Postsynaptic Determinants of Inhibitory Transmission at Mixed GABAergic/Glycinergic Synapses

  • Stéphane DieudonnéEmail author
  • Marco Alberto Diana


In the vertebrate central nervous system, ionotropic inhibition is mediated by two neurotransmitters: GABA and glycine. While inhibitory neurons of the forebrain release mainly GABA, both neurotransmitters coexist in most structures of the hindbrain. More specifically, a majority of hindbrain inhibitory neurons contain both GABA and glycine that accumulate in the same vesicle and are co-released. On the postsynaptic side, GABA and glycine activate separate chloride-permeant ionotropic receptors that display similar biophysical properties. We review here the distribution and organization of inhibitory co-transmission, with an emphasis on the postsynaptic side of the synapse. We show that very different types of functional organization have been adopted by mixed inhibitory circuits. However one rule is always preserved: the GABAergic and glycinergic components of mixed inhibitory synapses display different decay kinetics. GABAA receptor kinetics are determined by the combination of a rich variety of subunits. In contrast glycinergic receptors are assembled from a small number of subunits and most adult neurons may express the same receptor type. Accumulating evidence suggests that the kinetics of glycine synaptic currents could be determined and modulated in an activity dependant manner, through various mechanisms. In conclusion we propose that tunable glycinergic inhibition timecourse may optimize rate-coding circuits of the hindbrain whereas forebrain coding through oscillations and synchrony may benefit from the rigid yet diverse subunit combination of GABAA receptors.


GABAA Receptor Decay Kinetic Granule Cell Layer Golgi Cell Dorsal Cochlear Nucleus 
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.



We thank Dr. Eric Schwartz for critically reading the manuscript. This work was supported by grant ANR-05-neur-030-03, by the CNRS and the INSERM.


  1. 1.
    Aguayo LG, van Zundert B, Tapia JC, Carrasco MA, Alvarez FJ (2004) Changes on the properties of glycinergic receptors during neuronal development. Brain Res Rev 47:33–45PubMedGoogle Scholar
  2. 2.
    Akagi H, Miledi R (1988) Heterogeneity of glycinergic receptors and their messenger RNAs in rat brain and spinal cord. Science 242:270–273PubMedGoogle Scholar
  3. 3.
    Akagi T, Kaneda M, Ishii K, Hashikawa T (2001) Differential subcellular localization of zinc in the rat retina. J Histochem Cytochem 49:87–96PubMedGoogle Scholar
  4. 4.
    Alibardi L (2003) Ultrastructural distribution of glycinergic and GABAergic neurons and axon terminals in the rat dorsal cochlear nucleus, with emphasis on granule cell areas. J Anat 203:31–56PubMedGoogle Scholar
  5. 5.
    Armsen W, Himmel B, Betz H, Eulenburg V (2007) The C-terminal PDZ-ligand motif of the neuronal glycine transporter GlyT2 is required for efficient synaptic localization. Mol Cell Neurosci 36:369–380PubMedGoogle Scholar
  6. 6.
    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
  7. 7.
    Auger C, Marty A (1997) Heterogeneity of functional synaptic parameters among single release sites. Neuron 19:139–150PubMedGoogle Scholar
  8. 8.
    Awatramani GB, Turecek R, Trussell LO (2005) Staggered development of GABAergic and glycinergic transmission in the MNTB. J Neurophysiol 93:819–828PubMedGoogle Scholar
  9. 9.
    Balakrishnan V, Trussell LO (2008) Synaptic inputs to granule cells of the dorsal cochlear nucleus. J Neurophysiol 99:208–219PubMedGoogle Scholar
  10. 10.
    Barbour B, Hausser M (1997) Intersynaptic diffusion of neurotransmitter. TINS 20:377–384PubMedGoogle Scholar
  11. 11.
    Barker JL, Ransom BR (1978) Amino acid pharmacology of mammalian central neurones grown in tissue culture. J Physiol 280:331–354PubMedGoogle Scholar
  12. 12.
    Baurle J, Grusser-Cornehls U (1997) Differential number of glycine- and GABA-immunopositive neurons and terminals in the deep cerebellar nuclei of normal and Purkinje cell degeneration mutant mice. J Comp Neur 382:443–458PubMedGoogle Scholar
  13. 13.
    Beato M, Groot-Kormelink PJ, Colquhoun D, Sivilotti LG (2002) Openings of the rat recombinant alpha 1 homomeric glycinergic receptor as a function of the number of agonist molecules bound. J Gen Physiol 119:443–466PubMedGoogle Scholar
  14. 14.
    Beato M, Groot-Kormelink PJ, Colquhoun D, Sivilotti LG (2004) The activation mechanism of alpha1 homomeric glycinergic receptors. J Neurosci 24:895–906PubMedGoogle Scholar
  15. 15.
    Becker CM, Hoch W, Betz H (1988) Glycinergic receptor heterogeneity in rat spinal cord during postnatal development. EMBO 7:3717–3726Google Scholar
  16. 16.
    Becker CM, Betz H, Schroder H (1993) Expression of inhibitory glycinergic receptors in postnatal rat cerebral cortex. Brain Res 606:220–226PubMedGoogle Scholar
  17. 17.
    Betz H, Kuhse J, Schmieden V, Malosio ML, Langosch D, Prior P, Schmitt B, Kirsch J (1991) How to build a glycinergic postsynaptic membrane. J Cell Sci 15:23–25Google Scholar
  18. 18.
    Birinyi A, Parker D, Antal M, Shupliakov O (2001) Zinc co-localizes with GABA and glycine in synapses in the lamprey spinal cord. J Comp Neurol 433:208–221PubMedGoogle Scholar
  19. 19.
    Bohlhalter S, Mohler H, Fritschy JM (1994) Inhibitory neurotransmission in rat spinal cord: colocalization of glycine- and GABAA-receptors at GABAergic synaptic contacts demonstrated by triple immunofluorescence staining. Brain Res 642:59–69PubMedGoogle Scholar
  20. 20.
    Bormann J (2000) The 'ABC' of GABAergic receptors. TIPS 21:16–19PubMedGoogle Scholar
  21. 21.
    Bowery NG, Smart TG (2006) GABA and glycine as neurotransmitters: a brief history. B J Pharmacol 147 Suppl 1:S109–119Google Scholar
  22. 22.
    Brand A, Behrend O, Marquardt T, McAlpine D, Grothe B (2002) Precise inhibition is essential for microsecond interaural time difference coding. Nature 417:543–547PubMedGoogle Scholar
  23. 23.
    Brickley SG, Cull-Candy SG, Farrant M (1996) Development of a tonic form of synaptic inhibition in rat cerebellar granule cells resulting from persistent activation of GABAA receptors. J Physiol 497:753–759PubMedGoogle Scholar
  24. 24.
    Burgard EC, Tietz EI, Neelands TR, Macdonald RL (1996) Properties of recombinant gamma-aminobutyric acid A receptor isoforms containing the alpha 5 subunit subtype. Mol pharmacol 50:119–127PubMedGoogle Scholar
  25. 25.
    Burger PM, Hell J, Mehl E, Krasel C, Lottspeich F, Jahn R (1991) GABA and glycine in synaptic vesicles: storage and transport characteristics. Neuron 7:287–293PubMedGoogle Scholar
  26. 26.
    Burnstock G (1976) Do some nerve cells release more than one transmitter? Neurosci 1:239–248Google Scholar
  27. 27.
    Burzomato V, Beato M, Groot-Kormelink PJ, Colquhoun D, Sivilotti LG (2004) Single-channel behavior of heteromeric alpha1beta glycinergic receptors: an attempt to detect a conformational change before the channel opens. J Neurosci 24:10924–10940PubMedGoogle Scholar
  28. 28.
    Chattipakorn SC, McMahon LL (2002) Pharmacological characterization of glycine-gated chloride currents recorded in rat hippocampal slices. J Neurophysiol 87:1515–1525PubMedGoogle Scholar
  29. 29.
    Chattipakorn SC, McMahon LL (2003) Strychnine-sensitive glycinergic receptors depress hyperexcitability in rat dentate gyrus. J Neurophysiol 89:1339–1342PubMedGoogle Scholar
  30. 30.
    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
  31. 31.
    Chen S, Hillman DE (1993) Colocalization of neurotransmitters in the deep cerebellar nuclei. J Neurocytol 22:81–91PubMedGoogle Scholar
  32. 32.
    Chery N, de Koninck Y (1999) Junctional versus extrajunctional glycine and GABA(A) receptor-mediated IPSCs in identified lamina I neurons of the adult rat spinal cord. J Neurosci 19:7342–7355PubMedGoogle Scholar
  33. 33.
    Christensen H, Fykse EM, Fonnum F (1991) Inhibition of gamma-aminobutyrate and glycine uptake into synaptic vesicles. Eur J Pharmacol 207:73–79PubMedGoogle Scholar
  34. 34.
    Cole TB, Robbins CA, Wenzel HJ, Schwartzkroin PA, Palmiter RD (2000) Seizures and neuronal damage in mice lacking vesicular zinc. Epilepsy Res 39:153–169PubMedGoogle Scholar
  35. 35.
    Danglot L, Rostaing P, Triller A, Bessis A (2004) Morphologically identified glycinergic synapses in the hippocampus. Mol Cell Neurosci 27:394–403PubMedGoogle Scholar
  36. 36.
    Danober L, Pape HC (1998) Strychnine-sensitive glycine responses in neurons of the lateral amygdala: an electrophysiological and immunocytochemical characterization. Neurosci 85:427–441Google Scholar
  37. 37.
    Danscher G, Jo SM, Varea E, Wang Z, Cole TB, Schroder HD (2001) Inhibitory zinc-enriched terminals in mouse spinal cord. Neurosci 105:941–947Google Scholar
  38. 38.
    Danscher G, Stoltenberg M (2005) Zinc-specific autometallographic in vivo selenium methods: tracing of zinc-enriched (ZEN) terminals, ZEN pathways, and pools of zinc ions in a multitude of other ZEN cells. J Histochem Cytochem 53:141–153PubMedGoogle Scholar
  39. 39.
    Darstein M, Loschmann PA, Knorle R, Feuerstein TJ (1997) Strychnine-sensitive glycinergic receptors inducing [3H]-acetylcholine release in rat caudatoputamen: a new site of action of ethanol? Naunyn-Schmiedeberg’s Arch Pharmacol 356:738–745Google Scholar
  40. 40.
    Darstein M, Landwehrmeyer GB, Kling C, Becker CM, Feuerstein TJ (2000) Strychnine-sensitive glycinergic receptors in rat caudatoputamen are expressed by cholinergic interneurons. Neurosci 96:33–39Google Scholar
  41. 41.
    De Saint Jan D, David-Watine B, Korn H, Bregestovski P (2001) Activation of human alpha1 and alpha2 homomeric glycinergic receptors by taurine and GABA. J Physiol 535:741–755PubMedGoogle Scholar
  42. 42.
    Dean I, Robertson SJ, Edwards FA (2003) Serotonin drives a novel GABAergic synaptic current recorded in rat cerebellar purkinje cells: a Lugaro cell to Purkinje cell synapse. J Neurosci 23:4457–4469PubMedGoogle Scholar
  43. 43.
    Deleuze C, Alonso G, Lefevre IA, Duvoid-Guillou A, Hussy N (2005) Extrasynaptic localization of glycinergic receptors in the rat supraoptic nucleus: further evidence for their involvement in glia-to-neuron communication. Neurosci 133:175–183Google Scholar
  44. 44.
    Diamond J, Roper S (1973) Analysis of Mauthner cell responses to iontophoretically delivered pulses of GABA, glycine and L-glutamate. J Physiol 232:113–128PubMedGoogle Scholar
  45. 45.
    Dieudonné S (1995) Glycinergic synaptic currents in Golgi cells of the rat cerebellum. PNAS 92:1441–1445PubMedGoogle Scholar
  46. 46.
    Dieudonné S, Dumoulin A (2000) Serotonin-driven long-range inhibitory connections in the cerebellar cortex. J Neurosci 20:1837–1848PubMedGoogle Scholar
  47. 47.
    Draguhn A, Verdorn TA, Ewert M, Seeburg PH, Sakmann B (1990) Functional and molecular distinction between recombinant rat GABAA receptor subtypes by Zn2+. Neuron 5:781–788PubMedGoogle Scholar
  48. 48.
    Dudeck O, Lubben S, Eipper S, Knorle R, Kirsch M, Honegger J, Zentner J, Feuerstein TJ (2003) Evidence for strychnine-sensitive glycinergic receptors in human amygdala. Naunyn-Schmiedeberg’s Arch Pharmacol 368:181–187Google Scholar
  49. 49.
    Dugue GP, Dumoulin A, Triller A, Dieudonné S (2005) Target-dependent use of co-released inhibitory transmitters at central synapses. J Neurosci 25:6490–6498PubMedGoogle Scholar
  50. 50.
    Dumoulin A, Rostaing P, Bedet C, Levi S, Isambert MF, Henry JP, Triller A, Gasnier B (1999) Presence of the vesicular inhibitory amino acid transporter in GABAergic and glycinergic synaptic terminal boutons. J Cell Sci 112:811–823PubMedGoogle Scholar
  51. 51.
    Dumoulin A, Triller A, Dieudonné S (2001) IPSC kinetics at identified GABAergic and mixed GABAergic and glycinergic synapses onto cerebellar Golgi cells. J Neurosci 21:6045–6057PubMedGoogle Scholar
  52. 52.
    Ebihara S, Takishima T, Shirasaki T, Akaike N (1992) Regional variation of excitatory and inhibitory amino acid-induced responses in rat dissociated CNS neurons. Neurosci Res 14:61–71PubMedGoogle Scholar
  53. 53.
    Ericson M, Molander A, Stomberg R, Soderpalm B (2006) Taurine elevates dopamine levels in the rat nucleus accumbens; antagonism by strychnine. Eur J Neurosci 23:3225–3229PubMedGoogle Scholar
  54. 54.
    Eto K, Arimura Y, Nabekura J, Noda M, Ishibashi H (2007) The effect of zinc on glycinergic inhibitory postsynaptic currents in rat spinal dorsal horn neurons. Brain Res 1161:11–20PubMedGoogle Scholar
  55. 55.
    Faber DS, Korn H (1980) Single-shot channel activation accounts for duration of inhibitory postsynaptic potentials in a central neuron. Science 208:612–615PubMedGoogle Scholar
  56. 56.
    Fisher JL (2002) A histidine residue in the extracellular N-terminal domain of the GABA(A) receptor alpha5 subunit regulates sensitivity to inhibition by zinc. Neuropharmacol 42:922–928Google Scholar
  57. 57.
    Fisher JL, Macdonald RL (1998) The role of an alpha subtype M2-M3 His in regulating inhibition of GABAA receptor current by zinc and other divalent cations. J Neurosci 18:2944–2953PubMedGoogle Scholar
  58. 58.
    Flint AC, Liu X, Kriegstein AR (1998) Nonsynaptic glycinergic receptor activation during early neocortical development. Neuron 20:43–53PubMedGoogle Scholar
  59. 59.
    Frazao R, Nogueira MI, Wassle H (2007) Colocalization of synaptic GABA(C)-receptors with GABA (A)-receptors and glycine-receptors in the rodent central nervous system. Cell Tiss Res 330:1–15Google Scholar
  60. 60.
    Fucile S, de Saint Jan D, David-Watine B, Korn H, Bregestovski P (1999) Comparison of glycine and GABA actions on the zebrafish homomeric glycinergic receptor. J Physiol 517:369–383PubMedGoogle Scholar
  61. 61.
    Fucile S, De Saint Jan D, de Carvalho LP, Bregestovski P (2000) Fast potentiation of glycinergic receptor channels of intracellular calcium in neurons and transfected cells. Neuron 28:571–583PubMedGoogle Scholar
  62. 62.
    Galarreta M, Hestrin S (1997) Properties of GABAA receptors underlying inhibitory synaptic currents in neocortical pyramidal neurons. J Neurosci 17:7220–7227PubMedGoogle Scholar
  63. 63.
    Gao BX, Stricker C, Ziskind-Conhaim L (2001) Transition from GABAergic to glycinergic synaptic transmission in newly formed spinal networks. J Neurophysiol 86:492–502PubMedGoogle Scholar
  64. 64.
    Geerlings A, Nunez E, Lopez-Corcuera B, Aragon C (2001) Calcium- and syntaxin 1-mediated trafficking of the neuronal glycine transporter GLYT2. J Biol Chem 276:17584–17590.PubMedGoogle Scholar
  65. 65.
    Geiman EJ, Zheng W, Fritschy JM, Alvarez FJ (2002) Glycine and GABA(A) receptor subunits on Renshaw cells: relationship with presynaptic neurotransmitters and postsynaptic gephyrin clusters. J Comp Neurol 444:275–289PubMedGoogle Scholar
  66. 66.
    Gentet LJ, Clements JD (2002) Binding site stoichiometry and the effects of phosphorylation on human alpha1 homomeric glycinergic receptors. J Physiol 544:97–106PubMedGoogle Scholar
  67. 67.
    Geurts FJ, De Schutter E, Dieudonné S (2003) Unraveling the cerebellar cortex: cytology and cellular physiology of large-sized interneurons in the granular layer. Cerebellum 2:290–299PubMedGoogle Scholar
  68. 68.
    Ghavanini AA, Mathers DA, Puil E (2005) Glycinergic inhibition in thalamus revealed by synaptic receptor blockade. Neuropharmacol 49:338–349Google Scholar
  69. 69.
    Ghavanini AA, Mathers DA, Kim HS, Puil E (2006) Distinctive glycinergic currents with fast and slow kinetics in thalamus. J Neurophysiol 95:3438–3448PubMedGoogle Scholar
  70. 70.
    Gonzalez-Forero D, Alvarez FJ (2005) Differential postnatal maturation of GABAA, glycinergic receptor, and mixed synaptic currents in Renshaw cells and ventral spinal interneurons. J Neurosci 25:2010–2023PubMedGoogle Scholar
  71. 71.
    Hamann M, Rossi DJ, Attwell D (2002) Tonic and spillover inhibition of granule cells control information flow through cerebellar cortex. Neuron 33:625–633PubMedGoogle Scholar
  72. 72.
    Harvey RJ, Thomas P, James CH, Wilderspin A, Smart TG (1999) Identification of an inhibitory Zn2+ binding site on the human glycinergic receptor alpha1 subunit. J Physiol 520 Pt 1:53–64Google Scholar
  73. 73.
    Hirzel K, Muller U, Latal AT, Hulsmann S, Grudzinska J, Seeliger MW, Betz H, Laube B (2006) Hyperekplexia phenotype of glycinergic receptor alpha1 subunit mutant mice identifies Zn(2+) as an essential endogenous modulator of glycinergic neurotransmission. Neuron 52:679–690PubMedGoogle Scholar
  74. 74.
    Horiuchi M, Loebrich S, Brandstaetter JH, Kneussel M, Betz H (2005) Cellular localization and subcellular distribution of Unc-33-like protein 6, a brain-specific protein of the collapsin response mediator protein family that interacts with the neuronal glycine transporter 2. J Neurochem 94:307–315PubMedGoogle Scholar
  75. 75.
    Hussy N, Deleuze C, Pantaloni A, Desarmenien MG, Moos F (1997) Agonist action of taurine on glycinergic receptors in rat supraoptic magnocellular neurones: possible role in osmoregulation. J Physiol 502:609–621PubMedGoogle Scholar
  76. 76.
    Hussy N, Bres V, Rochette M, Duvoid A, Alonso G, Dayanithi G, Moos FC (2001) Osmoregulation of vasopressin secretion via activation of neurohypophysial nerve terminals glycinergic receptors by glial taurine. J Neurosci 21:7110–7116PubMedGoogle Scholar
  77. 77.
    Ito S, Cherubini E (1991) Strychnine-sensitive glycine responses of neonatal rat hippocampal neurones. J Physiol 440:67–83PubMedGoogle Scholar
  78. 78.
    Jiang Z, Krnjevic K, Wang F, Ye JH (2004) Taurine activates strychnine-sensitive glycinergic receptors in neurons freshly isolated from nucleus accumbens of young rats. J Neurophysiol 91:248–257PubMedGoogle Scholar
  79. 79.
    Jin H, Wu H, Osterhaus G, Wei J, Davis K, Sha D, Floor E, Hsu CC, Kopke RD, Wu JY (2003) Demonstration of functional coupling between gamma -aminobutyric acid (GABA) synthesis and vesicular GABA transport into synaptic vesicles. PNAS 100:4293–4298PubMedGoogle Scholar
  80. 80.
    Jonas P, Bischofberger J, Sandkuhler J (1998) Corelease of two fast neurotransmitters at a central synapse. Science 281:419–424PubMedGoogle Scholar
  81. 81.
    Jones MV, Westbrook GL (1995) Desensitized states prolong GABAA channel responses to brief agonist pulses. Neuron 15:181–191PubMedGoogle Scholar
  82. 82.
    Jones MV, Sahara Y, Dzubay JA, Westbrook GL (1998) Defining affinity with the GABAA receptor. J Neurosci 18:8590–8604PubMedGoogle Scholar
  83. 83.
    Jones MV, Jonas P, Sahara Y, Westbrook GL (2001) Microscopic kinetics and energetics distinguish GABA(A) receptor agonists from antagonists. Biophys J 81:2660–2670PubMedGoogle Scholar
  84. 84.
    Kaneda M, Farrant M, Cull-Candy SG (1995) Whole-cell and single-channel currents activated by GABA and glycine in granule cells of the rat cerebellum. J Physiol 485:419–435PubMedGoogle Scholar
  85. 85.
    Kaneda M, Ishii K, Akagi T, Tatsukawa T, Hashikawa T (2005) Endogenous zinc can be a modulator of glycinergic signaling pathway in the rat retina. J Molec Histol 36:179–185Google Scholar
  86. 86.
    Katsurabayashi S, Kubota H, Higashi H, Akaike N, Ito Y (2004) Distinct profiles of refilling of inhibitory neurotransmitters into presynaptic terminals projecting to spinal neurones in immature rats. J Physiol 560:469–478PubMedGoogle Scholar
  87. 87.
    Kawa K (2003) Glycinergic receptors and glycinergic synaptic transmission in the deep cerebellar nuclei of the rat: a patch-clamp study. J Neurophysiol 90:3490–3500PubMedGoogle Scholar
  88. 88.
    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
  89. 89.
    Keller AF, Breton JD, Schlichter R, Poisbeau P (2004) Production of 5alpha-reduced neurosteroids is developmentally regulated and shapes GABA(A) miniature IPSCs in lamina II of the spinal cord. J Neurosci 24:907–915PubMedGoogle Scholar
  90. 90.
    Knoflach F, Benke D, Wang Y, Scheurer L, Luddens H, Hamilton BJ, Carter DB, Mohler H, Benson JA (1996) Pharmacological modulation of the diazepam-insensitive recombinant gamma-aminobutyric acidA receptors alpha 4 beta 2 gamma 2 and alpha 6 beta 2 gamma 2. Mol Pharm 50:1253–1261Google Scholar
  91. 91.
    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 186:443–465PubMedGoogle Scholar
  92. 92.
    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
  93. 93.
    Krishek BJ, Moss SJ, Smart TG (1998) Interaction of H+ and Zn2+ on recombinant and native rat neuronal GABAA receptors. J Physiol 507:639–652PubMedGoogle Scholar
  94. 94.
    Krishtal OA, Osipchuk Yu V, Vrublevsky SV (1988) Properties of glycine-activated conductances in rat brain neurones. Neurosci Lett 84:271–276PubMedGoogle Scholar
  95. 95.
    Laine J, Axelrad H (1996) Morphology of the Golgi-impregnated Lugaro cell in the rat cerebellar cortex: a reappraisal with a description of its axon. J Comp Neurol 375:618–640PubMedGoogle Scholar
  96. 96.
    Laine J, Axelrad H (1998) Lugaro cells target basket and stellate cells in the cerebellar cortex. Neurorep 9:2399–2403Google Scholar
  97. 97.
    Laube B (2002) Potentiation of inhibitory glycinergic neurotransmission by Zn2+: a synergistic interplay between presynaptic P2X2 and postsynaptic glycinergic receptors. Eur J Neurosci 16:1025–1036PubMedGoogle Scholar
  98. 98.
    Laube B, Kuhse J, Rundstrom N, Kirsch J, Schmieden V, Betz H (1995) Modulation by zinc ions of native rat and recombinant human inhibitory glycinergic receptors. J Physiol 483:613–619PubMedGoogle Scholar
  99. 99.
    Laube B, Kuhse J, Betz H (2000) Kinetic and mutational analysis of Zn2+ modulation of recombinant human inhibitory glycinergic receptors. J Physiol 522 Pt 2:215–230Google Scholar
  100. 100.
    Legendre P (1998) A reluctant gating mode of glycinergic receptor channels determines the time course of inhibitory miniature synaptic events in zebrafish hindbrain neurons. J Neurosci 18:2856–2870PubMedGoogle Scholar
  101. 101.
    Legendre P (2001) The glycinergic inhibitory synapse. Cell Mol Life Sci 58:760–793PubMedGoogle Scholar
  102. 102.
    Legendre P, Muller E, Badiu CI, Meier J, Vannier C, Triller A (2002) Desensitization of homomeric alpha1 glycinergic receptor increases with receptor density. Mol Pharmacol 62:817–827PubMedGoogle Scholar
  103. 103.
    Lim R, Alvarez FJ, Walmsley B (2000) GABA mediates presynaptic inhibition at glycinergic synapses in a rat auditory brainstem nucleus. J Physiol 525 Pt 2:447–459Google Scholar
  104. 104.
    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
  105. 105.
    Lu T, Rubio ME, Trussell LO (2008) Glycinergic transmission shaped by the co-release of GABA in a mammalian auditory synapse. Neuron In pressGoogle Scholar
  106. 106.
    Malosio ML, Marqueze-Pouey B, Kuhse J, Betz H (1991) Widespread expression of glycinergic receptor subunit mRNAs in the adult and developing rat brain. EMBO 10:2401–2409Google Scholar
  107. 107.
    Mangin JM, Guyon A, Eugene D, Paupardin-Tritsch D, Legendre P (2002) Functional glycinergic receptor maturation in the absence of glycinergic input in dopaminergic neurones of the rat substantia nigra. J Physio 542:685–697Google Scholar
  108. 108.
    Martin G, Siggins GR (2002) Electrophysiological evidence for expression of glycinergic receptors in freshly isolated neurons from nucleus accumbens. J Pharmacol Exp Ther 302:1135–1145PubMedGoogle Scholar
  109. 109.
    McCool BA, Botting SK (2000) Characterization of strychnine-sensitive glycinergic receptors in acutely isolated adult rat basolateral amygdala neurons. Brain Res 859:341–351PubMedGoogle Scholar
  110. 110.
    McIntire SL, Reimer RJ, Schuske K, Edwards RH, Jorgensen EM (1997) Identification and characterization of the vesicular GABA transporter. Nature 389:870–876PubMedGoogle Scholar
  111. 111.
    Meier J (2003) The enigma of transmitter-selective receptor accumulation at developing inhibitory synapses. Cell Tiss Res 311:271–276Google Scholar
  112. 112.
    Meier J, Grantyn R (2004) A gephyrin-related mechanism restraining glycinergic receptor anchoring at GABAergic synapses. J Neurosci 24:1398–1405PubMedGoogle Scholar
  113. 113.
    Meier J, De Chaldee M, Triller A, Vannier C (2000) Functional heterogeneity of gephyrins. Mol Cell Neurosci 16:566–577PubMedGoogle Scholar
  114. 114.
    Miller PS, Beato M, Harvey RJ, Smart TG (2005) Molecular determinants of glycinergic receptor alphabeta subunit sensitivities to Zn2+-mediated inhibition. J Physiol 566:657–670PubMedGoogle Scholar
  115. 115.
    Miller PS, Da Silva HM, Smart TG (2005) Molecular basis for zinc potentiation at strychnine-sensitive glycinergic receptors. J Biol Chem 280:37877–37884PubMedGoogle Scholar
  116. 116.
    Mitchell SJ, Silver RA (2003) Shunting inhibition modulates neuronal gain during synaptic excitation. Neuron 38:433–445PubMedGoogle Scholar
  117. 117.
    Mitchell EA, Gentet LJ, Dempster J, Belelli D (2007) GABAA and glycinergic receptor-mediated transmission in rat lamina II neurones: relevance to the analgesic actions of neuroactive steroids. J Physiol 583:1021–1040PubMedGoogle Scholar
  118. 118.
    Mori M, Gahwiler BH, Gerber U (2002) Beta-alanine and taurine as endogenous agonists at glycinergic receptors in rat hippocampus in vitro. J Physiol 539:191–200PubMedGoogle Scholar
  119. 119.
    Moss SJ, Smart TG (2001) Constructing inhibitory synapses. Nature Rev 2:240–250Google Scholar
  120. 120.
    Mozrzymas JW (2004) Dynamism of GABA(A) receptor activation shapes the “personality” of inhibitory synapses. Neuropharmacol 47:945–960Google Scholar
  121. 121.
    Mugnaini E, Floris A (1994) The unipolar brush cell: a neglected neuron of the mammalian cerebellar cortex. J comparative neurology 339:174–180Google Scholar
  122. 122.
    Mukhtarov M, Ragozzino D, Bregestovski P (2005) Dual Ca2+ modulation of glycinergic synaptic currents in rodent hypoglossal motoneurones. J Physiol 569:817–831PubMedGoogle Scholar
  123. 123.
    Muller E, Triller A, Legendre P (2004) Glycinergic receptors and GABAergic receptor alpha 1 and gamma 2 subunits during the development of mouse hypoglossal nucleus. Eur J Neurosci 20:3286–3300PubMedGoogle Scholar
  124. 124.
    Muller E, Le Corronc H, Triller A, Legendre P (2006) Developmental dissociation of presynaptic inhibitory neurotransmitter and postsynaptic receptor clustering in the hypoglossal nucleus. Mol Cell Neurosci 32:254–273PubMedGoogle Scholar
  125. 125.
    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. Nature Neurosci 7:17–23PubMedGoogle Scholar
  126. 126.
    Nevin ST, Cromer BA, Haddrill JL, Morton CJ, Parker MW, Lynch JW (2003) Insights into the structural basis for zinc inhibition of the glycinergic receptor. J Biol Chem 278:28985–28992PubMedGoogle Scholar
  127. 127.
    Nunzi MG, Shigemoto R, Mugnaini E (2002) Differential expression of calretinin and metabotropic glutamate receptor mGluR1alpha defines subsets of unipolar brush cells in mouse cerebellum. J Comp Neurol 451:189–199PubMedGoogle Scholar
  128. 128.
    Nusser Z, Naylor D, Mody I (2001) Synapse-specific contribution of the variation of transmitter concentration to the decay of inhibitory postsynaptic currents. Biophys J 80:1251–1261PubMedGoogle Scholar
  129. 129.
    O'Brien JA, Berger AJ (1999) Co-transmission of GABA and glycine to brain stem motoneurons. J Neurophysiol 82:1638–1641PubMedGoogle Scholar
  130. 130.
    O'Brien JA, Berger AJ (2001) The nonuniform distribution of the GABA(A) receptor alpha 1 subunit influences inhibitory synaptic transmission to motoneurons within a motor nucleus. J Neurosci 21:8482–8494PubMedGoogle Scholar
  131. 131.
    Oertel D (1991) The role of intrinsic neuronal properties in the encoding of auditory information in the cochlear nuclei. Curr Opin Neurobiol 1:221–228PubMedGoogle Scholar
  132. 132.
    Oertel D, Young ED (2004) What’s a cerebellar circuit doing in the auditory system? TINS 27:104–110PubMedGoogle Scholar
  133. 133.
    Ohno K, Koroll M, El Far O, Scholze P, Gomeza J, Betz H (2004) The neuronal glycine transporter 2 interacts with the PDZ domain protein syntenin-1. Mol Cell Neurosci 26:518–529PubMedGoogle Scholar
  134. 134.
    Ottersen OP, Davanger S, Storm-Mathisen J (1987) Glycine-like immunoreactivity in the cerebellum of rat and Senegalese baboon, Papio papio: a comparison with the distribution of GABA-like immunoreactivity and with [3H]glycine and [3H]GABA uptake. Exp Brain Res 66:211–221PubMedGoogle Scholar
  135. 135.
    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
  136. 136.
    Pedroarena CM, Kamphausen S (2007) Glycinergic synaptic currents in the deep cerebellar nuclei. NeuropharmacolGoogle Scholar
  137. 137.
    Poisbeau P, Patte-Mensah C, Keller AF, Barrot M, Breton JD, Luis-Delgado OE, Freund-Mercier MJ, Mensah-Nyagan AG, Schlichter R (2005) Inflammatory pain upregulates spinal inhibition via endogenous neurosteroid production. J Neurosci 25:11768–11776PubMedGoogle Scholar
  138. 138.
    Poyatos I, Ponce J, Aragon C, Gimenez C, Zafra F (1997) The glycine transporter GLYT2 is a reliable marker for glycine-immunoreactive neurons. Brain Res Mol Brain Res 49:63–70PubMedGoogle Scholar
  139. 139.
    Prior P, Schmitt B, Grenningloh G, Pribilla I, Multhaup G, Beyreuther K, Maulet Y, Werner P, Langosch D, Kirsch J, et al. (1992) Primary structure and alternative splice variants of gephyrin, a putative glycinergic receptor-tubulin linker protein. Neuron 8:1161–1170PubMedGoogle Scholar
  140. 140.
    Racca C, Gardiol A, Triller A (1998) Cell-specific dendritic localization of glycinergic receptor alpha subunit messenger RNAs. Neurosci 84:997–1012Google Scholar
  141. 141.
    Rampon C, Luppi PH, Fort P, Peyron C, Jouvet M (1996) Distribution of glycine-immunoreactive cell bodies and fibers in the rat brain. Neurosci 75:737–755Google Scholar
  142. 142.
    Ransom BR, Bullock PN, Nelson PG (1977) Mouse spinal cord in cell culture. III. Neuronal chemosensitivity and its relationship to synaptic activity. J Neurophysiol 40:1163–1177Google Scholar
  143. 143.
    Rigo JM, Badiu CI, Legendre P (2003) Heterogeneity of postsynaptic receptor occupancy fluctuations among glycinergic inhibitory synapses in the zebrafish hindbrain. J Physiol 553:819–832PubMedGoogle Scholar
  144. 144.
    Rossi DJ, Hamann M (1998) Spillover-mediated transmission at inhibitory synapses promoted by high affinity alpha6 subunit GABA(A) receptors and glomerular geometry. Neuron 20:783–795PubMedGoogle Scholar
  145. 145.
    Rozzo A, Armellin M, Franzot J, Chiaruttini C, Nistri A, Tongiorgi E (2002) Expression and dendritic mRNA localization of GABAC receptor rho1 and rho2 subunits in developing rat brain and spinal cord. Eur J Neurosci 15:1747–1758PubMedGoogle Scholar
  146. 146.
    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
  147. 147.
    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
  148. 148.
    Sassoe-Pognetto M, Fritschy JM (2000) Mini-review: gephyrin, a major postsynaptic protein of GABAergic synapses. Eur J Neurosci 12:2205–2210PubMedGoogle Scholar
  149. 149.
    Sato K, Zhang JH, Saika T, Sato M, Tada K, Tohyama M (1991) Localization of glycinergic receptor alpha 1 subunit mRNA-containing neurons in the rat brain: an analysis using in situ hybridization histochemistry. Neurosci 43:381–395Google Scholar
  150. 150.
    Sato K, Kiyama H, Tohyama M (1992) Regional distribution of cells expressing glycinergic receptor alpha 2 subunit mRNA in the rat brain. Brain Res 590:95–108PubMedGoogle Scholar
  151. 151.
    Saxena NC, Macdonald RL (1994) Assembly of GABAA receptor subunits: role of the delta subunit. J Neurosci 14:7077–7086PubMedGoogle Scholar
  152. 152.
    Saxena NC, Macdonald RL (1996) Properties of putative cerebellar gamma-aminobutyric acid A receptor isoforms. Mol Pharmacol 49:567–579PubMedGoogle Scholar
  153. 153.
    Schmieden V, Kuhse J, Betz H (1993) Mutation of glycinergic receptor subunit creates beta-alanine receptor responsive to GABA. Science 262:256–258PubMedGoogle Scholar
  154. 154.
    Sergeeva OA (1998) Comparison of glycine- and GABA-evoked currents in two types of neurons isolated from the rat striatum. Neurosci Lett 243:9–12PubMedGoogle Scholar
  155. 155.
    Sergeeva OA, Haas HL (2001) Expression and function of glycinergic receptors in striatal cholinergic interneurons from rat and mouse. Neurosci 104:1043–1055Google Scholar
  156. 156.
    Simat M, Parpan F, Fritschy JM (2007) Heterogeneity of glycinergic and gabaergic interneurons in the granule cell layer of mouse cerebellum. J Comp Neurol 500:71–83PubMedGoogle Scholar
  157. 157.
    Singer JH, Talley EM, Bayliss DA, Berger AJ (1998) Development of glycinergic synaptic transmission to rat brain stem motoneurons. J Neurophysiol 80:2608–2620PubMedGoogle Scholar
  158. 158.
    Smith AJ, Owens S, Forsythe ID (2000) Characterization of inhibitory and excitatory postsynaptic currents of the rat medial superior olive. J Physiol 529:681–698PubMedGoogle Scholar
  159. 159.
    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. Neurosci 77:543–551Google Scholar
  160. 160.
    Suwa H, Saint-Amant L, Triller A, Drapeau P, Legendre P (2001) High-affinity zinc potentiation of inhibitory postsynaptic glycinergic currents in the zebrafish hindbrain. J Neurophysiol 85:912–925PubMedGoogle Scholar
  161. 161.
    Takahashi T (2005) Postsynaptic receptor mechanisms underlying developmental speeding of synaptic transmission. Neurosci Res 53:229–240PubMedGoogle Scholar
  162. 162.
    Takahashi T, Momiyama A, Hirai K, Hishinuma F, Akagi H (1992) Functional correlation of fetal and adult forms of glycinergic receptors with developmental changes in inhibitory synaptic receptor channels. Neuron 9:1155–1161PubMedGoogle Scholar
  163. 163.
    Takahashi Y, Shirasaki T, Yamanaka H, Ishibashi H, Akaike N (1994) Physiological roles of glycine and gamma-aminobutyric acid in dissociated neurons of rat visual cortex. Brain Res 640:229–235PubMedGoogle Scholar
  164. 164.
    Taleb O, Betz H (1994) Expression of the human glycinergic receptor alpha 1 subunit in Xenopus oocytes: apparent affinities of agonists increase at high receptor density. EMBO 13:1318–1324Google Scholar
  165. 165.
    Thio LL, Shanmugam A, Isenberg K, Yamada K (2003) Benzodiazepines block alpha2-containing inhibitory glycinergic receptors in embryonic mouse hippocampal neurons. J Neurophysiol 90:89–99PubMedGoogle Scholar
  166. 166.
    Todd AJ (1990) An electron microscope study of glycine-like immunoreactivity in laminae I-III of the spinal dorsal horn of the rat. Neurosci 39:387–394Google Scholar
  167. 167.
    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
  168. 168.
    Todd AJ, Watt C, Spike RC, Sieghart W (1996) Colocalization of GABA, glycine, and their receptors at synapses in the rat spinal cord. J Neurosci 16:974–982PubMedGoogle Scholar
  169. 169.
    Tretter V, Jacob TC, Mukherjee J, Fritschy JM, Pangalos MN, Moss SJ (2008) The clustering of GABA(A) receptor subtypes at inhibitory synapses is facilitated via the direct binding of receptor alpha2 subunits to gephyrin. J Neurosci 28:1356–1365PubMedGoogle Scholar
  170. 170.
    Triller A, Choquet D (2003) Synaptic structure and diffusion dynamics of synaptic receptors. Biology of the cell / under the auspices of the European Cell Biol Organ 95:465–476Google Scholar
  171. 171.
    Triller A, Cluzeaud F, Korn H (1987) gamma-Aminobutyric acid-containing terminals can be apposed to glycinergic receptors at central synapses. J Cell Biol 104:947–956PubMedGoogle Scholar
  172. 172.
    Trombley PQ, Hill BJ, Horning MS (1999) Interactions between GABA and glycine at inhibitory amino acid receptors on rat olfactory bulb neurons. J Neurophysiol 82:3417–3422PubMedGoogle Scholar
  173. 173.
    Twyman RE, Macdonald RL (1991) Kinetic properties of the glycinergic receptor main- and sub-conductance states of mouse spinal cord neurones in culture. J Physiol 435:303–331PubMedGoogle Scholar
  174. 174.
    van den Pol AN, Gorcs T (1988) Glycine and glycinergic receptor immunoreactivity in brain and spinal cord. J Neurosci 8:472–492PubMedGoogle Scholar
  175. 175.
    Waldvogel HJ, Baer K, Allen KL, Rees MI, Faull RL (2007) Glycinergic receptors in the striatum, globus pallidus, and substantia nigra of the human brain: an immunohistochemical study. J Comp Neurol 502:1012–1029PubMedGoogle Scholar
  176. 176.
    Wang Z, Danscher G, Kim YK, Dahlstrom A, Mook Jo S (2002) Inhibitory zinc-enriched terminals in the mouse cerebellum: double-immunohistochemistry for zinc transporter 3 and glutamate decarboxylase. Neurosci Lett 321:37–40PubMedGoogle Scholar
  177. 177.
    Wang Z, Danscher G, Mook Jo S, Shi Y, Daa Schroder H (2001) Retrograde tracing of zinc-enriched (ZEN) neuronal somata in rat spinal cord. Brain Res 900:80–87PubMedGoogle Scholar
  178. 178.
    Wang Z, Li JY, Dahlstrom A, Danscher G (2001) Zinc-enriched GABAergic terminals in mouse spinal cord. Brain Res 921:165–172PubMedGoogle Scholar
  179. 179.
    Wang ZY, Stoltenberg M, Huang L, Danscher G, Dahlstrom A, Shi Y, Li JY (2005) Abundant expression of zinc transporters in Bergman glia of mouse cerebellum. Brain Res Bull 64:441–448PubMedGoogle Scholar
  180. 180.
    Wei W, Zhang N, Peng Z, Houser CR, Mody I (2003) Perisynaptic localization of delta subunit-containing GABA(A) receptors and their activation by GABA spillover in the mouse dentate gyrus. J Neurosci 23:10650–10661PubMedGoogle Scholar
  181. 181.
    Wenthold RJ, Huie D, Altschuler RA, Reeks KA (1987) Glycine immunoreactivity localized in the cochlear nucleus and superior olivary complex. Neurosci 22:897–912Google Scholar
  182. 182.
    Werman R, Davidoff RA, Aprison MH (1968) Inhibitory of glycine on spinal neurons in the cat. J Neurophysiol 31:81–95PubMedGoogle Scholar
  183. 183.
    Wilkin GP, Csillag A, Balazs R, Kingsbury AE, Wilson JE, Johnson AL (1981) Localization of high affinity [3H]glycine transport sites in the cerebellar cortex. Brain Res 216:11–33PubMedGoogle Scholar
  184. 184.
    Zafra F, Aragon C, Olivares L, Danbolt NC, Gimenez C, Storm-Mathisen J (1995) Glycine transporters are differentially expressed among CNS cells. J Neurosci 15:3952–3969PubMedGoogle Scholar
  185. 185.
    Zeilhofer HU, Studler B, Arabadzisz D, Schweizer C, Ahmadi S, Layh B, Bosl MR, Fritschy JM (2005) Glycinergic neurons expressing enhanced green fluorescent protein in bacterial artificial chromosome transgenic mice. J Comp Neurol 482:123–141PubMedGoogle Scholar
  186. 186.
    Zhang D, Pan ZH, Awobuluyi M, Lipton SA (2001) Structure and function of GABA(C) receptors a comparison of native versus recombinant receptors. TIPS 22:121–132PubMedGoogle Scholar
  187. 187.
    Zhang LH, Gong N, Fei D, Xu L, Xu TL (2008) Glycine Uptake Regulates Hippocampal Network Activity via Glycinergic receptor-Mediated Tonic Inhibition. Neuropsychopharmacol 33:701–711Google Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Laboratoire de neurobiologieCNRS UMR8544, Ecole normale supérieure75005 Paris, France

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