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. 1989 Feb;409:191–206. doi: 10.1113/jphysiol.1989.sp017492

Potentiation and suppression by eserine of muscarinic synaptic transmission in the guinea-pig hippocampal slice.

U Misgeld 1, W Müller 1, H R Polder 1
PMCID: PMC1190439  PMID: 2555475

Abstract

1. The effects of the anticholinesterase eserine on CA3 pyramidal cells and dentate gyrus granule cells in guinea-pig hippocampal slices were investigated with single-electrode current-clamp and voltage-clamp recording. 2. In the majority of cells superfused with eserine (0.5-10 microM) for 3-10 min, tetanic stimulation near the cell layers elicited a delayed depolarization (slow EPSP; duration up to 60 s) at a pre-stimulation membrane potential of -60 mV. The slow EPSP was blocked by atropine (1 microM). 3. Under voltage clamp at -60 mV holding potential, an apparent inward current (slow EPSC) with a similar time course to the slow EPSP was observed. 4. The amplitude of the delayed inward current was about 50 pA. The amplitude increased at holding potentials more positive than -60 mV. At holding potentials negative to -60 mV, the delayed inward current was too small to allow reliable analysis. In the absence of eserine, there was a delayed inward current, which was rather small, however, due to a superimposed outward current. 5. Eserine reduced the after-hyperpolarization following a train of action potentials. This effect was antagonized by atropine, but not to pirenzepine. In voltage-clamp recording, eserine reduced a current termed IAHP. 6. CA3 neurones treated with eserine exhibited a region of negative slope conductance (in tetrodotoxin). The slow inward current which developed at clamp potentials between -50 and -40 mV was reduced by Ni2+ (50 microM). The effect of eserine on slope conductance increased with time of exposure. In all neurones superfused with eserine for more than 60 min, burst discharges were observed. Burst discharges were blocked by atropine and Ni2+, but not by pirenzepine. 7. In cells superfused with eserine for more than 1 h, tetanic stimulation failed to elicit a slow EPSP or EPSC. Currents induced by focal acetylcholine (ACh) application were first enhanced by eserine, but blocked after exposure to eserine for more than 1 h. Blockade of ACh-induced currents was also observed after bath application of carbachol (CCh) in a concentration (0.2 microM) in which it did not induce an inward current at -60 mV holding potential. Further, the slow EPSP faded when elicited by repeated tetanic stimulation. 8. While the observed effects of eserine on hippocampal neurones can be explained by eserine's well-known ability to block acetylcholinesterase activity, our data indicate that the effects of eserine involve more than one muscarinic receptor site, i.e. desensitizing and non-desensitizing postsynaptic receptor sites.

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Selected References

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  1. Adams P. R., Jones S. W., Pennefather P., Brown D. A., Koch C., Lancaster B. Slow synaptic transmission in frog sympathetic ganglia. J Exp Biol. 1986 Sep;124:259–285. doi: 10.1242/jeb.124.1.259. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Benardo L. S., Prince D. A. Ionic mechanisms of cholinergic excitation in mammalian hippocampal pyramidal cells. Brain Res. 1982 Oct 14;249(2):333–344. doi: 10.1016/0006-8993(82)90067-1. [DOI] [PubMed] [Google Scholar]
  4. Benson D. M., Blitzer R. D., Landau E. M. An analysis of the depolarization produced in guinea-pig hippocampus by cholinergic receptor stimulation. J Physiol. 1988 Oct;404:479–496. doi: 10.1113/jphysiol.1988.sp017301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bornstein J. C. The effects of physostigmine on synaptic transmission in the inferior mesenteric ganglion of guinea-pigs. J Physiol. 1974 Sep;241(2):309–325. doi: 10.1113/jphysiol.1974.sp010658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cioffi C. L., el-Fakahany E. E. Short-term desensitization of muscarinic cholinergic receptors in mouse neuroblastoma cells: selective loss of agonist low-affinity and pirenzepine high-affinity binding sites. J Pharmacol Exp Ther. 1986 Sep;238(3):916–923. [PubMed] [Google Scholar]
  7. Cole A. E., Nicoll R. A. Acetylcholine mediates a slow synaptic potential in hippocampal pyramidal cells. Science. 1983 Sep 23;221(4617):1299–1301. doi: 10.1126/science.6612345. [DOI] [PubMed] [Google Scholar]
  8. Cole A. E., Nicoll R. A. Characterization of a slow cholinergic post-synaptic potential recorded in vitro from rat hippocampal pyramidal cells. J Physiol. 1984 Jul;352:173–188. doi: 10.1113/jphysiol.1984.sp015285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Constanti A., Galvan M. Fast inward-rectifying current accounts for anomalous rectification in olfactory cortex neurones. J Physiol. 1983 Feb;335:153–178. doi: 10.1113/jphysiol.1983.sp014526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Curtis D. R., Ryall R. W. The excitation of Renshaw cells by cholinomimetics. Exp Brain Res. 1966;2(1):49–65. doi: 10.1007/BF00234360. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Eccles J. C. The nature of synaptic transmission in a sympathetic ganglion. J Physiol. 1944 Jun 15;103(1):27–54. doi: 10.1113/jphysiol.1944.sp004061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Frotscher M., Léránth C. Cholinergic innervation of the rat hippocampus as revealed by choline acetyltransferase immunocytochemistry: a combined light and electron microscopic study. J Comp Neurol. 1985 Sep 8;239(2):237–246. doi: 10.1002/cne.902390210. [DOI] [PubMed] [Google Scholar]
  14. Gage F. H., Björklund A., Stenevi U. Reinnervation of the partially deafferented hippocampus by compensatory collateral sprouting from spared cholinergic and noradrenergic afferents. Brain Res. 1983 May 23;268(1):27–37. doi: 10.1016/0006-8993(83)90387-6. [DOI] [PubMed] [Google Scholar]
  15. Gahwiler B. H., Brown D. A. Functional innervation of cultured hippocampal neurones by cholinergic afferents from co-cultured septal explants. Nature. 1985 Feb 14;313(6003):577–579. doi: 10.1038/313577a0. [DOI] [PubMed] [Google Scholar]
  16. Hablitz J. J., Thalmann R. H. Conductance changes underlying a late synaptic hyperpolarization in hippocampal CA3 neurons. J Neurophysiol. 1987 Jul;58(1):160–179. doi: 10.1152/jn.1987.58.1.160. [DOI] [PubMed] [Google Scholar]
  17. Hadházy P., Szerb J. C. The effect of cholinergic drugs on [3H]acetylcholine release from slices of rat hippocampus, striatum and cortex. Brain Res. 1977 Mar 11;123(2):311–322. doi: 10.1016/0006-8993(77)90482-6. [DOI] [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. Hammer R., Berrie C. P., Birdsall N. J., Burgen A. S., Hulme E. C. Pirenzepine distinguishes between different subclasses of muscarinic receptors. Nature. 1980 Jan 3;283(5742):90–92. doi: 10.1038/283090a0. [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. Houser C. R., Crawford G. D., Barber R. P., Salvaterra P. M., Vaughn J. E. Organization and morphological characteristics of cholinergic neurons: an immunocytochemical study with a monoclonal antibody to choline acetyltransferase. Brain Res. 1983 Apr 25;266(1):97–119. doi: 10.1016/0006-8993(83)91312-4. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. KAMIJO K., KOELLE G. B. The relationship between cholinesterase inhibition and ganglionic transmission. J Pharmacol Exp Ther. 1952 Jul;105(3):349–357. [PubMed] [Google Scholar]
  24. KATZ B., THESLEFF S. A study of the desensitization produced by acetylcholine at the motor end-plate. J Physiol. 1957 Aug 29;138(1):63–80. doi: 10.1113/jphysiol.1957.sp005838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. KOPPANYI T., KARCZMAR A. Contribution to the study of the mechanism of action of cholinesterase inhibitors. J Pharmacol Exp Ther. 1951 Apr;101(4):327–344. [PubMed] [Google Scholar]
  26. Lancaster B., Adams P. R. Calcium-dependent current generating the afterhyperpolarization of hippocampal neurons. J Neurophysiol. 1986 Jun;55(6):1268–1282. doi: 10.1152/jn.1986.55.6.1268. [DOI] [PubMed] [Google Scholar]
  27. Lewis P. R., Shute C. C. The cholinergic limbic system: projections to hippocampal formation, medial cortex, nuclei of the ascending cholinergic reticular system, and the subfornical organ and supra-optic crest. Brain. 1967 Sep;90(3):521–540. doi: 10.1093/brain/90.3.521. [DOI] [PubMed] [Google Scholar]
  28. Madison D. V., Lancaster B., Nicoll R. A. Voltage clamp analysis of cholinergic action in the hippocampus. J Neurosci. 1987 Mar;7(3):733–741. doi: 10.1523/JNEUROSCI.07-03-00733.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Misgeld U., Deisz R. A., Dodt H. U., Lux H. D. The role of chloride transport in postsynaptic inhibition of hippocampal neurons. Science. 1986 Jun 13;232(4756):1413–1415. doi: 10.1126/science.2424084. [DOI] [PubMed] [Google Scholar]
  30. Misgeld U., Frotscher M. Postsynaptic-GABAergic inhibition of non-pyramidal neurons in the guinea-pig hippocampus. Neuroscience. 1986 Sep;19(1):193–206. doi: 10.1016/0306-4522(86)90015-1. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Mo N., Dun N. J., Karczmar A. G. Facilitation and inhibition of nicotinic transmission by eserine in the sympathetic ganglia of the rabbit. Neuropharmacology. 1985 Nov;24(11):1093–1101. doi: 10.1016/0028-3908(85)90197-2. [DOI] [PubMed] [Google Scholar]
  33. Mulder A. H., Yamamura H. I., Kuhar M. J., Snyder S. H. Release of acetylcholine from hippocampal slices by potassium depolarization: dependence on high affinity choline uptake. Brain Res. 1974 Apr 19;70(2):372–376. doi: 10.1016/0006-8993(74)90329-1. [DOI] [PubMed] [Google Scholar]
  34. Müller W., Misgeld U., Heinemann U. Carbachol effects on hippocampal neurons in vitro: dependence on the rate of rise of carbachol tissue concentration. Exp Brain Res. 1988;72(2):287–298. doi: 10.1007/BF00250251. [DOI] [PubMed] [Google Scholar]
  35. Müller W., Misgeld U. Slow cholinergic excitation of guinea pig hippocampal neurons is mediated by two muscarinic receptor subtypes. Neurosci Lett. 1986 Jun 18;67(2):107–112. doi: 10.1016/0304-3940(86)90381-2. [DOI] [PubMed] [Google Scholar]
  36. Nakajima Y., Nakajima S., Leonard R. J., Yamaguchi K. Acetylcholine raises excitability by inhibiting the fast transient potassium current in cultured hippocampal neurons. Proc Natl Acad Sci U S A. 1986 May;83(9):3022–3026. doi: 10.1073/pnas.83.9.3022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Segal M. Synaptic activation of a cholinergic receptor in rat hippocampus. Brain Res. 1988 Jun 14;452(1-2):79–86. doi: 10.1016/0006-8993(88)90011-x. [DOI] [PubMed] [Google Scholar]
  38. Shaw K. P., Aracava Y., Akaike A., Daly J. W., Rickett D. L., Albuquerque E. X. The reversible cholinesterase inhibitor physostigmine has channel-blocking and agonist effects on the acetylcholine receptor-ion channel complex. Mol Pharmacol. 1985 Dec;28(6):527–538. [PubMed] [Google Scholar]
  39. Swandulla D., Armstrong C. M. Fast-deactivating calcium channels in chick sensory neurons. J Gen Physiol. 1988 Aug;92(2):197–218. doi: 10.1085/jgp.92.2.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. VOLLE R. L., KOELLE G. B. The physiological role of acetyl-cholinesterase (AChE) in sympathetic ganglia. J Pharmacol Exp Ther. 1961 Aug;133:223–240. [PubMed] [Google Scholar]
  41. Yaari Y., Hamon B., Lux H. D. Development of two types of calcium channels in cultured mammalian hippocampal neurons. Science. 1987 Feb 6;235(4789):680–682. doi: 10.1126/science.2433765. [DOI] [PubMed] [Google Scholar]

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