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Presynaptic Ionotropic GABA Receptors

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Inhibitory Regulation of Excitatory Neurotransmission

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 44))

Abstract

Following the classical work on presynaptic inhibition in the spinal cord, recent work has revealed an astonishing abundance and diversity of presynaptic ionotropic GABA receptors. While modern techniques allow for detailed studies at the cellular and molecular level in almost all regions of the CNS, our understanding of the function of such receptors is still far from complete. One major shortcoming is the lack of knowledge regarding chloride concentration inside axons or axon terminals. Therefore, the voltage change upon activation of presynaptic GABA receptors is difficult to predict. Moreover, even if the presynaptic potential transient was known, it turns out difficult to predict the effects on presynaptic function, which may be differentially influenced by various mechanisms, including activation or inactivation of voltage-gated ion channels and shunt effects. This review summarizes several key examples of presynaptic ionotropic GABA receptors and outlines the possible mechanisms that have to be kept in mind when unravelling this potentially important mechanism of synaptic signalling and plasticity.

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References

  1. Alvarez-Leefmans FJ, Gamino SM, Giraldez F, Nogueron I (1988) Intracellular chloride regulation in amphibian dorsal root ganglion neurones studied with ion-selective microelectrodes. J Physiol 406:225–246

    PubMed  CAS  Google Scholar 

  2. Axmacher N, Draguhn A (2004) Inhibition of GABA release by presynaptic ionotropic GABA receptors in hippocampal CA3. NeuroReport 15:329–334

    Article  PubMed  CAS  Google Scholar 

  3. Axmacher N, Winterer J, Stanton PK, Draguhn A, Müller W (2004a) Two-photon imaging of spontaneous vesicular release in acute brain slices and its modulation by presynaptic GABA(A) receptors. Neuroimage 22:1014–1021

    Article  PubMed  Google Scholar 

  4. Axmacher N, Stemmler M, Engel D, Draguhn A, Ritz R (2004b) Transmitter metabolism as a mechanism of synaptic plasticity: a modelling study. J Neurophysiol 91:25–39

    Article  PubMed  CAS  Google Scholar 

  5. Barron DH, Mathews BHC (1938) Dorsal root reflexes. J Physiol 94:26P–27P

    Google Scholar 

  6. Belenky MA, Sagiv N, Fritschy JM, Yarom Y (2003) Presynaptic and postsynaptic GABA-A receptors in rat suprachiasmatic nucleus. Neuroscience 118:909–923

    Article  PubMed  CAS  Google Scholar 

  7. Betz WJ, Bewick GS (1992) Optical analysis of synaptic vesicle recycling at the frog neuromuscular junction. Science 255:200–203

    Article  PubMed  CAS  Google Scholar 

  8. Bormann J, Feigenspan A (1995) GABAC receptors. Trends Neurosci 18:515–519

    Article  PubMed  CAS  Google Scholar 

  9. Cattaert D, Libersat F, El Manira AA (2001) Presynaptic inhibition and antidromic spikes in primary afferents of the crayfish: a computational and experimental analysis. J Neurosci 21:1007–1021

    PubMed  CAS  Google Scholar 

  10. Chavas J, Marty A (2003) Coexistence of excitatory and inhibitory GABA synapses in the cerebellar interneuron network. J Neurosci 23:2019–1031

    PubMed  CAS  Google Scholar 

  11. Chavas J, Forero ME, Collin T, Llano I, Marty A (2004) Osmotic tension as a possible link between GABA(A) receptor activation and intracellular calcium elevation. Neuron 44:701–713

    Article  PubMed  CAS  Google Scholar 

  12. Csicsvari J, Hirase H, Czurkó A, Mamiya A Buzsáki G (1999) Oscillatory coupling of hippocampal pyramidal cells and interneurons in the behaving rat. J Neurosci 19:274–287

    PubMed  CAS  Google Scholar 

  13. Davies CH, Davies SN, Collingridge GL (1990) Paired-pulse depression of monosynaptic GABA-mediated inhibitory postsynaptic responses in rat hippocampus. J Physiol 424:513–531

    PubMed  CAS  Google Scholar 

  14. Dittman JS, Regehr WG (1997) Mechanism and kinetics of heterosynaptic depression at a cerebellar synapse. J Neurosci 17:9048–9059

    PubMed  CAS  Google Scholar 

  15. Duenas SH, Rudomin P (1988) Excitability changes of ankle extensor group Ia and Ib fibers during fictive locomotion in the cat. Exp Brain Res 70:15–25

    PubMed  CAS  Google Scholar 

  16. Ebihara S, Shirato K, Harata N, Akaike N (1995) Gramicidin-perforated patch recording: GABA response in mammalian neurones with intact intracellular chloride. J Physiol 484:77–86

    PubMed  CAS  Google Scholar 

  17. Eccles JC (1964) Presynaptic inhibition in the spinal cord. Progr Brain Res 12:65–91

    Article  CAS  Google Scholar 

  18. Eccles JC, Schmidt R, Willis WD (1963) Pharmacological studies on presynaptic inhibition. J Physiol 168:500–530

    PubMed  CAS  Google Scholar 

  19. Eccles JC, Schmidt RF, Willis WD (1962) Presynaptic inhibition of the spinal monosynaptic reflex pathway. J Physiol 161:282–297

    PubMed  CAS  Google Scholar 

  20. Engel D, Pahner I, Schulze K, Frahm C, Jarry H, Ahnert-Hilger G Draguhn A (2001) Plasticity of rat central inhibitory synapses through GABA metabolism. J Physiol 535:473–482

    Article  PubMed  CAS  Google Scholar 

  21. Eguibar JR, Quevedo J, Rudomin P (1997) Selective cortical and segmental control of primary afferent depolarization of single muscle afferents in the cat spinal cord. Exp Brain Res 113:411–430

    Article  PubMed  CAS  Google Scholar 

  22. Eguibar JR, Quevedo J, Jimenez I, Rudomin P (1994) Selective cortical control of information flow through different intraspinal collaterals of the same muscle afferent fiber. Brain Res 643:328–333

    Article  PubMed  CAS  Google Scholar 

  23. Farrant M, Nusser Z (2005) Variations on an inhibitory theme: phasic and tonic activation of GABA(A)receptors. Nat Rev Neurosci 6:215–229

    Article  PubMed  CAS  Google Scholar 

  24. Frank K, Fuortes MGF (1957) Presynaptic and postsynaptic inhibition of monosynaptic reflexes. Fed Proc 16:39–40

    Google Scholar 

  25. Gray EG (1962) A morphological basis for pre-synaptic inhibition? Nature 193:82–83

    Article  PubMed  CAS  Google Scholar 

  26. Gutierrez R (2005) The dual glutamatergic–GABAergic phenotype of hippocampal granule cells. Trends Neurosci 28:297–303

    Article  PubMed  CAS  Google Scholar 

  27. Hochner B, Parnas H, Parnas I (1989) Membrane depolarization evokes neurotransmitter release in the absence of calcium entry. Nature 342:433–435

    Article  PubMed  CAS  Google Scholar 

  28. Hull C, von Gersdorff H (2004) Fast endocytosis is inhibited by GABA-mediated chloride influx at a presynaptic terminal. Neuron 44:469–482

    Article  PubMed  CAS  Google Scholar 

  29. Isaacson JS, Solis JM, Nicoll RA (1993) Local and diffuse synaptic actions of GABA in the hippocampus. Neuron 10:165–175

    Article  PubMed  CAS  Google Scholar 

  30. Jang IS, Jeong HJ, Katsurabayashi S, Akaike N (2002) Functional roles of presynaptic GABAA receptors on glycinergic nerve terminals in the rat spinal cord. J Physiol 541:423–434

    Article  PubMed  CAS  Google Scholar 

  31. Kamermans M, Werblin F (1992) GABA-mediated positive autofeedback loop controls horizontal cell kinetics in tiger salamander retina. J Neurosci 12:2451–2463

    PubMed  CAS  Google Scholar 

  32. Kaupmann K, Huggel K, Heid J, Flor PJ, Bischoff S, Mickel SJ, McMaster G, Angst C, Bittiger H, Froestl W, Bettler B (1997) Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors. Nature 386:239–246

    Article  PubMed  CAS  Google Scholar 

  33. Klausberger T, Magill PJ, Marton LF, Roberts JD, Cobden PM, Buzsáki G, Somogyi P (2003) Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo. Nature 421:844–848

    Article  PubMed  CAS  Google Scholar 

  34. Kondo H, Toyoda J (1983) GABA and glycine effects on the bipolar cells of the carp retina. Vision Res 23:1259–1264

    Article  PubMed  CAS  Google Scholar 

  35. Kulik A, Vida I, Lujan R, Haas CA, Lopez-Bendito G, Shigemoto R, Frotscher M (2003) Subcellular localization of metabotropic GABA(B) receptor subunits GABA(B1a/b) and GABA(B2) in the rat hippocampus. J Neurosci 23:11026–11035

    PubMed  CAS  Google Scholar 

  36. Kremer E, Lev-Tov A (1998) GABA-receptor-independent dorsal root afferents depolarization in the neonatal rat spinal cord. J Neurophysiol 79:2581–2592

    PubMed  CAS  Google Scholar 

  37. Kullmann DM, Ruiz A, Rusakov DM, Scott R, Semyanov A, Walker MC (2005) Presynaptic, extrasynaptic and axonal GABAA receptors in the CNS: where and why? Prog Biophys Mol Biol 87:33–46

    Article  PubMed  CAS  Google Scholar 

  38. Kuner T, Augustine GJ (2000) A genetically encoded ratiometric indicator for chloride: capturing chloride transients in cultured hippocampal neurons. Neuron 27:447–459

    Article  PubMed  CAS  Google Scholar 

  39. Kuner R, Kohr G, Grunewald S, Eisenhardt G, Bach A, Kornau HC (1999) Role of heteromer formation in GABAB receptor function. Science 283:74–77

    Article  PubMed  CAS  Google Scholar 

  40. MacDermott AB, Role LW, Siegelbaum SA (1999) Presynaptic ionotropic receptors and the control of transmitter release. Ann Rev Neurosci 22:443–485

    Article  PubMed  CAS  Google Scholar 

  41. Maxwell DJ, Kerr R, Jankowska E, Ridell JS (1997) Synaptic connections of dorsal horn group II spinal interneurons: synapses formed with the interneurons and by their axon collaterals. J Com Neurol 380:51–69

    Article  CAS  Google Scholar 

  42. Misgeld U, Bijak M, Jarolimek W (1995) A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system. Prog Neurobiol 46:423–462

    Article  PubMed  CAS  Google Scholar 

  43. Nicoll RA, Alger BE (1979) Presynaptic inhibition: transmitter and ionic mechanisms. Int Rev Neurobiol 21:217–258

    Article  PubMed  CAS  Google Scholar 

  44. Nusser Z, Sieghart W, Benke D, Fritschy JM, Somogyi P (1996) Differential syaptic localization of two major γ-aminobutyric acid type A receptor α subunits on hippocampal pyramidal cells. Proc Natl Acad Sci USA 93:11939–11944

    Article  PubMed  CAS  Google Scholar 

  45. Overstreet LS, Westbrook GL (2001) Paradoxical reduction of synaptic inhibition by vigabatrin. J Neurophysiol 86:596–603

    PubMed  CAS  Google Scholar 

  46. Parnas I, Rashkovan G, Ravin R, Fischer Y (2000) Novel mechanism for presynaptic inhibition: GABA(A) receptors affect the release machinery. J Neurophysiol 84:1240–1246

    PubMed  CAS  Google Scholar 

  47. Pouzat C, Marty A (1999) Somatic recording of GABAergic autoreceptor current in cerebellar stellate and basket cells. J Neurosci 19:1675–1690

    PubMed  CAS  Google Scholar 

  48. Rudomin P, Schmidt RF (1999) Presynaptic inhibition in the vertebrate spinal cord revisited. Exp Brain Res 129:1–37

    Article  PubMed  CAS  Google Scholar 

  49. Ruiz A, Fabian-Fine R, Scott R, Walker MC, Rusakov DA, Kullmann DM (2003) GABAA receptors at hippocampal mossy fibers. Neuron 39:961–973

    Article  PubMed  CAS  Google Scholar 

  50. Ryan TA, Reuter H, Wendland B, Schweizer FE, Tsien RW, Smith SJ (1993) The kinetics of synaptic vesicle recycling measured at single presynaptic boutons. Neuron 11:713–724

    Article  PubMed  CAS  Google Scholar 

  51. Satzler K, Sohl LF, Bollmann JH, Borst JG, Frotscher M, Sakmann B, Lubke JH (2002) Three-dimensional reconstruction of a calyx of Held and its postsynaptic principal neuron in the medial nucleus of the trapezoid body. J Neurosci 22:10567–10579

    PubMed  CAS  Google Scholar 

  52. Schmitz D, Frerking M, Nicoll RA (2000) Synaptic activation of presynaptic kainite receptors on hippocampal mossy fiber synapses. Neuron 27:327–338

    Article  PubMed  CAS  Google Scholar 

  53. Semyanov A, Walker MC, Kullmann DM, Silver RA (2004) Tonically active GABA A receptors: modulating gain and maintaining the tone. Trends Neurosci 27:262–269

    Article  PubMed  CAS  Google Scholar 

  54. Shields CR, Tran MN, Wong RO, Lukasiewicz PD (2000) Distinct ionotropic GABA receptors mediate presynaptic and postsynaptic inhibition in retinal bipolar cells. J Neurosci 20:2673–2682

    PubMed  CAS  Google Scholar 

  55. Soriano E, Nitsch R, Frotscher M (1990) Axo-axonic chandelier cells in the rat fascia dentata: Golgi-electron microscopy and immunocytochemical studies. J Comp Neurol 293:1–25

    Article  PubMed  CAS  Google Scholar 

  56. Stanton PK, Heinemann U, Müller W (2001) FM1-43 imaging reveals cGMP-dependent long-term depression of presynaptic transmitter release. J Neurosci 21:RC167

    PubMed  CAS  Google Scholar 

  57. Stasheff SF, Hines M, Wilson WA (1993a) Axon terminal hyperexcitability associated with epileptogenesis in vitro. I. Origin of ectopic spikes. J Neurophysiol 70:961–975

    PubMed  CAS  Google Scholar 

  58. Stasheff SF, Mott DD, Wilson WA (1993b) Axon terminal hyperexcitability associated with epileptogenesis in vitro. II. Pharmacological regulation by NMDA and GABAA receptors. J Neurophysiol 70:976–984

    PubMed  CAS  Google Scholar 

  59. Stuart GJ, Redman SJ (1992) The role of GABAA and GABAB receptors in presynaptic inhibition of Ia EPSPs in cat spinal motoneurones. J Physiol 447:675–692

    PubMed  CAS  Google Scholar 

  60. Tachibana M, Kaneko A (1984) Gamma-Aminobutyric acid acts at axon terminals of turtle photoreceptors: difference in sensitivity among cell types. Proc Natl Acad Sci USA 81:7961–7964

    Article  PubMed  CAS  Google Scholar 

  61. Tachibana M, Kaneko A (1987) γ-Aminobutyric acid exerts a local inhibitory action on the axon terminal of bipolar cells: evidence for negative feedback from amacrine cells. Proc Natl Acad Sci USA 84:3501–3505

    Article  PubMed  CAS  Google Scholar 

  62. Todd AJ (1996) GABA and glycine in synptic glomeruli of the rat spinal dorsal horn. Eur J Neurosci 8:2492–2498

    Article  PubMed  CAS  Google Scholar 

  63. Toennies JF (1938) Reflex discharge from the spinal cord over the dorsal roots. J Neurophysiol 1:378–390

    Google Scholar 

  64. Turecek R, Trussell LO (2002) Reciprocal developmental regulation of presynaptic ionotropic receptors. Proc Natl Acad Sci USA 99:13884–13889

    Article  PubMed  CAS  Google Scholar 

  65. Turecek R, Trussell LO (2001) Presynaptic glycine receptors enhance transmitter release at a mammalian central synapse. Nature 411:587–590

    Article  PubMed  CAS  Google Scholar 

  66. Vautrin J, Schaffner AE, Barker JL (1994) Fast presynaptic GABAA receptor-mediated Cl– conductance in cultured rat hippocampal neurones. J Physiol 479:53–63

    PubMed  CAS  Google Scholar 

  67. White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, Barnes AA, Emson P, Foord SM, Marshall FH (1998) Heterodimerization is required for the formation of a functional GABA(B)receptor. Nature 396:679–982

    Article  PubMed  CAS  Google Scholar 

  68. Whittington MA, Traub RD (2003) Interneuron diversity series: inhibitory interneurons and network oscillations in vitro. Trends Neurosci 26:676–682

    Article  PubMed  CAS  Google Scholar 

  69. Williams SR, Stuart GJ (2003) Voltage- and site-dependent control of the somatic impact of dendritic IPSPs. J Neurosci 23:7358–7367

    PubMed  CAS  Google Scholar 

  70. Willis WD Jr (1999) Dorsal root potentials and dorsal root reflexes: a double-edged sword. Exp Brain Res 124:395–421

    Article  PubMed  CAS  Google Scholar 

  71. Zhang SJ, Jackson MB (1993) GABA-activated chloride channels in secretory nerve endings. Science 259:531–534

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institut für Physiologie und Pathophysiologie, Universität Heidelberg, Im Neuenheimer Feld 326, 69120, Heidelberg, Germany

    Andreas Draguhn & Sergej Kolbaev

  2. Klinik für Epileptologie, Universität Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany

    Nikolai Axmacher

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  1. Andreas Draguhn
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  2. Nikolai Axmacher
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  3. Sergej Kolbaev
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Correspondence to Andreas Draguhn .

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Mark G. Darlison

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Draguhn, A., Axmacher, N., Kolbaev, S. (2007). Presynaptic Ionotropic GABA Receptors. In: Darlison, M.G. (eds) Inhibitory Regulation of Excitatory Neurotransmission. Results and Problems in Cell Differentiation, vol 44. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2007_040

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