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. 1997 Dec 1;505(Pt 2):307–317. doi: 10.1111/j.1469-7793.1997.307bb.x

Sr2+ supports depolarization-induced suppression of inhibition and provides new evidence for a presynaptic expression mechanism in rat hippocampal slices.

W Morishita 1, B E Alger 1
PMCID: PMC1160065  PMID: 9423174

Abstract

1. We studied the transient suppression of evoked GABAA ergic inhibitory postsynaptic currents (eIPSCs) that follows brief membrane depolarization in rat CA1 hippocampal pyramidal cells, a process called depolarization-induced suppression of inhibition (DSI). We used whole-cell patch electrodes filled with a CsCl-based solution to voltage clamp the currents. All experiments were done in the presence of 50 microM 2-amino-5-phosphonovaleric acid (APV) and 20 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) to block ionotropic glutamate-induced currents and polysynaptic transmission in the slice preparation. 2. Substituting strontium (Sr2+) for extracellular calcium (Ca2+) led to the appearance of numerous 'asynchronous' small IPSCs following an eIPSC. These asynchronous IPSCs were indistinguishable from TTX-insensitive quantal IPSCs. 3. Although somewhat less effective than Ca2+, Sr2+ was capable of supporting DSI, and both asynchronous and synchronous IPSCs were blocked by the DSI process. 4. During DSI, quantal content of eIPSCs, but not quantal size, was significantly reduced. 5. Sr2+ converted paired-pulse depression (PPD) of eIPSCs to a paired-pulse facilitation (PPF), presumably by altering the probability of release at inhibitory nerve terminals. DSI had no effect on either PPD or PPF. 6. The results show that Sr2+ induces asynchronous release of GABA as it does of other neurotransmitters and changes the probability of release at GABAA ergic terminals as well. Most importantly, the results support the hypothesis that, despite being induced postsynaptically, DSI is expressed presynaptically as a decrease in GABA release, possibly by acting at a site other than the Ca(2+)-dependent release step.

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Selected References

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  1. Abdul-Ghani M. A., Valiante T. A., Pennefather P. S. Sr2+ and quantal events at excitatory synapses between mouse hippocampal neurons in culture. J Physiol. 1996 Aug 15;495(Pt 1):113–125. doi: 10.1113/jphysiol.1996.sp021578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alger B. E., Pitler T. A. Retrograde signaling at GABAA-receptor synapses in the mammalian CNS. Trends Neurosci. 1995 Aug;18(8):333–340. doi: 10.1016/0166-2236(95)93923-l. [DOI] [PubMed] [Google Scholar]
  3. Alger B. E., Pitler T. A., Wagner J. J., Martin L. A., Morishita W., Kirov S. A., Lenz R. A. Retrograde signalling in depolarization-induced suppression of inhibition in rat hippocampal CA1 cells. J Physiol. 1996 Oct 1;496(Pt 1):197–209. doi: 10.1113/jphysiol.1996.sp021677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bain A. I., Quastel D. M. Quantal transmitter release mediated by strontium at the mouse motor nerve terminal. J Physiol. 1992 May;450:63–87. doi: 10.1113/jphysiol.1992.sp019116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blanton M. G., Lo Turco J. J., Kriegstein A. R. Whole cell recording from neurons in slices of reptilian and mammalian cerebral cortex. J Neurosci Methods. 1989 Dec;30(3):203–210. doi: 10.1016/0165-0270(89)90131-3. [DOI] [PubMed] [Google Scholar]
  6. Buhl E. H., Halasy K., Somogyi P. Diverse sources of hippocampal unitary inhibitory postsynaptic potentials and the number of synaptic release sites. Nature. 1994 Apr 28;368(6474):823–828. doi: 10.1038/368823a0. [DOI] [PubMed] [Google Scholar]
  7. Cummings D. D., Wilcox K. S., Dichter M. A. Calcium-dependent paired-pulse facilitation of miniature EPSC frequency accompanies depression of EPSCs at hippocampal synapses in culture. J Neurosci. 1996 Sep 1;16(17):5312–5323. doi: 10.1523/JNEUROSCI.16-17-05312.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Dodge F. A., Jr, Rahamimoff R. Co-operative action a calcium ions in transmitter release at the neuromuscular junction. J Physiol. 1967 Nov;193(2):419–432. doi: 10.1113/jphysiol.1967.sp008367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Freund T. F., Buzsáki G. Interneurons of the hippocampus. Hippocampus. 1996;6(4):347–470. doi: 10.1002/(SICI)1098-1063(1996)6:4<347::AID-HIPO1>3.0.CO;2-I. [DOI] [PubMed] [Google Scholar]
  11. Geppert M., Goda Y., Hammer R. E., Li C., Rosahl T. W., Stevens C. F., Südhof T. C. Synaptotagmin I: a major Ca2+ sensor for transmitter release at a central synapse. Cell. 1994 Nov 18;79(4):717–727. doi: 10.1016/0092-8674(94)90556-8. [DOI] [PubMed] [Google Scholar]
  12. Goda Y., Stevens C. F. Two components of transmitter release at a central synapse. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12942–12946. doi: 10.1073/pnas.91.26.12942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Higashida H., Brown D. A. Two polyphosphatidylinositide metabolites control two K+ currents in a neuronal cell. 1986 Sep 25-Oct 1Nature. 323(6086):333–335. doi: 10.1038/323333a0. [DOI] [PubMed] [Google Scholar]
  14. Hoch D. B., Wilson J. E. Effects of calcium, strontium, and barium ions on phosphorylation of hippocampal proteins in vitro. J Neurochem. 1984 Jan;42(1):54–58. doi: 10.1111/j.1471-4159.1984.tb09697.x. [DOI] [PubMed] [Google Scholar]
  15. Li C., Ullrich B., Zhang J. Z., Anderson R. G., Brose N., Südhof T. C. Ca(2+)-dependent and -independent activities of neural and non-neural synaptotagmins. Nature. 1995 Jun 15;375(6532):594–599. doi: 10.1038/375594a0. [DOI] [PubMed] [Google Scholar]
  16. Llano I., Leresche N., Marty A. Calcium entry increases the sensitivity of cerebellar Purkinje cells to applied GABA and decreases inhibitory synaptic currents. Neuron. 1991 Apr;6(4):565–574. doi: 10.1016/0896-6273(91)90059-9. [DOI] [PubMed] [Google Scholar]
  17. McNamara J. O. Cellular and molecular basis of epilepsy. J Neurosci. 1994 Jun;14(6):3413–3425. doi: 10.1523/JNEUROSCI.14-06-03413.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Miles R., Tóth K., Gulyás A. I., Hájos N., Freund T. F. Differences between somatic and dendritic inhibition in the hippocampus. Neuron. 1996 Apr;16(4):815–823. doi: 10.1016/s0896-6273(00)80101-4. [DOI] [PubMed] [Google Scholar]
  19. Morishita W., Kirov S. A., Pitler T. A., Martin L. A., Lenz R. A., Alger B. E. N-ethylmaleimide blocks depolarization-induced suppression of inhibition and enhances GABA release in the rat hippocampal slice in vitro. J Neurosci. 1997 Feb 1;17(3):941–950. doi: 10.1523/JNEUROSCI.17-03-00941.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nachshen D. A. Regulation of cytosolic calcium concentration in presynaptic nerve endings isolated from rat brain. J Physiol. 1985 Jun;363:87–101. doi: 10.1113/jphysiol.1985.sp015697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nicoll R. A., Alger B. E. A simple chamber for recording from submerged brain slices. J Neurosci Methods. 1981 Aug;4(2):153–156. doi: 10.1016/0165-0270(81)90049-2. [DOI] [PubMed] [Google Scholar]
  22. Oliet S. H., Malenka R. C., Nicoll R. A. Bidirectional control of quantal size by synaptic activity in the hippocampus. Science. 1996 Mar 1;271(5253):1294–1297. doi: 10.1126/science.271.5253.1294. [DOI] [PubMed] [Google Scholar]
  23. Pitler T. A., Alger B. E. Depolarization-induced suppression of GABAergic inhibition in rat hippocampal pyramidal cells: G protein involvement in a presynaptic mechanism. Neuron. 1994 Dec;13(6):1447–1455. doi: 10.1016/0896-6273(94)90430-8. [DOI] [PubMed] [Google Scholar]
  24. Pitler T. A., Alger B. E. Postsynaptic spike firing reduces synaptic GABAA responses in hippocampal pyramidal cells. J Neurosci. 1992 Oct;12(10):4122–4132. doi: 10.1523/JNEUROSCI.12-10-04122.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Silinsky E. M. On the calcium receptor that mediates depolarization-secretion coupling at cholinergic motor nerve terminals. Br J Pharmacol. 1981 Jun;73(2):413–429. doi: 10.1111/j.1476-5381.1981.tb10438.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Silinsky E. M. On the role of barium in supporting the asynchronous release of acetylcholine quanta by motor nerve impulses. J Physiol. 1978 Jan;274:157–171. doi: 10.1113/jphysiol.1978.sp012141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Vincent P., Armstrong C. M., Marty A. Inhibitory synaptic currents in rat cerebellar Purkinje cells: modulation by postsynaptic depolarization. J Physiol. 1992 Oct;456:453–471. doi: 10.1113/jphysiol.1992.sp019346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Vincent P., Marty A. Neighboring cerebellar Purkinje cells communicate via retrograde inhibition of common presynaptic interneurons. Neuron. 1993 Nov;11(5):885–893. doi: 10.1016/0896-6273(93)90118-b. [DOI] [PubMed] [Google Scholar]
  29. Wagner J. J., Alger B. E. Increased neuronal excitability during depolarization-induced suppression of inhibition in rat hippocampus. J Physiol. 1996 Aug 15;495(Pt 1):107–112. doi: 10.1113/jphysiol.1996.sp021577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wigström H., Gustafsson B. Facilitated induction of hippocampal long-lasting potentiation during blockade of inhibition. Nature. 1983 Feb 17;301(5901):603–604. doi: 10.1038/301603a0. [DOI] [PubMed] [Google Scholar]
  31. Wilcox K. S., Dichter M. A. Paired pulse depression in cultured hippocampal neurons is due to a presynaptic mechanism independent of GABAB autoreceptor activation. J Neurosci. 1994 Mar;14(3 Pt 2):1775–1788. doi: 10.1523/JNEUROSCI.14-03-01775.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Zengel J. E., Magleby K. L. Differential effects of Ba2+, Sr2+, and Ca2+ on stimulation-induced changes in transmitter release at the frog neuromuscular junction. J Gen Physiol. 1980 Aug;76(2):175–211. doi: 10.1085/jgp.76.2.175. [DOI] [PMC free article] [PubMed] [Google Scholar]

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