Skip to main content
The Journal of Physiology logoLink to The Journal of Physiology
. 1984 Jun;351:327–342. doi: 10.1113/jphysiol.1984.sp015248

The reversal potential of excitatory amino acid action on granule cells of the rat dentate gyrus.

V Crunelli, S Forda, J S Kelly
PMCID: PMC1193120  PMID: 6379151

Abstract

The responses of granule cells to glutamate, aspartate, N-methyl-D-aspartate (NMDA), quisqualate and kainate applied by ionophoresis on to their dendrites in the middle molecular layer of the dentate gyrus were studied with intracellular electrodes using an in vitro hippocampal slice preparation. On passive depolarization 75% of the granule cells displayed anomalous rectification, which persisted in the presence of TTX and TEA but was eliminated by Co2+ or the intracellular injection of Cs+. Short ionophoretic applications of all the excitatory amino acids evoked dose-dependent depolarizations that were highly localized: movement of the ionophoretic electrode by as little as 10 microns could substantially change the size of the response. The depolarizations evoked by glutamate, asparatate, quisqualate and kainate were unaffected by TTX and Co2+. The depolarization evoked by NMDA was unaffected by TTX but markedly reduced by Co2+. Following intracellular injection of Cs+, neurones could be depolarized to +30 mV and the depolarizations produced by glutamate, quisqualate, NMDA and kainate reversed. The reversal potentials (E) were Eglutamate: -5.6 +/- 0.4 mV; ENMDA: 1.8 +/- 1.9 mV; Equisqualate: -3.9 +/- 1.9 mV; Ekainate: -4.6 +/- 2.0 mV. The excitatory post-synaptic potential (e.p.s.p.) evoked by stimulation of the medial perforant path could also be reversed and Ee.p.s.p. was -5.5 +/- 1.1 mV. The 6 mV difference between ENMDA and the equilibrium potential for the other exogenously applied excitatory amino acids and the statistically significant difference between ENMDA and Ee.p.s.p. (P less than 0.005; d.f.: 7) is consistent with our earlier hypothesis that both the transmitter released by the medial perforant path and exogenously applied glutamate are unlikely to interact with NMDA receptors.

Full text

PDF
327

Selected References

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

  1. Ault B., Evans R. H., Francis A. A., Oakes D. J., Watkins J. C. Selective depression of excitatory amino acid induced depolarizations by magnesium ions in isolated spinal cord preparations. J Physiol. 1980 Oct;307:413–428. doi: 10.1113/jphysiol.1980.sp013443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnes C. A., McNaughton B. L. Physiological compensation for loss of afferent synapses in rat hippocampal granule cells during senescence. J Physiol. 1980 Dec;309:473–485. doi: 10.1113/jphysiol.1980.sp013521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barrett E. F., Barrett J. N., Crill W. E. Voltage-sensitive outward currents in cat motoneurones. J Physiol. 1980 Jul;304:251–276. doi: 10.1113/jphysiol.1980.sp013323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benardo L. S., Prince D. A. Acetylcholine induced modulation of hippocampal pyramidal neurons. Brain Res. 1981 Apr 27;211(1):227–234. doi: 10.1016/0006-8993(81)90089-5. [DOI] [PubMed] [Google Scholar]
  5. Bezanilla F., Armstrong C. M. Negative conductance caused by entry of sodium and cesium ions into the potassium channels of squid axons. J Gen Physiol. 1972 Nov;60(5):588–608. doi: 10.1085/jgp.60.5.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brown D. A., Griffith W. H. Calcium-activated outward current in voltage-clamped hippocampal neurones of the guinea-pig. J Physiol. 1983 Apr;337:287–301. doi: 10.1113/jphysiol.1983.sp014624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brown T. H., Fricke R. A., Perkel D. H. Passive electrical constants in three classes of hippocampal neurons. J Neurophysiol. 1981 Oct;46(4):812–827. doi: 10.1152/jn.1981.46.4.812. [DOI] [PubMed] [Google Scholar]
  8. Brown T. H., Johnston D. Voltage-clamp analysis of mossy fiber synaptic input to hippocampal neurons. J Neurophysiol. 1983 Aug;50(2):487–507. doi: 10.1152/jn.1983.50.2.487. [DOI] [PubMed] [Google Scholar]
  9. Constanti A., Connor J. D., Galvan M., Nistri A. Intracellularly-recorded effects of glutamate and aspartate on neurones in the guinea-pig olfactory cortex slice. Brain Res. 1980 Aug 18;195(2):403–420. doi: 10.1016/0006-8993(80)90075-x. [DOI] [PubMed] [Google Scholar]
  10. Crunelli V., Forda S., Brooks P. A., Wilson K. C., Wise J. C., Kelly J. S. Passive membrane properties of neurones in the dorsal raphe and periaqueductal grey recorded in vitro. Neurosci Lett. 1983 Oct 10;40(3):263–268. doi: 10.1016/0304-3940(83)90049-6. [DOI] [PubMed] [Google Scholar]
  11. Crunelli V., Forda S., Collingridge G. L., Kelly J. S. Intracellular recorded synaptic antagonism in the rat dentate gyrus. Nature. 1982 Dec 2;300(5891):450–452. doi: 10.1038/300450a0. [DOI] [PubMed] [Google Scholar]
  12. Crunelli V., Forda S., Kelly J. S. Blockade of amino acid-induced depolarizations and inhibition of excitatory post-synaptic potentials in rat dentate gyrus. J Physiol. 1983 Aug;341:627–640. doi: 10.1113/jphysiol.1983.sp014829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dingledine R. N-methyl aspartate activates voltage-dependent calcium conductance in rat hippocampal pyramidal cells. J Physiol. 1983 Oct;343:385–405. doi: 10.1113/jphysiol.1983.sp014899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dodd J., Dingledine R., Kelly J. S. The excitatory action of acetylcholine on hippocampal neurones of the guinea pig and rat maintained in vitro. Brain Res. 1981 Feb 23;207(1):109–127. doi: 10.1016/0006-8993(81)90682-x. [DOI] [PubMed] [Google Scholar]
  15. Engberg I., Flatman J. A., Lambert J. D. The action of N-methyl-D-aspartic and kainic acids on motoneurones with emphasis on conductance changes [proceedings]. Br J Pharmacol. 1978 Nov;64(3):384P–385P. [PMC free article] [PubMed] [Google Scholar]
  16. Engberg I., Flatman J. A., Lambert J. D. The actions of excitatory amino acids on motoneurones in the feline spinal cord. J Physiol. 1979 Mar;288:227–261. [PMC free article] [PubMed] [Google Scholar]
  17. Hablitz J. J., Langmoen I. A. Excitation of hippocampal pyramidal cells by glutamate in the guinea-pig and rat. J Physiol. 1982 Apr;325:317–331. doi: 10.1113/jphysiol.1982.sp014152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Halliwell J. V., Adams P. R. Voltage-clamp analysis of muscarinic excitation in hippocampal neurons. Brain Res. 1982 Oct 28;250(1):71–92. doi: 10.1016/0006-8993(82)90954-4. [DOI] [PubMed] [Google Scholar]
  19. Hotson J. R., Prince D. A. A calcium-activated hyperpolarization follows repetitive firing in hippocampal neurons. J Neurophysiol. 1980 Feb;43(2):409–419. doi: 10.1152/jn.1980.43.2.409. [DOI] [PubMed] [Google Scholar]
  20. Hotson J. R., Prince D. A., Schwartzkroin P. A. Anomalous inward rectification in hippocampal neurons. J Neurophysiol. 1979 May;42(3):889–895. doi: 10.1152/jn.1979.42.3.889. [DOI] [PubMed] [Google Scholar]
  21. Jefferys J. G. Initiation and spread of action potentials in granule cells maintained in vitro in slices of guinea-pig hippocampus. J Physiol. 1979 Apr;289:375–388. doi: 10.1113/jphysiol.1979.sp012742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Johnston D., Brown T. H. Interpretation of voltage-clamp measurements in hippocampal neurons. J Neurophysiol. 1983 Aug;50(2):464–486. doi: 10.1152/jn.1983.50.2.464. [DOI] [PubMed] [Google Scholar]
  23. Johnston D., Hablitz J. J., Wilson W. A. Voltage clamp discloses slow inward current in hippocampal burst-firing neurones. Nature. 1980 Jul 24;286(5771):391–393. doi: 10.1038/286391a0. [DOI] [PubMed] [Google Scholar]
  24. Krnjević K., Pumain R., Renaud L. The mechanism of excitation by acetylcholine in the cerebral cortex. J Physiol. 1971 May;215(1):247–268. doi: 10.1113/jphysiol.1971.sp009467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lomo T. Patterns of activation in a monosynaptic cortical pathway: the perforant path input to the dentate area of the hippocampal formation. Exp Brain Res. 1971;12(1):18–45. [PubMed] [Google Scholar]
  26. MacDonald J. F., Porietis A. V. DL-quisqualic and L-aspartic acids activate separate excitatory conductances in cultured spinal cord neurons. Brain Res. 1982 Aug 5;245(1):175–178. doi: 10.1016/0006-8993(82)90356-0. [DOI] [PubMed] [Google Scholar]
  27. MacDonald J. F., Porietis A. V., Wojtowicz J. M. L-Aspartic acid induces a region of negative slope conductance in the current-voltage relationship of cultured spinal cord neurons. Brain Res. 1982 Apr 8;237(1):248–253. doi: 10.1016/0006-8993(82)90575-3. [DOI] [PubMed] [Google Scholar]
  28. Matthews G., Wickelgren W. O. Glutamate and synaptic excitation of reticulospinal neurones of lamprey. J Physiol. 1979 Aug;293:417–433. doi: 10.1113/jphysiol.1979.sp012897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. McNaughton B. L. Evidence for two physiologically distinct perforant pathways to the fascia dentata. Brain Res. 1980 Oct 13;199(1):1–19. doi: 10.1016/0006-8993(80)90226-7. [DOI] [PubMed] [Google Scholar]
  30. Nicoll R. A., Alger B. E. Synaptic excitation may activate a calcium-dependent potassium conductance in hippocampal pyramidal cells. Science. 1981 May 22;212(4497):957–959. doi: 10.1126/science.6262912. [DOI] [PubMed] [Google Scholar]
  31. Puil E. S-Glutamate: its interactions with spinal neurons. Brain Res. 1981 Dec;228(3):229–322. doi: 10.1016/0165-0173(81)90007-2. [DOI] [PubMed] [Google Scholar]
  32. Robinson J. H., Deadwyler S. A. Kainic acid produces depolarization of CA3 pyramidal cells in the vitro hippocampal slice. Brain Res. 1981 Sep 21;221(1):117–127. doi: 10.1016/0006-8993(81)91067-2. [DOI] [PubMed] [Google Scholar]
  33. Steward O. Topographic organization of the projections from the entorhinal area to the hippocampal formation of the rat. J Comp Neurol. 1976 Jun 1;167(3):285–314. doi: 10.1002/cne.901670303. [DOI] [PubMed] [Google Scholar]
  34. Storm-Mathisen J., Iversen L. L. Uptake of [3H]Glutamic acid in excitatory nerve endings: light and electronmicroscopic observations in the hippocampal formation of the rat. Neuroscience. 1979;4(9):1237–1253. doi: 10.1016/0306-4522(79)90154-4. [DOI] [PubMed] [Google Scholar]
  35. Thalmann R. H., Ayala G. F. A late increase in potassium conductance follows synaptic stimulation of granule neurons of the dentate gyrus. Neurosci Lett. 1982 Apr 26;29(3):243–248. doi: 10.1016/0304-3940(82)90324-x. [DOI] [PubMed] [Google Scholar]
  36. Tillotson D. Inactivation of Ca conductance dependent on entry of Ca ions in molluscan neurons. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1497–1500. doi: 10.1073/pnas.76.3.1497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Watkins J. C., Evans R. H. Excitatory amino acid transmitters. Annu Rev Pharmacol Toxicol. 1981;21:165–204. doi: 10.1146/annurev.pa.21.040181.001121. [DOI] [PubMed] [Google Scholar]
  38. Wheal H. V., Miller J. J. Pharmacological identification of acetylcholine and glutamate excitatory systems in the dentate gyrus of the rat. Brain Res. 1980 Jan 20;182(1):145–155. doi: 10.1016/0006-8993(80)90837-9. [DOI] [PubMed] [Google Scholar]
  39. White W. F., Nadler J. V., Hamberger A., Cotman C. W., Cummins J. T. Glutamate as transmitter of hippocampal perforant path. Nature. 1977 Nov 24;270(5635):356–357. doi: 10.1038/270356a0. [DOI] [PubMed] [Google Scholar]
  40. Wojtowicz J. M., Gysen M., MacDonald J. F. Multiple reversal potentials for responses to L-glutamic acid. Brain Res. 1981 May 25;213(1):195–200. doi: 10.1016/0006-8993(81)91261-0. [DOI] [PubMed] [Google Scholar]
  41. Zieglgänsberger W., Puil E. A. Actions of glutamic acid on spinal neurones. Exp Brain Res. 1973 Mar 29;17(1):35–49. doi: 10.1007/BF00234562. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES