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. 1994 Apr 12;91(8):3058–3062. doi: 10.1073/pnas.91.8.3058

Synaptic disinhibition during maintenance of long-term potentiation in the CA1 hippocampal subfield.

A Stelzer 1, G Simon 1, G Kovacs 1, R Rai 1
PMCID: PMC43514  PMID: 8159706

Abstract

Long-term potentiation (LTP) in the CA1 region of the hippocampus is widely believed to occur through a strengthening of efficacy of excitatory synapses between afferent fibers and pyramidal cells. An alternative mechanism of LTP, reduction of efficacy of synaptic inhibition, was examined in the present report. The present study demonstrates that the maintenance of LTP in the CA1 hippocampal subfield of guinea pigs is accompanied by impairment of type A gamma-aminobutyric acid (GABA) receptor function, particularly at apical dendritic sites of CA1 pyramidal cells. Enhanced excitability of GABAergic interneurons during LTP represents a strengthening of inhibitory efficacy. The net effect of opposite modifications of synaptic inhibition during LTP of CA1 pyramidal cells is an overall impairment of the strength of GABAergic inhibition, and disinhibition could contribute importantly to CA1 pyramidal cell LTP.

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Selected References

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

  1. Abraham W. C., Gustafsson B., Wigström H. Long-term potentiation involves enhanced synaptic excitation relative to synaptic inhibition in guinea-pig hippocampus. J Physiol. 1987 Dec;394:367–380. doi: 10.1113/jphysiol.1987.sp016875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alger B. E., Nicoll R. A. Spontaneous inhibitory post-synaptic potentials in hippocampus: mechanism for tonic inhibition. Brain Res. 1980 Oct 27;200(1):195–200. doi: 10.1016/0006-8993(80)91108-7. [DOI] [PubMed] [Google Scholar]
  3. Bekkers J. M., Stevens C. F. Presynaptic mechanism for long-term potentiation in the hippocampus. Nature. 1990 Aug 23;346(6286):724–729. doi: 10.1038/346724a0. [DOI] [PubMed] [Google Scholar]
  4. Benardo L. S., Masukawa L. M., Prince D. A. Electrophysiology of isolated hippocampal pyramidal dendrites. J Neurosci. 1982 Nov;2(11):1614–1622. doi: 10.1523/JNEUROSCI.02-11-01614.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Buzsáki G., Eidelberg E. Direct afferent excitation and long-term potentiation of hippocampal interneurons. J Neurophysiol. 1982 Sep;48(3):597–607. doi: 10.1152/jn.1982.48.3.597. [DOI] [PubMed] [Google Scholar]
  6. COOMBS J. S., ECCLES J. C., FATT P. The inhibitory suppression of reflex discharges from motoneurones. J Physiol. 1955 Nov 28;130(2):396–413. doi: 10.1113/jphysiol.1955.sp005414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Collingridge G. L., Kehl S. J., McLennan H. Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus. J Physiol. 1983 Jan;334:33–46. doi: 10.1113/jphysiol.1983.sp014478. [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. Davies C. H., Starkey S. J., Pozza M. F., Collingridge G. L. GABA autoreceptors regulate the induction of LTP. Nature. 1991 Feb 14;349(6310):609–611. doi: 10.1038/349609a0. [DOI] [PubMed] [Google Scholar]
  10. Davies S. N., Lester R. A., Reymann K. G., Collingridge G. L. Temporally distinct pre- and post-synaptic mechanisms maintain long-term potentiation. Nature. 1989 Apr 6;338(6215):500–503. doi: 10.1038/338500a0. [DOI] [PubMed] [Google Scholar]
  11. Dingledine R., Gjerstad L. Reduced inhibition during epileptiform activity in the in vitro hippocampal slice. J Physiol. 1980 Aug;305:297–313. doi: 10.1113/jphysiol.1980.sp013364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dolphin A. C., Errington M. L., Bliss T. V. Long-term potentiation of the perforant path in vivo is associated with increased glutamate release. Nature. 1982 Jun 10;297(5866):496–498. doi: 10.1038/297496a0. [DOI] [PubMed] [Google Scholar]
  13. HAMLYN L. H. An electron microscope study of pyramidal neurons in the Ammon's horn of the rabbit. J Anat. 1963 Apr;97:189–201. [PMC free article] [PubMed] [Google Scholar]
  14. Haas H. L., Rose G. Long-term potentiation of excitatory synaptic transmission in the rat hippocampus: the role of inhibitory processes. J Physiol. 1982 Aug;329:541–552. doi: 10.1113/jphysiol.1982.sp014318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kairiss E. W., Abraham W. C., Bilkey D. K., Goddard G. V. Field potential evidence for long-term potentiation of feed-forward inhibition in the rat dentate gyrus. Brain Res. 1987 Jan 13;401(1):87–94. doi: 10.1016/0006-8993(87)91167-x. [DOI] [PubMed] [Google Scholar]
  16. Kunkel D. D., Scharfman H. E., Schmiege D. L., Schwartzkroin P. A. Electron microscopy of intracellularly labeled neurons in the hippocampal slice preparation. Microsc Res Tech. 1993 Jan 1;24(1):67–84. doi: 10.1002/jemt.1070240107. [DOI] [PubMed] [Google Scholar]
  17. Lacaille J. C., Schwartzkroin P. A. Stratum lacunosum-moleculare interneurons of hippocampal CA1 region. II. Intrasomatic and intradendritic recordings of local circuit synaptic interactions. J Neurosci. 1988 Apr;8(4):1411–1424. doi: 10.1523/JNEUROSCI.08-04-01411.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Malinow R., Tsien R. W. Presynaptic enhancement shown by whole-cell recordings of long-term potentiation in hippocampal slices. Nature. 1990 Jul 12;346(6280):177–180. doi: 10.1038/346177a0. [DOI] [PubMed] [Google Scholar]
  19. Manabe T., Renner P., Nicoll R. A. Postsynaptic contribution to long-term potentiation revealed by the analysis of miniature synaptic currents. Nature. 1992 Jan 2;355(6355):50–55. doi: 10.1038/355050a0. [DOI] [PubMed] [Google Scholar]
  20. McCarren M., Alger B. E. Use-dependent depression of IPSPs in rat hippocampal pyramidal cells in vitro. J Neurophysiol. 1985 Feb;53(2):557–571. doi: 10.1152/jn.1985.53.2.557. [DOI] [PubMed] [Google Scholar]
  21. Miles R., Wong R. K. Latent synaptic pathways revealed after tetanic stimulation in the hippocampus. Nature. 1987 Oct 22;329(6141):724–726. doi: 10.1038/329724a0. [DOI] [PubMed] [Google Scholar]
  22. Misgeld U., Sarvey J. M., Klee M. R. Heterosynaptic postactivation potentiation in hippocampal CA 3 neurons: long-term changes of the postsynaptic potentials. Exp Brain Res. 1979 Oct;37(2):217–229. doi: 10.1007/BF00237709. [DOI] [PubMed] [Google Scholar]
  23. Rall W. Distinguishing theoretical synaptic potentials computed for different soma-dendritic distributions of synaptic input. J Neurophysiol. 1967 Sep;30(5):1138–1168. doi: 10.1152/jn.1967.30.5.1138. [DOI] [PubMed] [Google Scholar]
  24. Scharfman H. E., Sarvey J. M. gamma-Aminobutyrate sensitivity does not change during long-term potentiation in rat hippocampal slices. Neuroscience. 1985 Jul;15(3):695–702. doi: 10.1016/0306-4522(85)90071-5. [DOI] [PubMed] [Google Scholar]
  25. Scharfman H. E. Spiny neurons of area CA3c in rat hippocampal slices have similar electrophysiological characteristics and synaptic responses despite morphological variation. Hippocampus. 1993 Jan;3(1):9–28. doi: 10.1002/hipo.450030103. [DOI] [PubMed] [Google Scholar]
  26. Schwartzkroin P. A. Characteristics of CA1 neurons recorded intracellularly in the hippocampal in vitro slice preparation. Brain Res. 1975 Mar 7;85(3):423–436. doi: 10.1016/0006-8993(75)90817-3. [DOI] [PubMed] [Google Scholar]
  27. Stelzer A., Slater N. T., ten Bruggencate G. Activation of NMDA receptors blocks GABAergic inhibition in an in vitro model of epilepsy. Nature. 1987 Apr 16;326(6114):698–701. doi: 10.1038/326698a0. [DOI] [PubMed] [Google Scholar]
  28. Stewart W. W. Functional connections between cells as revealed by dye-coupling with a highly fluorescent naphthalimide tracer. Cell. 1978 Jul;14(3):741–759. doi: 10.1016/0092-8674(78)90256-8. [DOI] [PubMed] [Google Scholar]
  29. Taube J. S., Schwartzkroin P. A. Intracellular recording from hippocampal CA1 interneurons before and after development of long-term potentiation. Brain Res. 1987 Sep 1;419(1-2):32–38. doi: 10.1016/0006-8993(87)90565-8. [DOI] [PubMed] [Google Scholar]
  30. Taube J. S., Schwartzkroin P. A. Mechanisms of long-term potentiation: EPSP/spike dissociation, intradendritic recordings, and glutamate sensitivity. J Neurosci. 1988 May;8(5):1632–1644. doi: 10.1523/JNEUROSCI.08-05-01632.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thompson S. M., Gähwiler B. H. Activity-dependent disinhibition. I. Repetitive stimulation reduces IPSP driving force and conductance in the hippocampus in vitro. J Neurophysiol. 1989 Mar;61(3):501–511. doi: 10.1152/jn.1989.61.3.501. [DOI] [PubMed] [Google Scholar]
  32. Traub R. D., Wong R. K. Cellular mechanism of neuronal synchronization in epilepsy. Science. 1982 May 14;216(4547):745–747. doi: 10.1126/science.7079735. [DOI] [PubMed] [Google Scholar]
  33. Wong R. K., Prince D. A., Basbaum A. I. Intradendritic recordings from hippocampal neurons. Proc Natl Acad Sci U S A. 1979 Feb;76(2):986–990. doi: 10.1073/pnas.76.2.986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yamamoto C., Chujo T. Long-term potentiation in thin hippocampal sections studied by intracellular and extracellular recordings. Exp Neurol. 1978 Jan 15;58(2):242–250. doi: 10.1016/0014-4886(78)90137-1. [DOI] [PubMed] [Google Scholar]
  35. Yamamoto C. Intracellular study of seizure-like afterdischarges elicited in thin hippocampal sections in vitro. Exp Neurol. 1972 Apr;35(1):154–164. doi: 10.1016/0014-4886(72)90066-0. [DOI] [PubMed] [Google Scholar]

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