Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Oct 10;92(21):9515–9519. doi: 10.1073/pnas.92.21.9515

G protein activation kinetics and spillover of gamma-aminobutyric acid may account for differences between inhibitory responses in the hippocampus and thalamus.

A Destexhe 1, T J Sejnowski 1
PMCID: PMC40832  PMID: 7568165

Abstract

We have developed a model of gamma-aminobutyric acid (GABA)ergic synaptic transmission mediated by GABAA and GABAB receptors, including cooperativity in the guanine nucleotide binding protein (G protein) cascade mediating the activation of K+ channels by GABAB receptors. If the binding of several G proteins is needed to activate the K+ channels, then only a prolonged activation of GABAB receptors evoked detectable currents. This could occur if strong stimuli evoked release in adjacent terminals and the spillover resulted in prolonged activation of the receptors, leading to inhibitory responses similar to those observed in hippocampal slices. The same model also reproduced thalamic GABAB responses to high-frequency bursts of stimuli. In this case, prolonged activation of the receptors was due to high-frequency release conditions. This model provides insights into the function of GABAB receptors in normal and epileptic discharges.

Full text

PDF
9515

Images in this article

9516Fig. 2
on p.9516
9518Fig. 4
on p.9518

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Babb T. L., Pretorius J. K., Kupfer W. R., Brown W. J. Distribution of glutamate-decarboxylase-immunoreactive neurons and synapses in the rat and monkey hippocampus: light and electron microscopy. J Comp Neurol. 1988 Dec 1;278(1):121–138. doi: 10.1002/cne.902780108. [DOI] [PubMed] [Google Scholar]
  2. Bal T., von Krosigk M., McCormick D. A. Synaptic and membrane mechanisms underlying synchronized oscillations in the ferret lateral geniculate nucleus in vitro. J Physiol. 1995 Mar 15;483(Pt 3):641–663. doi: 10.1113/jphysiol.1995.sp020612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bartol T. M., Jr, Land B. R., Salpeter E. E., Salpeter M. M. Monte Carlo simulation of miniature endplate current generation in the vertebrate neuromuscular junction. Biophys J. 1991 Jun;59(6):1290–1307. doi: 10.1016/S0006-3495(91)82344-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benardo L. S. Separate activation of fast and slow inhibitory postsynaptic potentials in rat neocortex in vitro. J Physiol. 1994 Apr 15;476(2):203–215. doi: 10.1113/jphysiol.1994.sp020124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Boland L. M., Bean B. P. Modulation of N-type calcium channels in bullfrog sympathetic neurons by luteinizing hormone-releasing hormone: kinetics and voltage dependence. J Neurosci. 1993 Feb;13(2):516–533. doi: 10.1523/JNEUROSCI.13-02-00516.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Busch C., Sakmann B. Synaptic transmission in hippocampal neurons: numerical reconstruction of quantal IPSCs. Cold Spring Harb Symp Quant Biol. 1990;55:69–80. doi: 10.1101/sqb.1990.055.01.009. [DOI] [PubMed] [Google Scholar]
  7. Celentano J. J., Wong R. K. Multiphasic desensitization of the GABAA receptor in outside-out patches. Biophys J. 1994 Apr;66(4):1039–1050. doi: 10.1016/S0006-3495(94)80885-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clark J. A., Amara S. G. Stable expression of a neuronal gamma-aminobutyric acid transporter, GAT-3, in mammalian cells demonstrates unique pharmacological properties and ion dependence. Mol Pharmacol. 1994 Sep;46(3):550–557. [PubMed] [Google Scholar]
  9. Clements J. D., Lester R. A., Tong G., Jahr C. E., Westbrook G. L. The time course of glutamate in the synaptic cleft. Science. 1992 Nov 27;258(5087):1498–1501. doi: 10.1126/science.1359647. [DOI] [PubMed] [Google Scholar]
  10. Davies C. H., Davies S. N., Collingridge G. L. Paired-pulse depression of monosynaptic GABA-mediated inhibitory postsynaptic responses in rat hippocampus. J Physiol. 1990 May;424:513–531. doi: 10.1113/jphysiol.1990.sp018080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Destexhe A., Contreras D., Sejnowski T. J., Steriade M. A model of spindle rhythmicity in the isolated thalamic reticular nucleus. J Neurophysiol. 1994 Aug;72(2):803–818. doi: 10.1152/jn.1994.72.2.803. [DOI] [PubMed] [Google Scholar]
  12. Destexhe A., Mainen Z. F., Sejnowski T. J. Synthesis of models for excitable membranes, synaptic transmission and neuromodulation using a common kinetic formalism. J Comput Neurosci. 1994 Aug;1(3):195–230. doi: 10.1007/BF00961734. [DOI] [PubMed] [Google Scholar]
  13. Dutar P., Nicoll R. A. A physiological role for GABAB receptors in the central nervous system. Nature. 1988 Mar 10;332(6160):156–158. doi: 10.1038/332156a0. [DOI] [PubMed] [Google Scholar]
  14. Dutar P., Nicoll R. A. Pre- and postsynaptic GABAB receptors in the hippocampus have different pharmacological properties. Neuron. 1988 Sep;1(7):585–591. doi: 10.1016/0896-6273(88)90108-0. [DOI] [PubMed] [Google Scholar]
  15. Golard A., Siegelbaum S. A. Kinetic basis for the voltage-dependent inhibition of N-type calcium current by somatostatin and norepinephrine in chick sympathetic neurons. J Neurosci. 1993 Sep;13(9):3884–3894. doi: 10.1523/JNEUROSCI.13-09-03884.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Harris K. M., Landis D. M. Membrane structure at synaptic junctions in area CA1 of the rat hippocampus. Neuroscience. 1986 Nov;19(3):857–872. doi: 10.1016/0306-4522(86)90304-0. [DOI] [PubMed] [Google Scholar]
  17. Hertz L. Functional interactions between neurons and astrocytes I. Turnover and metabolism of putative amino acid transmitters. Prog Neurobiol. 1979;13(3):277–323. doi: 10.1016/0301-0082(79)90018-2. [DOI] [PubMed] [Google Scholar]
  18. Hines M. A program for simulation of nerve equations with branching geometries. Int J Biomed Comput. 1989 Mar;24(1):55–68. doi: 10.1016/0020-7101(89)90007-x. [DOI] [PubMed] [Google Scholar]
  19. Huguenard J. R., Prince D. A. Clonazepam suppresses GABAB-mediated inhibition in thalamic relay neurons through effects in nucleus reticularis. J Neurophysiol. 1994 Jun;71(6):2576–2581. doi: 10.1152/jn.1994.71.6.2576. [DOI] [PubMed] [Google Scholar]
  20. Huguenard J. R., Prince D. A. Intrathalamic rhythmicity studied in vitro: nominal T-current modulation causes robust antioscillatory effects. J Neurosci. 1994 Sep;14(9):5485–5502. doi: 10.1523/JNEUROSCI.14-09-05485.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Isaacson J. S., Solís J. M., Nicoll R. A. Local and diffuse synaptic actions of GABA in the hippocampus. Neuron. 1993 Feb;10(2):165–175. doi: 10.1016/0896-6273(93)90308-e. [DOI] [PubMed] [Google Scholar]
  22. Liu X. B., Warren R. A., Jones E. G. Synaptic distribution of afferents from reticular nucleus in ventroposterior nucleus of cat thalamus. J Comp Neurol. 1995 Feb 6;352(2):187–202. doi: 10.1002/cne.903520203. [DOI] [PubMed] [Google Scholar]
  23. Miles R., Wong R. K. Unitary inhibitory synaptic potentials in the guinea-pig hippocampus in vitro. J Physiol. 1984 Nov;356:97–113. doi: 10.1113/jphysiol.1984.sp015455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mody I., De Koninck Y., Otis T. S., Soltesz I. Bridging the cleft at GABA synapses in the brain. Trends Neurosci. 1994 Dec;17(12):517–525. doi: 10.1016/0166-2236(94)90155-4. [DOI] [PubMed] [Google Scholar]
  25. Newberry N. R., Nicoll R. A. Comparison of the action of baclofen with gamma-aminobutyric acid on rat hippocampal pyramidal cells in vitro. J Physiol. 1985 Mar;360:161–185. doi: 10.1113/jphysiol.1985.sp015610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Otis T. S., De Koninck Y., Mody I. Characterization of synaptically elicited GABAB responses using patch-clamp recordings in rat hippocampal slices. J Physiol. 1993 Apr;463:391–407. doi: 10.1113/jphysiol.1993.sp019600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Otis T. S., Mody I. Differential activation of GABAA and GABAB receptors by spontaneously released transmitter. J Neurophysiol. 1992 Jan;67(1):227–235. doi: 10.1152/jn.1992.67.1.227. [DOI] [PubMed] [Google Scholar]
  28. Otis T. S., Mody I. Modulation of decay kinetics and frequency of GABAA receptor-mediated spontaneous inhibitory postsynaptic currents in hippocampal neurons. Neuroscience. 1992 Jul;49(1):13–32. doi: 10.1016/0306-4522(92)90073-b. [DOI] [PubMed] [Google Scholar]
  29. Soltesz I., Crunelli V. GABAA and pre- and post-synaptic GABAB receptor-mediated responses in the lateral geniculate nucleus. Prog Brain Res. 1992;90:151–169. doi: 10.1016/s0079-6123(08)63613-4. [DOI] [PubMed] [Google Scholar]
  30. Solís J. M., Nicoll R. A. Pharmacological characterization of GABAB-mediated responses in the CA1 region of the rat hippocampal slice. J Neurosci. 1992 Sep;12(9):3466–3472. doi: 10.1523/JNEUROSCI.12-09-03466.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Steriade M., Deschenes M. The thalamus as a neuronal oscillator. Brain Res. 1984 Nov;320(1):1–63. doi: 10.1016/0165-0173(84)90017-1. [DOI] [PubMed] [Google Scholar]
  32. Steriade M., McCormick D. A., Sejnowski T. J. Thalamocortical oscillations in the sleeping and aroused brain. Science. 1993 Oct 29;262(5134):679–685. doi: 10.1126/science.8235588. [DOI] [PubMed] [Google Scholar]
  33. Thompson S. M., Gähwiler B. H. Effects of the GABA uptake inhibitor tiagabine on inhibitory synaptic potentials in rat hippocampal slice cultures. J Neurophysiol. 1992 Jun;67(6):1698–1701. doi: 10.1152/jn.1992.67.6.1698. [DOI] [PubMed] [Google Scholar]
  34. Thompson S. M. Modulation of inhibitory synaptic transmission in the hippocampus. Prog Neurobiol. 1994 Apr;42(5):575–609. doi: 10.1016/0301-0082(94)90044-2. [DOI] [PubMed] [Google Scholar]
  35. VanDongen A. M., Codina J., Olate J., Mattera R., Joho R., Birnbaumer L., Brown A. M. Newly identified brain potassium channels gated by the guanine nucleotide binding protein Go. Science. 1988 Dec 9;242(4884):1433–1437. doi: 10.1126/science.3144040. [DOI] [PubMed] [Google Scholar]
  36. Yamada M., Jahangir A., Hosoya Y., Inanobe A., Katada T., Kurachi Y. GK* and brain G beta gamma activate muscarinic K+ channel through the same mechanism. J Biol Chem. 1993 Nov 25;268(33):24551–24554. [PubMed] [Google Scholar]
  37. von Krosigk M., Bal T., McCormick D. A. Cellular mechanisms of a synchronized oscillation in the thalamus. Science. 1993 Jul 16;261(5119):361–364. doi: 10.1126/science.8392750. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES