Skip to main content

Presynaptic Ionotropic GABA Receptors

A homeostatic feedback mechanism at axon terminals of inhibitory interneurons

  • Chapter
  • 670 Accesses

4. Conclusions

Presynaptic autoreceptors modulate the release of GABA from terminals of inhibitory interneurons. We have shown that in rodent hippocampal CA3 this feedback involves the activation of ionotropic GABAAR which suppress further release in acutely prepared tissue. Under conditions of different EC1, the same feedback might be positively coupled to release, giving rise to bursts of IPSCs after an initial (large) event. Our further experimental and theoretical studies show that presynaptic ionotropic GABAAR are specifically important during one mechanism of inhibitory synaptic plasticity, namely changes in GABA metabolism. Besides alterations of the amount of released GABA this homeostatic mechanism induces changes in the frequency of vesicle release which are likely to be mediated by presynaptic ionotropic GABAAR. This new feedback mechanism will be important to understand the dynamics of inibitory synaptic signaling and the ratio between tonic and phasic GABAergic inhibition.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

6. References

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Axmacher N, Winterer J, Stanton PK, Draguhn A, Muller W (2004c) Two-photon i maging of spontaneous vesicular release in acute brain slices and its modulation by presynaptic GABAA receptors. Neuroimage 22:1014–1021.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • 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 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • 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 535:473–82.

    Article  PubMed  CAS  Google Scholar 

  • Esclapez M, Houser CR (1999) Up-regulation of GAD65 and GAD67 in remaining hippocampal GABA neurons in a model of temporal lobe epilepsy. J Comp Neurol 412:488–505.

    Article  PubMed  CAS  Google Scholar 

  • Feldblum S, Ackermann RF, Tobin AJ (1990) Long-term increase of glutamate decarboxylase mRNA in a rat model of temporal lobe epilepsy. Neuron 5:361–371.

    Article  PubMed  CAS  Google Scholar 

  • Frerking M, Borges S, Wilson M (1995) Variation in GABA mini amplitude is the consequence of variation in transmitter concentration. Neuron 15:885–895.

    Article  PubMed  CAS  Google Scholar 

  • Frerking M, Wilson M (1996) Saturation of postsynaptic receptors at central synapses? Curr Opin Neurobiol 6:395–403.

    Article  PubMed  CAS  Google Scholar 

  • Garraghty PE, LaChica AE, Kaas JH (1991) Injury-induced reorganization of somatosensory cortex is accompanied by reductions in GABA staining. Somatosens Mot Res 8:347–354.

    Article  PubMed  CAS  Google Scholar 

  • Gierdalski M, Jablonska B, Smith A, Skangiel-Kramska J, Kossut M (1999) Deafferentation induced changes in GAD67 and GluR2 mRNA expression in mouse somatosensory cortex. Brain Res Mol Brain Res 71:111–119.

    Article  PubMed  CAS  Google Scholar 

  • Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391:85–100.

    Article  PubMed  CAS  Google Scholar 

  • Hendry S, Carder RK (1992) Organization and plasticity of GABA neurons and receptors in monkey visual cortex. Prog Brain Res 90:477–502.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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 

  • 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 

  • MacDermott AB, Role LW, Siegelbaum SA. (1999) Presynaptic ionotropic receptors and the control of transmitter release. Annu Rev Neurosci 22:443–85.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Nusser Z, Cull-Candy S, Farrant M (1997) Differences in synaptic GABA(A) receptor number underlie variation in GABA mini amplitude. Neuron 19:697–709.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Stanton P, Heinemann U, Muller W (2001) FM1-43 imaging reveals cGMP-dependent long-term depression of presynaptic transmitter release. J Neurosci 21:167–173.

    Google Scholar 

  • Stanton PK, Winterer J, Bailey CP, Kyrozis A, Raginov I, Laube G, Veh RW, Nguyen CQ, Muller W (2003) Long-term depression of presynaptic release from the readily releasable vesicle pool induced by NMDA receptor-dependent retrograde nitric oxide. J Neurosci 23:5936–44.

    PubMed  CAS  Google Scholar 

  • Stasheff SF, Mott DD, Wilson WA (1993) 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 

  • Stell BM, Mody I (2002) Receptors with different affinities mediate phasic and tonic GABA(A) conductances in hippocampal neurons. J Neurosci 22:223–227.

    Google Scholar 

  • Stoppini L, Buchs PA, Muller D (1991) A simple method for organotypic cultures of nervous tissue. J Neurosci Methods 37:173–182.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • 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 

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

    Article  PubMed  CAS  Google Scholar 

  • Turrigiano GG (1999) Homeostatic plasticity in neuronal networks: the more things change, the more they stay the same. Trends Neurosci 22:221–227.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • 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 

  • Wu Y, Wang W, Richerson GB (2003) Vigabatrin induces tonic inhibition via GABA transporter reversal without increasing vesicular GABA release. J Neurophysiol 89:2021–2034.

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto N, Kurotani T, Toyama K (1989) Neural connections between the lateral geniculate nucleus and visual cortex in vitro. Science 245:192–194.

    PubMed  CAS  Google Scholar 

  • Yamamoto N, Yamada K, Kurotani T, Toyama K (1992) Laminar specificity of extrinsic cortical connections studied in coculture preparations. Neuron 9:217–228.

    Article  PubMed  CAS  Google Scholar 

  • Yee JM, Agulian S, Kocsis JD (1998) Vigabatrin enhances promoted release of GABA in neonatal rat optic nerve. Epilepsy Res 29:195–200.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer Science+Business Media, Inc.

About this chapter

Cite this chapter

Axmacher, N., Hartmann, K., Draguhn, A. (2005). Presynaptic Ionotropic GABA Receptors. In: Stanton, P.K., Bramham, C., Scharfman, H.E. (eds) Synaptic Plasticity and Transsynaptic Signaling. Springer, Boston, MA. https://doi.org/10.1007/0-387-25443-9_6

Download citation

Publish with us

Policies and ethics