GABA, Glycine, and Glutamate Co-Release at Developing Inhibitory Synapses

  • Deda C. GillespieEmail author
  • Karl Kandler


Neurobiologists have long classified synaptic phenotype by a single neurotransmitter released at that synapse. Research over the past two decades has made it clear, however, that the classification of neurons and synapses as purely GABAergic, or even as purely inhibitory or excitatory, is no longer valid. In this chapter we review evidence showing that inhibitory synapses co-release multiple inhibitory neurotransmitters, and that some classical inhibitory synapses also release excitatory neurotransmitters. As multiple transmitter release is particularly prevalent at immature synapses, we pay special attention to developmental plasticity in considering possible mechanisms and functions for release of these seemingly antagonistic neurotransmitters.


Synaptic Vesicle Glutamate Release Amacrine Cell Inhibitory Synapse Interaural Level Difference 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of Abbreviations




amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor


adenosine triphosphate


cochlear nucleus


gamma-aminobutyric acid


GABA (A) receptor


GABA (B) receptor


glutamic acid decarboxylase


glycine receptor


glycine transporter 2


inhibitory postsynaptic current


lateral superior olive


miniature inhibitory postsynaptic current


medial nucleus of the trapezoid body


miniature postsynaptic current


medial superior olive


N-methyl D-aspartic acid receptor


postnatal day n


superior paraolivary nucleus


vesicular GABA transporter


vesicular glutamate transporter 2


vesicular glutamate transporter 3


vesicular inhibitory amino acid transporter


  1. Aubrey KR, Rossi FM, Ruivo R, Alboni S, Bellenchi GC, Le Goff A, Gasnier B, Supplisson S (2007) The transporters GlyT2 and VIAAT cooperate to determine the vesicular glycinergic phenotype. J Neurosci 27:6273–6281PubMedGoogle Scholar
  2. Awatramani GB, Turecek R, Trussell LO (2005) Staggered development of GABAergic and glycinergic transmission in the MNTB. J Neurophysiol 93:819–828PubMedGoogle Scholar
  3. Banks MI, Smith PH (1992) Intracellular recordings from neurobiotin-labeled cells in brain slices of the rat medial nucleus of the trapezoid body. J Neurosci 12:2819–2837PubMedGoogle Scholar
  4. Behrend O, Brand A, Kapfer C, Grothe B (2002) Auditory response properties in the superior paraolivary nucleus of the gerbil. J Neurophysiol 87:2915–2928PubMedGoogle Scholar
  5. Ben-Ari Y, Khazipov R, Leinekugel X, Caillard O, Gaiarsa JL (1997) GABAA, NMDA and AMPA receptors: a developmentally regulated ‘me´nage a` trois’. Trends Neurosci 20:523–529Google Scholar
  6. Bergersen L, Ruiz A, Bjaalie JG, Kullmann DM, Gundersen V (2003) GABA and GABAA receptors at hippocampal mossy fibre synapses. Eur J Neurosci 18:931–941PubMedGoogle Scholar
  7. Beutner D, Moser T (2001) The presynaptic function of mouse cochlear inner hair cells during development of hearing. J Neurosci 21:4593–4599PubMedGoogle Scholar
  8. Bi GQ, Poo MM (1998) Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type. J Neurosci 18:10464–10472PubMedGoogle Scholar
  9. Blaesse P, Ehrhardt S, Friauf E, Nothwang HG (2005) Developmental pattern of three vesicular glutamate transporters in the rat superior olivary complex. Cell Tissue Res 320:33–50PubMedGoogle Scholar
  10. Borodinsky LN, Spitzer NC (2007) Activity-dependent neurotransmitter-receptor matching at the neuromuscular junction. Proc Natl Acad Sci USA. 104:335–340PubMedGoogle Scholar
  11. Boudreau JC, Tsuchitani C (1968) Binaural interaction in the cat superior olive S segment. J Neurophysiol 31:442–454PubMedGoogle Scholar
  12. Boulland JL, Qureshi T, Seal RP, Rafiki A, Gundersen V, Bergersen LH, Fremeau RT Jr, Edwards RH, Storm-Mathisen J, Chaudhry FA (2004) Expression of the vesicular glutamate transporters during development indicates the widespread corelease of multiple neurotransmitters. J Comp Neurol 480:264–280PubMedGoogle Scholar
  13. Caillard O, Ben-Ari Y, Gaiarsa JL (1999) Mechanisms of induction and expression of long-term depression at GABAergic synapses in the neonatal rat hippocampus. J Neurosci 19:7568–7577PubMedGoogle Scholar
  14. Cant NB, Casseday JH (1986) Projections from the anteroventral cochlear nucleus to the lateral and medial superior olivary nuclei. J Comp Neurol 247:457–476PubMedGoogle Scholar
  15. Carmignoto G, Vicini S (1992) Activity-dependent decrease in NMDA receptor responses during development of the visual cortex. Science 258:1007–1011PubMedGoogle Scholar
  16. Caspary DM, Finlayson PG (1991) Superior olivary complex: functional neuropharmacology of the principal cell types. In Neurobiology of hearing: the central auditory system (ed. RA Altschuler et al), 141–161Google Scholar
  17. Chang EH, Kotak VC, Sanes DH (2003) Long-term depression of synaptic inhibition is expressed postsynaptically in the developing auditory system. J Neurophysiol 90:1479–1488Google Scholar
  18. Charpier S, Behrends JC, Triller A, Faber DS, Korn H l (1995) “Latent” inhibitory connections become functional during activity-dependent plasticity. Proc Natl Acad Sci 92:117–120PubMedGoogle Scholar
  19. Chaudhry FA, Reimer RJ, Bellocchio EE, Danbolt NC, Osen KK, Edwards RH, Storm-Mathisen J (1998) The vesicular GABA transporter, VGAT, localizes to synaptic vesicles in sets of glycinergic as well as GABAergic neurons. J Neurosci 18:9733–9750PubMedGoogle Scholar
  20. Chery N, De Koninck Y (2000) GABA(B) receptors are the first target of released GABA at lamina I inhibitory synapses in the adult rat spinal cord. J Neurophysiol 84:1006–1011PubMedGoogle Scholar
  21. Contini M, Raviola E (2003) GABAergic synapses made by a retinal dopaminergic neuron. Proc Natl Acad Sci USA. 100:1358–1363PubMedGoogle Scholar
  22. Crair MC, Malenka RC (1995) A critical period for long-term potentiation at thalamocortical synapses. Nature 375:325–328PubMedGoogle Scholar
  23. Daniels RW, Collins CA, Chen K, Gelfand MV, Featherstone DE, DiAntonio A (2006) A single vesicular glutamate transporter is sufficient to fill a synaptic vesicle. Neuron 49:11–16PubMedGoogle Scholar
  24. Dehmel S, Kopp-Scheinpflug C, Dorrscheidt GJ, Rubsamen R (2002) Electrophysiological characterization of the superior paraolivary nucleus in the Mongolian gerbil. Hear Res 172:18–36PubMedGoogle Scholar
  25. Dugue GP, Dumoulin A, Triller A, Dieudonne S (2005) Target-dependent use of co-released inhibitory transmitters at central synapses. J Neurosci 25:6490–6498PubMedGoogle Scholar
  26. Eccles JC (1964) The physiology of synapses. Springer, BerlinGoogle Scholar
  27. Echteler, SM, Arjmand, E, Dallos, P (1989) Developmental alterations in the frequency map of the mammalian cochlea. Nature 341:147–149PubMedGoogle Scholar
  28. Ehrlich I, Lohrke S, Friauf E (1999) Shift from depolarizing to hyperpolarizing glycine action in rat auditory neurones is due to age-dependent Cl- regulation. J Physiol 520:121–137PubMedGoogle Scholar
  29. Feller MB, Wellis DP, Stellwagen D, Werblin FS, Shatz CJ (1996) Requirement for cholinergic synaptic transmission in the propagation of spontaneous retinal waves. Science 272:1182–1187PubMedGoogle Scholar
  30. Feng G, Tintrup H, Kirsch J, Nichol MC, Kuhse J, Betz H, Sanes JR (1998) Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity. Science 282:1321–1324PubMedGoogle Scholar
  31. Fremeau RT Jr, Burman J, Qureshi T, Tran CH, Proctor J, Johnson J, Zhang H, Sulzer D, Copenhagen DR, Storm-Mathisen J, Reimer RJ, Chaudhry FA, Edwards RH (2002) The identification of vesicular glutamate transporter 3 suggests novel modes of signaling by glutamate. Proc Natl Acad Sci USA. 99:14488–14493PubMedGoogle Scholar
  32. Friauf E, Aragon C, Lohrke S, Westenfelder B, Zafra F (1999) Developmental expression of the glycine transporter GLYT2 in the auditory system of rats suggests involvement in synapse maturation. J Comp Neurol 412:17–37PubMedGoogle Scholar
  33. Gabellec MM, Panzanelli P, Sassoe-Pognetto M, Lledo PM (2007) Synapse-specific localization of vesicular glutamate transporters in the rat olfactory bulb. Eur J Neurosci 25:1373–1383PubMedGoogle Scholar
  34. Gaiarsa JL, Caillard O, Ben-Ari Y (2002) Long-term plasticity at GABAergic and glycinergic synapses: mechanisms and functional significance. Tr Neurosci 25: 564–570Google Scholar
  35. Gillespie DC, Cihil K, Kandler K (2004) Developmental expression patterns of the vesicular glutamate transporters VGLUT1–3 in the auditory brainstem. Soc Nsci Abstr 947.12Google Scholar
  36. Gillespie DC, Kim G, Kandler K (2005) Inhibitory synapses in the developing auditory system are glutamatergic. Nat Neurosci 8:332–338PubMedGoogle Scholar
  37. Glendenning KK, Masterton RB, Baker BN, Wenthold RJ (1991) Acoustic chiasm. III: Nature, distribution, and sources of afferents to the lateral superior olive in the cat. J Comp Neurol 310:377–400PubMedGoogle Scholar
  38. Gras C, Herzog E, Bellenchi GC, Bernard V, Ravassard P, Pohl M, Gasnier B, Giros B, El Mestikawy S (2002) A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons. J Neurosci 22:5442–5451PubMedGoogle Scholar
  39. Gras C, Vinatier J, Amilhon B, Guerci A, Christov C, Ravassard P, Giros B, El Mestikawy S (2005) Developmentally regulated expression of VGLUT3 during early post-natal life. Neuropharmacology 49:901–911PubMedGoogle Scholar
  40. Gutierrez R (2000) Seizures induce simultaneous GABAergic and glutamatergic transmission in the dentate gyrus-CA3 system. J Neurophysiol 84:3088–3090PubMedGoogle Scholar
  41. Haas JS, Nowotny T, Abarbanel HD (2006) Spike-timing-dependent plasticity of inhibitory synapses in the entorhinal cortex. J Neurophysiol 96:3305–3313PubMedGoogle Scholar
  42. Haverkamp S, Wassle H (2004) Characterization of an amacrine cell type of the mammalian retina immunoreactive for vesicular glutamate transporter 3. J Comp Neurol 468:251–263PubMedGoogle Scholar
  43. Helfert RH, Juiz JM, Bledsoe SC Jr, Bonneau JM, Wenthold RJ, Altschuler RA (1992) Patterns of glutamate, glycine, and GABA immunolabeling in four synaptic terminal classes in the lateral superior olive of the guinea pig. J Comp Neurol 323:305–325PubMedGoogle Scholar
  44. Henkel CK, Brunso-Bechtold JK (1998) Calcium-binding proteins and GABA reveal spatial segregation of cell types within the developing lateral superior olivary nucleus of the ferret. Microsc Res Tech 41:234–245PubMedGoogle Scholar
  45. Herzog E, Gilchrist J, Gras C, Muzerelle A, Ravassard P, Giros B, Gaspar P, El Mestikawy S (2004) Localization of VGLUT3, the vesicular glutamate transporter type 3, in the rat brain. Neuroscience 123:983–1002PubMedGoogle Scholar
  46. Herzog E, Takamori S, Jahn R, Brose N, Wojcik SM (2006) Synaptic and vesicular co-localization of the glutamate transporters VGLUT1 and VGLUT2 in the mouse hippocampus. J Neurochem 99:1011–1018PubMedGoogle Scholar
  47. Hestrin S (1992) Developmental regulation of NMDA receptor-mediated synaptic currents at a central synapse. Nature 357:686–689PubMedGoogle Scholar
  48. Hooks BM, Chen C (2006) Distinct roles for spontaneous and visual activity in remodeling of the retinogeniculate synapse. Neuron 52:281–291PubMedGoogle Scholar
  49. Huberman AD, Speer CM, Chapman B (2006) Spontaneous retinal activity mediates development of ocular dominance columns and binocular receptive fields in v1. Neuron 52:247–254PubMedGoogle Scholar
  50. Hugel S, Schlichter R (2003) Convergent control of synaptic GABA release from rat dorsal horn neurones by adenosine and GABA autoreceptors. J Physiol 551:479–489PubMedGoogle Scholar
  51. Isaac JT, Crair MC, Nicoll RA, Malenka RC (1997) Silent synapses during development of thalamocortical inputs. Neuron 18:269–280PubMedGoogle Scholar
  52. Isaacson JS (1998) GABAB receptor-mediated modulation of presynaptic currents and excitatory transmission at a fast central synapse. J Neurophysiol 80:1571–1576PubMedGoogle Scholar
  53. Jo YH, Schlichter R (1999) Synaptic corelease of ATP and GABA in cultured spinal neurons. Nat Neurosc. 2:241–245Google Scholar
  54. Johnson J, Sherry DM, Liu X, Fremeau RT Jr, Seal RP, Edwards RH, Copenhagen DR (2004) Vesicular glutamate transporter 3 expression identifies glutamatergic amacrine cells in the rodent retina. J Comp Neurol 477:386–398PubMedGoogle Scholar
  55. Jonas P, Bischofberger J, Sandkuhler J. (1998) Corelease of two fast neurotransmitters at a central synapse. Science 281:419–424PubMedGoogle Scholar
  56. Juiz JM, Helfert RH, Bonneau JM, Wenthold RJ, Altschuler RA l (1996) Three classes of inhibitory amino acid terminals in the cochlear nucleus of the guinea pig. J Comp Neurol 373:11–26PubMedGoogle Scholar
  57. Kakizawa S, Yamasaki M, Watanabe M, Kano M (2000) Critical period for activity-dependent synapse elimination in developing cerebellum. J Neurosci 20:4954–4961PubMedGoogle Scholar
  58. Kandler K, Friauf E (1995) Development of glycinergic and glutamatergic synaptic transmission in the auditory brainstem of perinatal rats. J Neurosci 15:6890–6894PubMedGoogle Scholar
  59. Kano M, Rexhausen U, Dresse, J, Konnerth A (1992) Synaptic excitation produces a long-lasting rebound potentiation of inhibitory synaptic signals in cerebellar Purkinje cells. Nature 356:601–604PubMedGoogle Scholar
  60. Keller AF, Coull JA, Chery N, Poisbeau P, De Koninck Y (2001) Region-specific developmental specialization of GABA-glycine cosynapses in laminas I-II of the rat spinal dorsal horn. J Neurosci 21:7871–7880PubMedGoogle Scholar
  61. Kim GS, Kandler K (2003) Elimination and strengthening of glycinergic/GABAergic connections during tonotopic map formation. Nat Neurosci 6:282–290PubMedGoogle Scholar
  62. Kirsch J, Betz H (1998) Glycine-receptor activation is required for receptor clustering in spinal neurons. Nature 392:717–720PubMedGoogle Scholar
  63. Kneussel M, Brandstatter JH, Gasnier B, Feng G, Sanes JR, Betz H (2001) Gephyrin-independent clustering of postsynaptic GABA(A) receptor subtypes. Mol Cell Neurosci 17:973–982PubMedGoogle Scholar
  64. Kneussel M, Brandstatter JH, Laube B, Stahl S, Muller U, Betz H (1999) Loss of postsynaptic GABA(A) receptor clustering in gephyrin-deficient mice. J Neurosci 19:9289–9297PubMedGoogle Scholar
  65. Kolston J, Osen KK, Hackney CM, Ottersen OP, Storm-Mathisen J (1992) An atlas of glycine- and GABA-like immunoreactivity and colocalization in the cochlear nuclear complex of the guinea pig. Anat Embryol (Berl) 186:443–465Google Scholar
  66. Komatsu Y (1994) Age-dependent long-term potentiation of inhibitory synaptic transmission in rat visual cortex. J Neurosci 14:6488–6499PubMedGoogle Scholar
  67. Korada S, Schwartz IR (1999) Development of GABA, glycine, and their receptors in the auditory brainstem of gerbil: a light and electron microscopic study. J Comp Neurol 409:664–681PubMedGoogle Scholar
  68. Kotak VC, DiMattina C, Sanes DH (2001) GABA(B) and Trk receptor signaling mediates long-lasting inhibitory synaptic depression. J Neurophysiol 86:536–540Google Scholar
  69. Kotak VC, Korada S, Schwartz IR, Sanes DH (1998) A developmental shift from GABAergic to glycinergic transmission in the central auditory system. J Neurosci 18:4646–4655PubMedGoogle Scholar
  70. Kros CJ, Ruppersberg JP, Rusch A (1998) Expression of a potassium current in inner hair cells during development of hearing in mice. Nature 394:281–284PubMedGoogle Scholar
  71. Kulesza RJ Jr, Spirou GA, Berrebi AS (2003) Physiological response properties of neurons in the superior paraolivary nucleus of the rat. J Neurophysiol 89:2299–2312.PubMedGoogle Scholar
  72. Kullmann DM, Asztely F, Walker MC (2000) The role of mammalian ionotropic receptors in synaptic plasticity: LTP, LTD and epilepsy. Cell Mol Life Sci 57:1551–1561PubMedGoogle Scholar
  73. Kullmann PH, Kandler K (2001) Glycinergic/GABAergic synapses in the lateral superior olive are excitatory in neonatal C57B1/6 J mice. Brain Res Dev Brain Res 131:143–147PubMedGoogle Scholar
  74. Kullmann PH, Ene FA, Kandler K (2002) Glycinergic and GABAergic calcium responses in the developing lateral superior olive. Eur J Neurosci 15:1093–1104PubMedGoogle Scholar
  75. Leinekugel X, Medina I, Khalilov I, Ben-Ari Y, Khazipov R (1997) Ca2+ oscillations mediated by the synergistic excitatory actions of GABAA and NMDA receptors in the neonatal hippocampus. Neuron 18:243–255PubMedGoogle Scholar
  76. Levi S, Logan SM, Tovar KR, Craig AM (2004) Gephyrin is critical for glycine receptor clustering but not for the formation of functional GABAergic synapses in hippocampal neurons. J Neurosci 24:207–217PubMedGoogle Scholar
  77. Liao D, Zhang X, O’Brien R, Ehlers MD, Huganir RL (1999) Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons. Nat Neurosci 2:37–43PubMedGoogle Scholar
  78. Lien CC, Mu Y, Vargas-Caballero M, Poo MM (2006) Visual stimuli-induced LTD of GABAergic synapses mediated by presynaptic NMDA receptors. Nat Neurosci 9:372–380PubMedGoogle Scholar
  79. Lim R, Alvarez FJ, Walmsley B (2000) GABA mediates presynaptic inhibition at glycinergic synapses in a rat auditory brainstem nucleus. J Physiol 525:447–459PubMedGoogle Scholar
  80. Lippe WR (1994) Rhythmic spontaneous activity in the developing avian auditory system. J Neurosci 14:1486–1495PubMedGoogle Scholar
  81. Liu QR, Lopez-Corcuera B, Mandiyan S, Nelson H, Nelson N (1993) Cloning and expression of a spinal cord- and brain-specific glycine transporter with novel structural features. J Biol Chem 268:22802–22808PubMedGoogle Scholar
  82. McIntire SL, Reimer RJ, Schuske K, Edwards RH, Jorgensen EM (1997) Identification and characterization of the vesicular GABA transporter. Nature 389:870–876PubMedGoogle Scholar
  83. McLean HA, Caillard O, Ben-Ari Y, Gaiarsa JL (1996) Bidirectional plasticity expressed by GABAergic synapses in the neonatal rat hippocampus. J Physiol 496:471–477PubMedGoogle Scholar
  84. Meister M, Wong RO, Baylor DA, Shatz CJ (1991) Synchronous bursts of action potentials in ganglion cells of the developing mammalian retina. Science 252:939–943PubMedGoogle Scholar
  85. Moore MJ, Caspary DM (1983) Strychnine blocks binaural inhibition in lateral superior olivary neurons. J Neurosci 3:237–242PubMedGoogle Scholar
  86. Moss, SJ, Smart, TG (2001) Constructing inhibitory synapses. Nat Rev Neurosci 2:240–250PubMedGoogle Scholar
  87. Nabekura J, Katsurabayashi S, Kakazu Y, Shibata S, Matsubara A, Jinno S, Mizoguchi Y, Sasaki A, Ishibashi H (2004) Developmental switch from GABA to glycine release in single central synaptic terminals. Nat Neurosci 7:17–23PubMedGoogle Scholar
  88. Nugent FS, Penick EC, Kauer JA (2007) Opioids block long-term potentiation of inhibitory synapses. Nature 446:1086–10890PubMedGoogle Scholar
  89. O'Brien JA, Berger AJ (1999) Cotransmission of GABA and glycine to brain stem motoneurons. J Neurophysiol 82:1638–1641PubMedGoogle Scholar
  90. Oda Y, Charpier S, Murayama Y, et al (1995) Long-term potentiation of glycinergic inhibitory synaptic transmission. J Neurophysiol 74:1056–1074PubMedGoogle Scholar
  91. Oertel J, Villmann C, Kettenmann H, Kirchhoff F, Becker CM (2007) A novel glycine receptor beta subunit splice variant predicts an unorthodox transmembrane topology Assembly into heteromeric receptor complexes. J Biol Chem 282:2798–2807PubMedGoogle Scholar
  92. O'Malley DM, Masland RH (1989) Co-release of acetylcholine and gamma-aminobutyric acid by a retinal neuron. Proc Natl Acad Sci USA. 86:3414–3418PubMedGoogle Scholar
  93. O'Malley DM, Sandell JH, Masland RH (1992) Co-release of acetylcholine and GABA by the starburst amacrine cells. J Neurosci 12:1394–408PubMedGoogle Scholar
  94. Otis TS, De Koninck Y, Mody I (1994) Lasting potentiation of inhibition is associated with an increased number of gamma-aminobutyric acid type A receptors activated during miniature inhibitory postsynaptic currents. Proc Natl Acad Sci USA. 91:7698–7702PubMedGoogle Scholar
  95. Ottem EN, Godwin JG, Krishnan S, Petersen SL (2004) Dual-phenotype GABA/glutamate neurons in adult preoptic area: sexual dimorphism and function. J Neurosci 24:8097–8105PubMedGoogle Scholar
  96. Ottersen OP, Storm-Mathisen J (1984) Glutamate- and GABA-containing neurons in the mouse and rat brain, as demonstrated with a new immunocytochemical technique. J Comp Neurol 229:374–392PubMedGoogle Scholar
  97. Ottersen OP, Storm-Mathisen J, Somogyi P (1988) Colocalization of glycine-like and GABA-like immunoreactivities in Golgi cell terminals in the rat cerebellum: a postembedding light and electron microscopic study. Brain Res 450:342–353PubMedGoogle Scholar
  98. Ouardouz M, Sastry BR (2000) Mechanisms underlying LTP of inhibitory synaptic transmission in the deep cerebellar nuclei. J Neurophysiol 84:1414–1421PubMedGoogle Scholar
  99. Overstreet-Wadiche L, Bromberg DA, Bensen AL, Westbrook GL (2005) GABAergic signaling to newborn neurons in dentate gyrus. J Neurophysiol 94:4528–4532PubMedGoogle Scholar
  100. Owens DF, Kriegstein AR (2002) Is there more to GABA than synaptic inhibition? Nat Rev Neurosci 3:715–727PubMedGoogle Scholar
  101. Paarmann I, Schmitt B, Meyer B, Karas M, Betz H (2006) Mass spectrometric analysis of glycine receptor-associated gephyrin splice variants. J Biol Chem 281:34918–34925PubMedGoogle Scholar
  102. Piechotta K, Weth F, Harvey RJ, Friauf E (2001) Localization of rat glycine receptor alpha1 and alpha2 subunit transcripts in the developing auditory brainstem. J Comp Neurol 438:336–352PubMedGoogle Scholar
  103. Rabacchi S, Bailly Y, Delhaye-Bourchaud N, Mariani J (1992) Involvement of the N-methyl D-aspartate (NMDA) receptor in synapse elimination during cerebellar development. Science 256:1823–1825PubMedGoogle Scholar
  104. Represa A, Ben-Ari Y (2005) Trophic actions of GABA on neuronal development. Trends Neurosci 28:278–283PubMedGoogle Scholar
  105. Rusakov DA, Kullmann DM (1998) Extrasynaptic glutamate diffusion in the hippocampus: ultrastructural constraints, uptake, and receptor activation. J Neurosci 18:3158–3170PubMedGoogle Scholar
  106. Russier M, Kopysova IL, Ankri N, Ferrand N, Debanne D (2002) GABA and glycine co-release optimizes functional inhibition in rat brainstem motoneurons in vitro. J Physiol 541:123–137PubMedGoogle Scholar
  107. Sagne C, El Mestikawy S, Isambert MF, Hamon M, Henry JP, Giros B, Gasnier B (1997) Cloning of a functional vesicular GABA and glycine transporter by screening of genome databases. FEBS Lett 417:177–183PubMedGoogle Scholar
  108. Sandler R, Smith AD (1991) Coexistence of GABA and glutamate in mossy fiber terminals of the primate hippocampus: an ultrastructural study. J Comp Neurol 303:177–192PubMedGoogle Scholar
  109. Sanes DH, Rubel EW (1988) The ontogeny of inhibition and excitation in the gerbil lateral superior olive. J Neurosci 8:682–700PubMedGoogle Scholar
  110. Sanes DH, Siverls V (1991) Development and specificity of inhibitory terminal arborizations in the central nervous system. J Neurobiol 22:837–854PubMedGoogle Scholar
  111. Schafer MK, Varoqui H, Defamie N, Weihe E, Erickson JD (2002) Molecular cloning and functional identification of mouse vesicular glutamate transporter 3 and its expression in subsets of novel excitatory neurons. J Biol Chem 277:50734–50748PubMedGoogle Scholar
  112. Seal RP, Edwards RH. (2006) The diverse roles of vesicular glutamate transporter 3. Handb Exp Pharmacol (175):137–150Google Scholar
  113. Seddik R, Schlichter R, Trouslard J (2007) Corelease of GABA/glycine in lamina-X of the spinal cord of neonatal rats. Neuroreport 18:1025–1029PubMedGoogle Scholar
  114. Smith AJ, Owens S, Forsythe ID (2000) Characterisation of inhibitory and excitatory postsynaptic currents of the rat medial superior olive. J Physiol 529:681–698PubMedGoogle Scholar
  115. Smith PH, Joris PX, Carney LH, Yin TCT (1991) Projections of physiologically characterized globular bushy cell axons from the cochlear nucleus of the cat. J Comp Neurol 304:387–407PubMedGoogle Scholar
  116. Somogyi J (2006) Functional significance of co-localization of GABA and Glu in nerve terminals: a hypothesis. Curr Top Med Chem 6:969–973PubMedGoogle Scholar
  117. Somogyi J, Baude A, Omori Y, Shimizu H, El Mestikawy S, Fukaya M, Shigemoto R, Watanabe M, Somogyi P (2004) GABAergic basket cells expressing cholecystokinin contain vesicular glutamate transporter type 3 (VGLUT3) in their synaptic terminals in hippocampus and isocortex of the rat. Eur J Neurosci 19:552–569PubMedGoogle Scholar
  118. Spike RC, Watt C, Zafra F, Todd AJ (1997) An ultrastructural study of the glycine transporter GLYT2 and its association with glycine in the superficial laminae of the rat spinal dorsal horn. Neuroscience 77:543–551PubMedGoogle Scholar
  119. Stornetta RL, Rosin DL, Simmons JR, McQuiston TJ, Vujovic N, Weston MC, Guyenet PG (2005) Coexpression of vesicular glutamate transporter-3 and gamma-aminobutyric acidergic markers in rat rostral medullary raphe and intermediolateral cell column. J Comp Neurol 492:477–494PubMedGoogle Scholar
  120. Takamori S, Malherbe P, Broger C, Jahn R (2002) Molecular cloning and functional characterization of human vesicular glutamate transporter 3. EMBO Rep 3:798–803PubMedGoogle Scholar
  121. Takamori S, Holt M, Stenius K, Lemke EA, Gronborg M, Riedel D, Urlaub H, Schenck S, Brugger B, Ringler P, Muller SA, Rammner B, Grater F, Hub JS, De Groot BL, Mieskes G, Moriyama Y, Klingauf J, Grubmuller H, Heuser J, Wieland F, Jahn R (2006) Molecular anatomy of a trafficking organelle. Cell 127:831–846PubMedGoogle Scholar
  122. Tkatch T, Baranauskas G, Surmeier DJ (1998) Basal forebrain neurons adjacent to the globus pallidus coexpress GABAergic and cholinergic marker mRNAs. Neuroreport 9:1935–1939PubMedGoogle Scholar
  123. Todd AJ (1991) Immunohistochemical evidence that acetylcholine and glycine exist in different populations of GABAergic neurons in lamina III of rat spinal dorsal horn. Neuroscience 44:741–746PubMedGoogle Scholar
  124. Todd AJ, Sullivan AC (1990) Light microscope study of the coexistence of GABA-like and glycine-like immunoreactivities in the spinal cord of the rat. J Comp Neurol 296:496–505PubMedGoogle Scholar
  125. Triller A, Cluzeaud F, Korn H (1987) gamma-Aminobutyric acid-containing terminals can be apposed to glycine receptors at central synapses. J Cell Biol 104:947–956PubMedGoogle Scholar
  126. Tsen G, Williams B, Allaire P, Zhoru YD, Ikonomov O, Kondova I, Jacob MH (2000) Receptors with opposing functions are in postsynaptic microdomains under one presynaptic terminal. Nat Neurosci 3:126–132Google Scholar
  127. Turecek R, Trussell LO (2001) Presynaptic glycine receptors enhance transmitter release at a mammalian central synapse. Nature 411:587–590PubMedGoogle Scholar
  128. Turecek R, Trussell LO (2002) Reciprocal developmental regulation of presynaptic ionotropic receptors. Proc Natl Acad Sci USA. 99:13884–13889PubMedGoogle Scholar
  129. Vaney DI, Young HM (1988) GABA-like immunoreactivity in cholinergic amacrine cells of the rabbit retina. Brain Res. 438:369–373PubMedGoogle Scholar
  130. Walker MC, Ruiz A, Kullmann DM (2001) Monosynaptic GABAergic signaling from dentate to CA3 with a pharmacological and physiological profile typical of mossy fiber synapses. Neuron 29:703–715PubMedGoogle Scholar
  131. Wang CT, Blankenship AG, Anishchenko A, Elstrott J, Fikhman M, Nakanishi S, Feller MB (2007) GABA(A) receptor-mediated signaling alters the structure of spontaneous activity in the developing retina. J Neurosci 27:9130–9140PubMedGoogle Scholar
  132. Wang, JH, Stelzer, A (1996) Shared calcium signalling pathways in the induction of long-term potentiation and synaptic disinhibition in CA1 pyramidal cell dendrites. J Neurophysiol 75:1687–1702PubMedGoogle Scholar
  133. Wentzel PR, De Zeeuw CI, Holstege JC, Gerrits NM (1993) Colocalization of GABA and glycine in the rabbit oculomotor nucleus. Neurosci Lett 164:25–29PubMedGoogle Scholar
  134. Wojcik SM, Katsurabayashi S, Guillemin I, Friauf E, Rosenmund C, Brose N, Rhee JS (2006) A shared vesicular carrier allows synaptic corelease of GABA and glycine. Neuron 50:575–587PubMedGoogle Scholar
  135. Woodin MA, Ganguly K, Poo MM (2003) Coincident pre- and postsynaptic activity modifies GABAergic synapses by postsynaptic changes in Cl- transporter activity. Neuron 39:807–820PubMedGoogle Scholar
  136. Wu SH, Kelly JB (1992) Synaptic pharmacology of the superior olivary complex studied in mouse brain slice. J Neurosci 12:3084–3097PubMedGoogle Scholar
  137. Wulle I, Wagner HJ. (1990) GABA and tyrosine hydroxylase immunocytochemistry reveal different patterns of colocalization in retinal neurons of various vertebrates. J Comp Neurol 296:173–178PubMedGoogle Scholar
  138. Xu J, Mashimo T, Sudhof TC (2007) Synaptotagmin-1, -2, and -9: Ca(2+) sensors for fast release that specify distinct presynaptic properties in subsets of neurons. Neuron 54:567–581PubMedGoogle Scholar
  139. Zafra F, Gomeza J, Olivares L, Aragon C, Gimenez C (1995) Regional distribution and developmental variation of the glycine transporters GLYT1 and GLYT2 in the rat CNS. Eur J Neurosci 7:1342–1352PubMedGoogle Scholar
  140. Zheng JJ, Lee S, Zhou ZJ (2004) A developmental switch in the excitability and function of the starburst network in the mammalian retina. Neuron 44:851–864PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of PsychologyNeuroscience & Behaviour, McMaster UniversityHamiltonCanada
  2. 2.Department of Otolaryngology and NeurobiologySchool of Medicine, University of PittsburghPittsburghUSA

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