994; 12: 261–269.

    Article  CAS  PubMed  Google Scholar 

  24. Maeda T, Kaneko S, Akaike A, Satoh M . Direct evidence for increase in excitatory amino acids release during mossy fiber LTP in rat hippocampal slices as revealed by the patch sensor methods. Neurosci Lett 1997; 224: 103–106.

    Article  CAS  PubMed  Google Scholar 

  25. Langdon RB, Johnson JW, Barrionuevo G . Posttetanic potentiation and presynaptically induced long-term potentiation at the mossy fiber synapse in rat hippocampus. J Neurobiol 1995; 26: 370–385.

    Article  CAS  PubMed  Google Scholar 

  26. Mellor J, Nicoll RA . Hippocampal mossy fiber LTP is independent of postsynaptic calcium. Nat Neurosci 2001; 4: 125–126.

    Article  CAS  PubMed  Google Scholar 

  27. Williams S, Johnston D . Long-term potentiation of hippocampal mossy fiber synapses is blocked by postsynaptic injection of calcium chelators. Neuron 1989; 3: 583–588.

    Article  CAS  PubMed  Google Scholar 

  28. Yamamoto C, Sawada S, Kamiya H . Enhancement of postsynaptic responsiveness during long-term potentiation of mossy fiber synapses in guinea pig hippocampus. Neurosci Lett 1992; 138: 111–114.

    Article  CAS  PubMed  Google Scholar 

  29. Yeckel MF, Kapur A, Johnston D . Multiple forms of LTP in hippocampal CA3 neurons use a common postsynaptic mechanism. Nat Neurosci 1999; 2: 625–633.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang J, Yeckel MF, Johnston D, Zucker RS . Photolysis of postsynaptic caged Ca2+ can potentiate and depress mossy fiber synaptic responses in rat hippocampal CA3 pyramidal neurons. J Neurophysiol 2004; 91: 1596–1607.

    Article  PubMed  Google Scholar 

  31. Staubli U, Larson J, Lynch G . Mossy fiber potentiation and long-term potentiation involve different expression mechanisms. Synapse 1990; 5: 333–335.

    Article  CAS  PubMed  Google Scholar 

  32. Huang YY, Li XC, Kandel ER . cAMP contributes to mossy fiber LTP by initiating both a covalently mediated early phase and macromolecular synthesis-dependent late phase. Cell 1994; 79: 69–79.

    Article  CAS  PubMed  Google Scholar 

  33. Xiang Z, Greenwood AC, Kairiss EW, Brown TH . Quantal mechanism of long-term potentiation in hippocampal mossy-fiber synapses. J Neurophysiol 1994; 71: 2552–2556.

    Article  CAS  PubMed  Google Scholar 

  34. Rosenmund C, Clements JD, Westbrook GL . Nonuniform probability of glutamate release at a hippocampal synapse. Science 1993; 262: 754–757.

    Article  CAS  PubMed  Google Scholar 

  35. Hessler NA, Shirke AM, Malinow R . The probability of transmitter release at a mammalian central synapse. Nature 1993; 366: 569–572.

    Article  CAS  PubMed  Google Scholar 

  36. Weisskopf MG, Nicoll RA . Presynaptic changes during mossy fibre LTP revealed by NMDA receptor-mediated synaptic responses. Nature 1995; 376: 256–259.

    Article  CAS  PubMed  Google Scholar 

  37. Weisskopf MG, Castillo PE, Zalutsky RA, Nicoll RA . Mediation of hippocampal mossy fiber long-term potentiation by cyclic AMP. Science 1994; 265: 1878–1882.

    Article  CAS  PubMed  Google Scholar 

  38. Tong G, Malenka RC, Nicoll RA . Long-term potentiation in cultures of single hippocampal granule cells: a presynaptic form of plasticity. Neuron 1996; 16: 1147–1157.

    Article  CAS  PubMed  Google Scholar 

  39. Lopez-Garcia JC, Arancio O, Kandel ER, Baranes D . A presynaptic locus for long-term potentiation of elementary synaptic transmission at mossy fiber synapses in culture. Proc Natl Acad Sci USA 1996; 93: 4712–4717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kullmann DM . Silent synapses: what are they telling us about long-term potentiation? Philos Trans Roy Soc London B Biol Sci 2003; 358: 727–733.

    Article  CAS  Google Scholar 

  41. Voronin LL, Cherubini E . ‘Deaf, mute and whispering’ silent synapses: their role in synaptic plasticity. J Physiol 2004; 557(Part 1): 3–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hallermann S et al. A large pool of releasable vesicles in a cortical glutamatergic synapse. Proc Natl Acad Sci USA 2003; 100: 8975–8980.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ramon y Cajal S . Histologie du Systeme Nerveux de l'Homme et des Vertebres. Maloine: Paris, 1911.

  44. Henze DA, Urban NN, Barrionuevo G . The multifarious hippocampal mossy fiber pathway: a review. Neuroscience 2000; 98: 407–427.

    Article  CAS  PubMed  Google Scholar 

  45. 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 1993; 472: 615–663.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Reid CA, Dixon DB, Takahashi M, Bliss TV, Fine A . Optical quantal analysis indicates that long-term potentiation at single hippocampal mossy fiber synapses is expressed through increased release probability. recruitment of new release sites. and activation of silent synapses. J Neurosci 2004; 24: 3618–3626.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Reid CA, Fabian-Fine R, Fine A . Postsynaptic calcium transients evoked by activation of individual hippocampal mossy fiber synapses. J Neurosci 2001; 21: 2206–2214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Alvarez de Toledo G, Fernandez-Chacon R, Fernandez JM . Release of secretory products during transient vesicle fusion. Nature 1993; 363: 554–558.

    Article  CAS  PubMed  Google Scholar 

  49. Ales E, Tabares L, Poyato JM, Valero V, Lindau M, Alvarez de Toledo G . High calcium concentrations shift the mode of exocytosis to the kiss-and-run mechanism. Nat Cell Biol 1999; 1: 40–44.

    Article  CAS  PubMed  Google Scholar 

  50. Gandhi SP, Stevens CF . Three modes of synaptic vesicular recycling revealed by single-vesicle imaging. Nature 2003; 423: 607–613.

    Article  CAS  PubMed  Google Scholar 

  51. Aravanis AM, Pyle JL, Tsien RW . Single synaptic vesicles fusing transiently and successively without loss of identity. Nature 2003; 423: 643–647.

    Article  CAS  PubMed  Google Scholar 

  52. Fernandez-Chacon R, Alvarez de Toledo G . Cytosolic calcium facilitates release of secretory products after exocytotic vesicle fusion. FEBS Lett 1995; 363: 221–225.

    Article  CAS  PubMed  Google Scholar 

  53. Hartmann J, Lindau M . A novel Ca(2+)-dependent step in exocytosis subsequent to vesicle fusion. FEBS Lett 1995; 363: 217–220.

    Article  CAS  PubMed  Google Scholar 

  54. Scepek S, Coorssen JR, Lindau M . Fusion pore expansion in horse eosinophils is modulated by Ca2+ and protein kinase C via distinct mechanisms. EMBO J 1998; 17: 4340–4345.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Choi S, Klingauf J, Tsien RW . Postfusional regulation of cleft glutamate concentration during LTP at ‘silent synapses’. Nat Neurosci 2000; 3: 330–336.

    Article  CAS  PubMed  Google Scholar 

  56. Renger JJ, Egles C, Liu G . A developmental switch in neurotransmitter flux enhances synaptic efficacy by affecting AMPA receptor activation. Neuron 2001; 29: 469–484.

    Article  CAS  PubMed  Google Scholar 

  57. Nielsen TA, DiGregorio DA, Silver RA . Modulation of glutamate mobility reveals the mechanism underlying slow-rising ampar epscs and the diffusion coefficient in the synaptic cleft. Neuron 2004; 42: 757–771.

    Article  CAS  PubMed  Google Scholar 

  58. Malenka RC, Nicoll RA . Long-term potentiation–a decade of progress? Science 1999; 285: 1870–1874.

    Article  CAS  PubMed  Google Scholar 

  59. Nicoll RA . Expression mechanisms underlying long-term potentiation: a postsynaptic view. Philos Trans Roy Soc London B Biol Sci 2003; 358: 721–726.

    Article  CAS  Google Scholar 

  60. Griffith LC . Regulation of calcium/calmodulin-dependent protein kinase II activation by intramolecular and intermolecular interactions. J Neurosci 2004; 24: 8394–8398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Elgersma Y, Sweatt JD, Giese KP . Mouse genetic approaches to investigating calcium/calmodulin-dependent protein kinase II function in plasticity and cognition. J Neurosci 2004; 24: 8410–8415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Hinds HL, Goussakov I, Nakazawa K, Tonegawa S, Bolshakov VY . Essential function of alpha-calcium/calmodulin-dependent protein kinase II in neurotransmitter release at a glutamatergic central synapse. Proc Natl Acad Sci USA 2003; 100: 4275–4280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ninan I, Arancio O . Presynaptic CaMKII is necessary for synaptic plasticity in cultured hippocampal neurons. Neuron 2004; 42: 129–141.

    Article  CAS  PubMed  Google Scholar 

  64. Wang H, Storm DR . Calmodulin-regulated adenylyl cyclases: cross-talk and plasticity in the central nervous system. Mol Pharmacol 2003; 63: 463–468.

    Article  PubMed  Google Scholar 

  65. Huang YY, Kandel ER . Modulation of both the early and the late phase of mossy fiber LTP by the activation of beta-adrenergic receptors. Neuron 1996; 16: 611–617.

    Article  CAS  PubMed  Google Scholar 

  66. Kamiya H, Umeda K, Ozawa S, Manabe T . Presynaptic Ca2+ entry is unchanged during hippocampal mossy fiber long-term potentiation. J Neurosci 2002; 22: 10524–10528.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bortolotto ZA, Clarke VR, Delany CM, Parry MC, Smolders I, Vignes M et al. Kainate receptors are involved in synaptic plasticity. Nature 1999; 402: 297–301.

    Article  CAS  PubMed  Google Scholar 

  68. Schmitz D, Mellor J, Breustedt J, Nicoll RA . Presynaptic kainate receptors impart an associative property to hippocampal mossy fiber long-term potentiation. Nat Neurosci 2003; 6: 1058–1063.

    Article  CAS  PubMed  Google Scholar 

  69. Rodriguez-Moreno A, Sihra TS . Presynaptic kainate receptor facilitation of glutamate release involves protein kinase A in the rat hippocampus. J Physiol 2004; 557(Part 3): 733–745.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Schmitz D, Mellor J, Frerking M, Nicoll RA . Presynaptic kainate receptors at hippocampal mossy fiber synapses. Proc Natl Acad Sci USA 2001; 98: 11003–11008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Lerma J . Roles and rules of kainate receptors in synaptic transmission. Nat Rev Neurosci 2003; 4: 481–495.

    Article  CAS  PubMed  Google Scholar 

  72. Bortolotto ZA, Lauri S, Isaac JT, Collingridge GL . Kainate receptors and the induction of mossy fibre long-term potentiation. Philos Trans Roy Soc London B 2003; 358: 657–666.

    Article  CAS  Google Scholar 

  73. Engelman HS, MacDermott AB . Presynaptic ionotropic receptors and control of transmitter release. Nat Rev Neurosci 2004; 5: 135–145.

    Article  CAS  PubMed  Google Scholar 

  74. Hansel C, Linden DJ, D'Angelo E . Beyond parallel fiber LTD: the diversity of synaptic and non-synaptic plasticity in the cerebellum. Nat Neurosci 2001; 4: 467–475.

    Article  CAS  PubMed  Google Scholar 

  75. Bear MF, Linden DJ . The mechanisms and meaning of long-term synaptic depression. In: Cowan WM, Südhof TC, Stevens CF (eds). The Synapse. Johns Hopkins University Press: Baltimore, 2000, pp 455–517.

    Google Scholar 

  76. Linden DJ . Neuroscience. From molecules to memory in the cerebellum. Science 2003; 301: 1682–1685.

    Article  CAS  PubMed  Google Scholar 

  77. Koekkoek SK, Hulscher HC, Dortland BR, Hensbroek RA, Elgersma Y, Ruigrok TJ et al. Cerebellar LTD and learning-dependent timing of conditioned eyelid responses. Science 2003; 301: 1736–1739.

    Article  CAS  PubMed  Google Scholar 

  78. Medina JF, Nores WL, Ohyama T, Mauk MD . Mechanisms of cerebellar learning suggested by eyelid conditioning. Curr Opin Neurobiol 2000; 10: 717–724.

    Article  CAS  PubMed  Google Scholar 

  79. Sakurai M . Calcium is an intracellular mediator of the climbing fiber in induction of cerebellar long-term depression. Proc Natl Acad Sci USA 1990; 87: 3383–3385.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Sakurai M . Synaptic modification of parallel fibre-Purkinje cell transmission in in vitro guinea-pig cerebellar slices. J Physiol (London) 1987; 394: 463–480.

    Article  CAS  Google Scholar 

  81. Salin PA, Malenka RC, Nicoll RA . Cyclic AMP mediates a presynaptic form of LTP at cerebellar parallel fiber synapses. Neuron 1996; 16: 797–803.

    Article  CAS  PubMed  Google Scholar 

  82. Hirano T . Depression and potentiation of the synaptic transmission between a granule cell and a Purkinje cell in rat cerebellar culture. Neurosci Lett 1990; 119: 141–144.

    Article  CAS  PubMed  Google Scholar 

  83. Hirano T . Differential pre- and postsynaptic mechanisms for synaptic potentiation and depression between a granule cell and a Purkinje cell in rat cerebellar culture. Synapse 1991; 7: 321–323.

    Article  CAS  PubMed  Google Scholar 

  84. Crepel F, Jaillard D . Pairing of pre- and postsynaptic activities in cerebellar Purkinje cells induces long-term changes in synaptic efficacy in vitro. J Physiol 1991; 432: 123–141.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Shibuki K, Okada D . Cerebellar long-term potentiation under suppressed postsynaptic Ca2+ activity. Neuroreport 1992; 3: 231–234.

    Article  CAS  PubMed  Google Scholar 

  86. Linden DJ . Long-term potentiation of glial synaptic currents in cerebellar culture. Neuron 1997; 18: 983–994.

    Article  CAS  PubMed  Google Scholar 

  87. Linden DJ . Synaptically-evoked glutamate transport currents may be used to detect the expression of long-term potentiation in cerebellar culture. J Neurophysiol 1998; 79: 3151–3156.

    Article  CAS  PubMed  Google Scholar 

  88. Linden DJ, Ahn S . Activation of presynaptic cAMP-dependent protein kinase is required for induction of cerebellar long-term potentiation. J Neurosci 1999; 19: 10221–10227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Chavis P, Mollard P, Bockaert J, Manzoni O . Visualization of cyclic AMP-regulated presynaptic activity at cerebellar granule cells. Neuron 1998; 20: 773–781.

    Article  CAS  PubMed  Google Scholar 

  90. Sherman SM, Guillery RW . The Synaptic Organization of the Brain. In: Shepherd GM (ed). Thalamus. Oxford University Press: Oxford, 2004, pp 311–360.

    Google Scholar 

  91. Guillery RW, Sherman SM . Thalamic relay functions and their role in corticocortical communication: generalizations from the visual system. Neuron 2002; 33: 163–175.

    Article  CAS  PubMed  Google Scholar 

  92. Frigyesi TL . Intracellular recordings from neurons in dorsolateral thalamic reticular nucleus during capsular. basal ganglia and midline thalamic stimulation. Brain Res 1972; 48: 157–172.

    Article  CAS  PubMed  Google Scholar 

  93. Scharfman HE, Lu SM, Guido W, Adams PR, Sherman SM . N-methyl-D-aspartate receptors contribute to excitatory postsynaptic potentials of cat lateral geniculate neurons recorded in thalamic slices. Proc Natl Acad Sci USA 1990; 87: 4548–4552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Steriade M, Timofeev I . Short-term plasticity during intrathalamic augmenting responses in decorticated cats. J Neurosci 1997; 17: 3778–3795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. von Krosigk M, Monckton JE, Reiner PB, McCormick DA . Dynamic properties of corticothalamic excitatory postsynaptic potentials and thalamic reticular inhibitory postsynaptic potentials in thalamocortical neurons of the guinea-pig dorsal lateral geniculate nucleus. Neuroscience 1999; 91: 7–20.

    Article  CAS  PubMed  Google Scholar 

  96. Castro-Alamancos MA, Calcagnotto ME . Presynaptic long-term potentiation in corticothalamic synapses. J Neurosci 1999; 19: 9090–9097.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Deschenes M, Hu B . Membrane resistance increase induced in thalamic neurons by stimulation of brainstem cholinergic afferents. Brain Res 1990; 513: 339–342.

    Article  CAS  PubMed  Google Scholar 

  98. Lindstrom S, Wrobel A . Frequency dependent corticofugal excitation of principal cells in the cat's dorsal lateral geniculate nucleus. Exp Brain Res 1990; 79: 313–318.

    Article  CAS  PubMed  Google Scholar 

  99. Tsumoto T, Creutzfeldt OD, Legendy CR . Functional organization of the corticofugal system from visual cortex to lateral geniculate nucleus in the cat (with an appendix on geniculo-cortical mono-synaptic connections). Exp Brain Res 1978; 32: 345–364.

    Article  CAS  PubMed  Google Scholar 

  100. Casado M, Dieudonne S, Ascher P . Presynaptic N-methyl-D-aspartate receptors at the parallel fiber-Purkinje cell synapse. Proc Natl Acad Sci USA 2000; 97: 11593–11597.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Casado M, Isope P, Ascher P . Involvement of presynaptic N-methyl-D-aspartate receptors in cerebellar long-term depression. Neuron 2002; 33: 123–130.

    Article  CAS  PubMed  Google Scholar 

  102. Duguid IC, Smart TG . Retrograde activation of presynaptic NMDA receptors enhances GABA release at cerebellar interneuron-Purkinje cell synapses. Nat Neurosci 2004; 7: 525–533.

    Article  CAS  PubMed  Google Scholar 

  103. LeDoux JE . Emotion circuits in the brain. Annu Rev Neurosci 2000; 23: 155–184.

    Article  CAS  PubMed  Google Scholar 

  104. Stevens CF . A million dollar question: does LTP=memory? Neuron 1998; 20: 1–2.

    Article  CAS  PubMed  Google Scholar 

  105. Huang YY, Kandel ER . Postsynaptic induction and PKA-dependent expression of LTP in the lateral amygdala. Neuron 1998; 21: 169–178.

    Article  CAS  PubMed  Google Scholar 

  106. Bauer EP, Schafe GE, LeDoux JE . NMDA receptors and L-type voltage-gated calcium channels contribute to long-term potentiation and different components of fear memory formation in the lateral amygdala. J Neurosci 2002; 22: 5239–5249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. McKernan MG, Shinnick-Gallagher P . Fear conditioning induces a lasting potentiation of synaptic currents in vitro. Nature 1997; 390: 607–611.

    Article  CAS  PubMed  Google Scholar 

  108. Tsvetkov E, Carlezon WA, Benes FM, Kandel ER, Bolshakov VY . Fear conditioning occludes LTP-induced presynaptic enhancement of synaptic transmission in the cortical pathway to the lateral amygdala. Neuron 2002; 34: 289–300.

    Article  CAS  PubMed  Google Scholar 

  109. Bailey CH, Giustetto M, Huang YY, Hawkins RD, Kandel ER . Is heterosynaptic modulation essential for stabilizing Hebbian plasticity and memory? Nat Rev Neurosci 2000; 1: 11–20.

    Article  CAS  PubMed  Google Scholar 

  110. Pare D . Presynaptic induction and expression of NMDA-dependent LTP. Trends Neurosci 2004; 27: 440–441.

    Article  CAS  PubMed  Google Scholar 

  111. Farb CR, Ledoux JE . Afferents from rat temporal cortex synapse on lateral amygdala neurons that express NMDA and AMPA receptors. Synapse 1999; 33: 218–229.

    Article  CAS  PubMed  Google Scholar 

  112. Ohno-Shosaku T, Maejima T, Kano M . Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals. Neuron 2001; 29: 729–738.

    Article  CAS  PubMed  Google Scholar 

  113. Kreitzer AC, Regehr WG . Cerebellar depolarization-induced suppression of inhibition is mediated by endogenous cannabinoids. J Neurosci 2001; 21: RC174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Kreitzer AC, Regehr WG . Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. Neuron 2001; 29: 717–727.

    Article  CAS  PubMed  Google Scholar 

  115. Takahashi KA, Linden DJ . Cannabinoid receptor modulation of synapses received by cerebellar Purkinje cells. J Neurophysiol 2000; 83: 1167–1180.

    Article  CAS  PubMed  Google Scholar 

  116. Wilson RI, Kunos G, Nicoll RA . Presynaptic specificity of endocannabinoid signaling in the hippocampus. Neuron 2001; 31: 453–462.

    Article  CAS  PubMed  Google Scholar 

  117. Tzingounis AV, Nicoll RA . Presynaptic NMDA receptors get into the act. Nat Neurosci 2004; 7: 419–420.

    Article  CAS  PubMed  Google Scholar 

  118. Silver RA, Momiyama A, Cull-Candy SG . Locus of frequency-dependent depression identified with multiple-probability fluctuation analysis at rat climbing fibre-Purkinje cell synapses. J Physiol 1998; 510(Part 3): 881–902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Llano I, Gonzalez J, Caputo C, Lai FA, Blayney LM, Tan YP et al. Presynaptic calcium stores underlie large-amplitude miniature IPSCs and spontaneous calcium transients. Nat Neurosci 2000; 3: 1256–1265.

    Article  CAS  PubMed  Google Scholar 

  120. Galante M, Marty A . Presynaptic ryanodine-sensitive calcium stores contribute to evoked neurotransmitter release at the basket cell-Purkinje cell synapse. J Neurosci 2003; 23: 11229–11234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Sudhof TC . The synaptic vesicle cycle: a cascade of protein-protein interactions. Nature 1995; 375: 645–653.

    Article  CAS  PubMed  Google Scholar 

  122. Sudhof TC . The synaptic vesicle cycle. Annu Rev Neurosci 2004; 27: 509–547.

    Article  CAS  PubMed  Google Scholar 

  123. Rosenmund C, Rettig J, Brose N . Molecular mechanisms of active zone function. Curr Opin Neurobiol 2003; 13: 509–519.

    Article  CAS  PubMed  Google Scholar 

  124. Varoqueaux F, Sigler A, Rhee JS, Brose N, Enk C, Reim K et al. Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming. Proc Natl Acad Sci USA 2002; 99: 9037–9042.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Rosenmund C, Sigler A, Augustin I, Reim K, Brose N, Rhee JS . Differential control of vesicle priming and short-term plasticity by Munc13 isoforms. Neuron 2002; 33: 411–424.

    Article  CAS  PubMed  Google Scholar 

  126. Calakos N, Schoch S, Sudhof TC, Malenka RC . Multiple roles for the active zone protein RIM1alpha in late stages of neurotransmitter release. Neuron 2004; 42: 889–896.

    Article  CAS  PubMed  Google Scholar 

  127. Brose N, Hofmann K, Hata Y, Sudhof TC . Mammalian homologues of Caenorhabditis elegans unc-13 gene define novel family of C2-domain proteins. J Biol Chem 1995; 270: 25273–25280.

    Article  CAS  PubMed  Google Scholar 

  128. Richmond JE, Davis WS, Jorgensen EM . UNC-13 is required for synaptic vesicle fusion in C. elegans. Nat Neurosci 1999; 2: 959–964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Aravamudan B, Fergestad T, Davis WS, Rodesch CK, Broadie K . Drosophila UNC-13 is essential for synaptic transmission. Nat Neurosci 1999; 2: 965–971.

    Article  CAS  PubMed  Google Scholar 

  130. Augustin I, Rosenmund C, Sudhof TC, Brose N . Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles. Nature 1999; 400: 457–461.

    Article  CAS  PubMed  Google Scholar 

  131. Brose N, Rosenmund C, Rettig J . Regulation of transmitter release by Unc-13 and its homologues. Curr Opin Neurobiol 2000; 10: 303–311.

    Article  CAS  PubMed  Google Scholar 

  132. Betz A, Okamoto M, Benseler F, Brose N . Direct interaction of the rat unc-13 homologue Munc13-1 with the N terminus of syntaxin. J Biol Chem 1997; 272: 2520–2526.

    Article  CAS  PubMed  Google Scholar 

  133. Richmond JE, Weimer RM, Jorgensen EM . An open form of syntaxin bypasses the requirement for UNC-13 in vesicle priming. Nature 2001; 412: 338–341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Betz A, Ashery U, Rickmann M, Augustin I, Neher E, Sudhof TC et al. Munc13-1 is a presynaptic phorbol ester receptor that enhances neurotransmitter release. Neuron 1998; 21: 123–136.

    Article  CAS  PubMed  Google Scholar 

  135. Junge HJ, Rhee JS, Jahn O, Varoqueaux F, Spiess J, Waxham MN et al. Calmodulin and Munc13 form a Ca2+ sensor/effector complex that controls short-term synaptic plasticity. Cell 2004; 118: 389–401.

    Article  CAS  PubMed  Google Scholar 

  136. Ashery U, Varoqueaux F, Voets T, Betz A, Thakur P, Koch H et al. Munc13-1 acts as a priming factor for large dense-core vesicles in bovine chromaffin cells. EMBO J 2000; 19: 3586–3596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Rhee JS, Betz A, Pyott S, Reim K, Varoqueaux F, Augustin I et al. Beta phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs. Cell 2002; 108: 121–133.

    Article  CAS  PubMed  Google Scholar 

  138. Rosenmund C, Stevens CF . Definition of the readily releasable pool of vesicles at hippocampal synapses. Neuron 1996; 16: 1197–1207.

    Article  CAS  PubMed  Google Scholar 

  139. Brose N, Rosenmund C . Move over protein kinase C, you've got company: alternative cellular effectors of diacylglycerol and phorbol esters. J Cell Sci 2002; 115(Part 23): 4399–4411.

    Article  CAS  PubMed  Google Scholar 

  140. Dittman JS, Regehr WG . Calcium dependence and recovery kinetics of presynaptic depression at the climbing fiber to Purkinje cell synapse. J Neurosci 1998; 18: 6147–6162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Stevens CF, Wesseling JF . Activity-dependent modulation of the rate at which synaptic vesicles become available to undergo exocytosis. Neuron 1998; 21: 415–424.

    Article  CAS  PubMed  Google Scholar 

  142. Wang LY, Kaczmarek LK . High-frequency firing helps replenish the readily releasable pool of synaptic vesicles. Nature 1998; 394: 384–388.

    Article  CAS  PubMed  Google Scholar 

  143. Sakaba T, Neher E . Calmodulin mediates rapid recruitment of fast-releasing synaptic vesicles at a calyx-type synapse. Neuron 2001; 32: 1119–1131.

    Article  CAS  PubMed  Google Scholar 

  144. Augustin I, Korte S, Rickmann M, Kretzschmar HA, Sudhof TC, Herms JW et al. The cerebellum-specific Munc13 isoform Munc13-3 regulates cerebellar synaptic transmission and motor learning in mice. J Neurosci 2001; 21: 10–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Wang Y, Okamoto M, Schmitz F, Hofmann K, Sudhof TC . Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion. Nature 1997; 388: 593–598.

    Article  CAS  PubMed  Google Scholar 

  146. Wang Y, Sudhof TC . Genomic definition of RIM proteins: evolutionary amplification of a family of synaptic regulatory proteins(small star, filled). Genomics 2003; 81: 126–137.

    Article  CAS  PubMed  Google Scholar 

  147. Betz A, Thakur P, Junge HJ, Ashery U, Rhee JS, Scheuss V et al. Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming. Neuron 2001; 30: 183–196.

    Article  CAS  PubMed  Google Scholar 

  148. Wang Y, Dulubova I, Rizo J, Sudhof TC . Functional analysis of conserved structural elements in yeast syntaxin Vam3p. J Biol Chem 2001; 276: 28598–28605.

    Article  CAS  PubMed  Google Scholar 

  149. Ohtsuka T, Takao-Rikitsu E, Inoue E, Inoue M, Takeuchi M, Matsubara K et al. Cast: a novel protein of the cytomatrix at the active zone of synapses that forms a ternary complex with RIM1 and munc13-1. J Cell Biol 2002; 158: 577–590.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Wang Y, Liu X, Biederer T, Sudhof TC . A family of RIM-binding proteins regulated by alternative splicing: Implications for the genesis of synaptic active zones. Proc Natl Acad Sci USA 2002; 99: 14464–14469.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Coppola T, Magnin-Luthi S, Perret-Menoud V, Gattesco S, Schiavo G, Regazzi R . Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-25, and synaptotagmin. J Biol Chem 2001; 276: 32756–32762.

    Article  CAS  PubMed  Google Scholar 

  152. Schoch S, Castillo PE, Jo T, Mukherjee K, Geppert M, Wang Y et al. RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone. Nature 2002; 415: 321–326.

    Article  CAS  PubMed  Google Scholar 

  153. Hibino H, Pironkova R, Onwumere O, Vologodskaia M, Hudspeth AJ, Lesage F . RIM binding proteins (RBPs) couple Rab3-interacting molecules (RIMs) to voltage-gated Ca(2+) channels. Neuron 2002; 34: 411–423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Koushika SP, Richmond JE, Hadwiger G, Weimer RM, Jorgensen EM, Nonet ML . A post-docking role for active zone protein Rim. Nat Neurosci 2001; 4: 997–1005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Castillo PE, Schoch S, Schmitz F, Sudhof TC, Malenka RC . RIM1alpha is required for presynaptic long-term potentiation. Nature 2002; 415: 327–330.

    Article  CAS  PubMed  Google Scholar 

  156. Lonart G, Schoch S, Kaeser PS, Larkin CJ, Sudhof TC, Linden DJ . Phosphorylation of RIM1alpha by PKA triggers presynaptic long-term potentiation at cerebellar parallel fiber synapses. Cell 2003; 115: 49–60.

    Article  CAS  PubMed  Google Scholar 

  157. Wang X, Hu B, Zimmermann B, Kilimann MW . Rim1 and rabphilin-3 bind Rab3-GTP by composite determinants partially related through N-terminal alpha -helix motifs. J Biol Chem 2001; 276: 32480–32488.

    Article  CAS  PubMed  Google Scholar 

  158. Bekkers JM, Stevens CF . Excitatory and inhibitory autaptic currents in isolated hippocampal neurons maintained in cell culture. Proc Natl Acad Sci USA 1991; 88: 7834–7838.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Geppert M, Goda Y, Stevens CF, Sudhof TC . The small GTP-binding protein Rab3A regulates a late step in synaptic vesicle fusion. Nature 1997; 387: 810–814.

    Article  CAS  PubMed  Google Scholar 

  160. Goda Y, Stevens CF . Two components of transmitter release at a central synapse. Proc Natl Acad Sci USA 1994; 91: 12942–12946.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Geppert M, Goda Y, Hammer RE, Li C, Rosahl TW, Stevens CF et al. Synaptotagmin I: a major Ca2+ sensor for transmitter release at a central synapse. Cell 1994; 79: 717–727.

    Article  CAS  PubMed  Google Scholar 

  162. Fernandez-Chacon R, Konigstorfer A, Gerber SH, Garcia J, Matos MF, Stevens CF et al. Synaptotagmin I functions as a calcium regulator of release probability. Nature 2001; 410: 41–49.

    Article  CAS  PubMed  Google Scholar 

  163. Castillo PE, Janz R, Sudhof TC, Tzounopoulos T, Malenka RC, Nicoll RA . Rab3A is essential for mossy fibre long-term potentiation in the hippocampus. Nature 1997; 388: 590–593.

    Article  CAS  PubMed  Google Scholar 

  164. Schluter OM, Schnell E, Verhage M, Tzonopoulos T, Nicoll RA, Janz R et al. Rabphilin knock-out mice reveal that rabphilin is not required for rab3 function in regulating neurotransmitter release. J Neurosci 1999; 19: 5834–5846.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Hosaka M, Hammer RE, Sudhof TC . A phospho-switch controls the dynamic association of synapsins with synaptic vesicles. Neuron 1999; 24: 377–387.

    Article  CAS  PubMed  Google Scholar 

  166. Lonart G . RIM1: an edge for presynaptic plasticity. Trends Neurosci 2002; 25: 329–332.

    Article  CAS  PubMed  Google Scholar 

  167. Spillane DM, Rosahl TW, Sudhof TC, Malenka RC . Long-term potentiation in mice lacking synapsins. Neuropharmacology 1995; 34: 1573–1579.

    Article  CAS  PubMed  Google Scholar 

  168. Lonart G, Janz R, Johnson KM, Sudhof TC . Mechanism of action of rab3A in mossy fiber LTP. Neuron 1998; 21: 1141–1150.

    Article  CAS  PubMed  Google Scholar 

  169. Hensbroek RA, Kamal A, Baars AM, Verhage M, Spruijt BM . Spatial, contextual and working memory are not affected by the absence of mossy fiber long-term potentiation and depression. Behav Brain Res 2003; 138: 215–223.

    Article  CAS  PubMed  Google Scholar 

  170. Huang YY, Kandel ER, Varshavsky L, Brandon EP, Qi M, Idzerda RL et al. A genetic test of the effects of mutations in PKA on mossy fiber LTP and its relation to spatial and contextual learning. Cell 1995; 83: 1211–1222.

    Article  CAS  PubMed  Google Scholar 

  171. Villacres EC, Wong ST, Chavkin C, Storm DR . Type I adenylyl cyclase mutant mice have impaired mossy fiber long-term potentiation. J Neurosci 1998; 18: 3186–3194.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Wu ZL, Thomas SA, Villacres EC, Xia Z, Simmons ML, Chavkin C et al. Altered behavior and long-term potentiation in type I adenylyl cyclase mutant mice. Proc Natl Acad Sci USA 1995; 92: 220–224.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Otto C, Kovalchuk Y, Wolfer DP, Gass P, Martin M, Zuschratter W et al. Impairment of mossy fiber long-term potentiation and associative learning in pituitary adenylate cyclase activating polypeptide type I receptor-deficient mice. J Neurosci 2001; 21: 5520–5527.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Sorensen JB, Fernandez-Chacon R, Sudhof TC, Neher E . Examining synaptotagmin 1 function in dense core vesicle exocytosis under direct control of Ca2+. J Gen Physiol 2003; 122: 265–276.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Sanes JR, Lichtman JW . Can molecules explain long-term potentiation?. Nat Neurosci 1999; 2: 597–604.

    Article  CAS  PubMed  Google Scholar 

  176. Lisman J, Lichtman JW, Sanes JR . LTP: perils and progress. Nat Rev Neurosci 2003; 4: 926–929.

    Article  CAS  PubMed  Google Scholar 

  177. Zhen M, Jin Y . The liprin protein SYD-2 regulates the differentiation of presynaptic termini in C. elegans. Nature 1999; 401: 371–375.

    CAS  PubMed  Google Scholar 

  178. Powell CM, Schoch S, Monteggia L, Barrot M, Matos MF, Feldmann N et al. The presynaptic active zone protein RIM1alpha is critical for normal learning and memory. Neuron 2004; 42: 143–153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We are grateful to Drs G Alvarez de Toledo, TC Südhof and L Tabares for advice and support and Drs A Lüthi, ML Montesinos and L Tabares for comments on the manuscript. Work in the RFC laboratory is supported in part by grants from the Spanish Ministry of Education and Science (BFI2001-4959-E, BFI2002-01686) and EMBO-Young Investigator Programme, and fellowships from the Spanish Foundation for Health Research (FIS) (PGJC) and the Spanish Ministry of Education and Science (PLC).

Author information

Authors and Affiliations

  1. Departamento de Fisiología Médica y Biofísica, Facultad de Medicina, Universidad de Sevilla, Avda. Sánchez-Pizjuán 4, Sevilla, Spain

    P García-Junco-Clemente, P Linares-Clemente & R Fernández-Chacón

Authors
  1. P García-Junco-Clemente
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P Linares-Clemente
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R Fernández-Chacón
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R Fernández-Chacón.

Rights and permissions

Reprints and permissions

About this article

Cite this article

García-Junco-Clemente, P., Linares-Clemente, P. & Fernández-Chacón, R. Active zones for presynaptic plasticity in the brain. Mol Psychiatry 10, 185–200 (2005). https://doi.org/10.1038/sj.mp.4001628

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4001628

Keywords

This article is cited by

Search

Advanced search

Quick links