Skip to main content
The Journal of Physiology logoLink to The Journal of Physiology
. 1984 Sep;354:319–331. doi: 10.1113/jphysiol.1984.sp015378

Control of the repetitive discharge of rat CA 1 pyramidal neurones in vitro.

D V Madison, R A Nicoll
PMCID: PMC1193414  PMID: 6434729

Abstract

Experiments using intracellular recording techniques were performed on rat hippocampal neurones in vitro, to study the discharge properties of these cells. When CA 1 pyramidal cells were excited by injecting long depolarizing current pulses (approximately 600-800 ms), they responded with an initial rapid action potential discharge which slowed, or accommodated, and then stopped after 200-300 ms. The train of action potentials was followed by a hyperpolarization which was due primarily to calcium-activated potassium conductance (GK(Ca]. The amplitude of this hyperpolarization increased with an increasing number of action potentials in the initial discharge. Blocking the calcium-activated potassium conductance, by injecting EGTA into the cell, by bathing the cell in cadmium, a calcium channel blocker, or by bathing the cell in calcium-free medium, reduced the after-hyperpolarization (a.h.p.) and accommodation such that the frequency of action potential discharge increased and the duration of this discharge was prolonged. Blocking the calcium-activated potassium conductance had a greater effect on discharge frequency later in the action potential train, as late interspike intervals were shortened more than early ones by the application of cadmium or of calcium-free medium. This was presumably because the calcium-activated potassium conductance was more developed later in the train. Accommodation was not completely abolished in the absence of calcium and presence of cadmium, suggesting that other factors, in addition to calcium-activated potassium conductance, contributed to this process. This remaining accommodation was reduced by low doses of carbachol, suggesting that the M-current also plays a role in accommodation. We conclude that accommodation of the action potential discharge of hippocampal pyramidal cells may be regulated by at least two potassium currents: the calcium-activated potassium current and the M-current. Both of these currents are turned on during excitation of the neurone and act in an inhibitory manner on that neurone to limit further action potential discharge.

Full text

PDF
319

Selected References

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

  1. Adams P. R., Brown D. A., Constanti A. Pharmacological inhibition of the M-current. J Physiol. 1982 Nov;332:223–262. doi: 10.1113/jphysiol.1982.sp014411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adams P. R., Brown D. A. Synaptic inhibition of the M-current: slow excitatory post-synaptic potential mechanism in bullfrog sympathetic neurones. J Physiol. 1982 Nov;332:263–272. doi: 10.1113/jphysiol.1982.sp014412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aldenhoff J. B., Gruol D. L., Rivier J., Vale W., Siggins G. R. Corticotropin releasing factor decreases postburst hyperpolarizations and excites hippocampal neurons. Science. 1983 Aug 26;221(4613):875–877. doi: 10.1126/science.6603658. [DOI] [PubMed] [Google Scholar]
  4. Alger B. E., Nicoll R. A. Epileptiform burst afterhyperolarization: calcium-dependent potassium potential in hippocampal CA1 pyramidal cells. Science. 1980 Dec 5;210(4474):1122–1124. doi: 10.1126/science.7444438. [DOI] [PubMed] [Google Scholar]
  5. Alger B. E., Nicoll R. A. Feed-forward dendritic inhibition in rat hippocampal pyramidal cells studied in vitro. J Physiol. 1982 Jul;328:105–123. doi: 10.1113/jphysiol.1982.sp014255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Baldissera F., Gustafsson B. Firing behaviour of a neurone model based on the afterhyperpolarization conductance time course and algebraical summation. Adaptation and steady state firing. Acta Physiol Scand. 1974 Sep;92(1):27–47. doi: 10.1111/j.1748-1716.1974.tb05720.x. [DOI] [PubMed] [Google Scholar]
  7. Baldissera F., Gustafsson B. Firing behaviour of a neurone model based on the afterhyperpolarization conductance time course. First interval firing. Acta Physiol Scand. 1974 Aug;91(4):528–544. doi: 10.1111/j.1748-1716.1974.tb05708.x. [DOI] [PubMed] [Google Scholar]
  8. Baldissera F., Gustafsson B. Time course and potential dependence of the membrane conductance change during the afterhyperpolarization in the cat's alpha-motoneurones. Brain Res. 1970 Jan 20;17(2):365–368. doi: 10.1016/0006-8993(70)90094-6. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. 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]
  12. Buchert-Rau B., Sonnhof U. An analysis of the epileptogenic potency of CO2+- its ability to induce acute convulsive activity in the isolated frog spinal cord. Pflugers Arch. 1982 Jul;394(1):1–11. doi: 10.1007/BF01108300. [DOI] [PubMed] [Google Scholar]
  13. Calvin W. H., Schwindt P. C. Steps in production of motoneuron spikes during rhythmic firing. J Neurophysiol. 1972 May;35(3):297–310. doi: 10.1152/jn.1972.35.3.297. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Connor J. A., Stevens C. F. Prediction of repetitive firing behaviour from voltage clamp data on an isolated neurone soma. J Physiol. 1971 Feb;213(1):31–53. doi: 10.1113/jphysiol.1971.sp009366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Cottrell G. A. FMRFamide neuropeptides simultaneously increase and decrease K+ current in an identified neurone. Nature. 1982 Mar 4;296(5852):87–89. doi: 10.1038/296087a0. [DOI] [PubMed] [Google Scholar]
  17. Grafe P., Mayer C. J., Wood J. D. Synaptic modulation of calcium-dependent potassium conductance in myenteric neurones in the guinea-pig. J Physiol. 1980 Aug;305:235–248. doi: 10.1113/jphysiol.1980.sp013360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gustafsson B., Wigström H. Evidence for two types of afterhyperpolarization in CA1 pyramidal cells in the hippocampus. Brain Res. 1981 Feb 16;206(2):462–468. doi: 10.1016/0006-8993(81)90548-5. [DOI] [PubMed] [Google Scholar]
  19. Haas H. L., Konnerth A. Histamine and noradrenaline decrease calcium-activated potassium conductance in hippocampal pyramidal cells. 1983 Mar 31-Apr 6Nature. 302(5907):432–434. doi: 10.1038/302432a0. [DOI] [PubMed] [Google Scholar]
  20. Hablitz J. J. Altered burst responses in hippocampal CA3 neurons injected with EGTA. Exp Brain Res. 1981;42(3-4):483–485. doi: 10.1007/BF00237513. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Horn J. P., McAfee D. A. Alpha-drenergic inhibition of calcium-dependent potentials in rat sympathetic neurones. J Physiol. 1980 Apr;301:191–204. doi: 10.1113/jphysiol.1980.sp013198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Krnjević K., Puil E., Werman R. EGTA and motoneuronal after-potentials. J Physiol. 1978 Feb;275:199–223. doi: 10.1113/jphysiol.1978.sp012186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lewis D. V., Wilson W. A. Calcium influx and poststimulus current during early adaptation in Aplysia giant neurons. J Neurophysiol. 1982 Jul;48(1):202–216. doi: 10.1152/jn.1982.48.1.202. [DOI] [PubMed] [Google Scholar]
  26. Madison D. V., Nicoll R. A. Noradrenaline blocks accommodation of pyramidal cell discharge in the hippocampus. Nature. 1982 Oct 14;299(5884):636–638. doi: 10.1038/299636a0. [DOI] [PubMed] [Google Scholar]
  27. Meech R. W. Calcium-dependent potassium activation in nervous tissues. Annu Rev Biophys Bioeng. 1978;7:1–18. doi: 10.1146/annurev.bb.07.060178.000245. [DOI] [PubMed] [Google Scholar]
  28. Morita K., North R. A., Tokimasa T. Muscarinic agonists inactivate potassium conductance of guinea-pig myenteric neurones. J Physiol. 1982 Dec;333:125–139. doi: 10.1113/jphysiol.1982.sp014443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Newberry N. R., Nicoll R. A. A bicuculline-resistant inhibitory post-synaptic potential in rat hippocampal pyramidal cells in vitro. J Physiol. 1984 Mar;348:239–254. doi: 10.1113/jphysiol.1984.sp015107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Ottoson D., Swerup C. Studies on the role of calcium in adaptation of the crustacean stretch receptor. Effects of intracellular injection of calcium, EGTA and TEA. Brain Res. 1982 Jul 29;244(2):337–341. doi: 10.1016/0006-8993(82)90093-2. [DOI] [PubMed] [Google Scholar]
  32. Schwartzkroin P. A., Stafstrom C. E. Effects of EGTA on the calcium-activated afterhyperpolarization in hippocampal CA3 pyramidal cells. Science. 1980 Dec 5;210(4474):1125–1126. doi: 10.1126/science.6777871. [DOI] [PubMed] [Google Scholar]
  33. Schwindt P. C., Calvin W. H. Nature of conductances underlying rhythmic firing in cat spinal motoneurons. J Neurophysiol. 1973 Nov;36(6):955–973. doi: 10.1152/jn.1973.36.6.955. [DOI] [PubMed] [Google Scholar]
  34. Tosaka T., Tasaka J., Miyazaki T., Libet B. Hyperpolarization following activation of K+ channels by excitatory postsynaptic potentials. Nature. 1983 Sep 8;305(5930):148–150. doi: 10.1038/305148a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wood J. D., Mayer C. J. Serotonergic activation of tonic-type enteric neurons in guinea pig small bowel. J Neurophysiol. 1979 Mar;42(2):582–593. doi: 10.1152/jn.1979.42.2.582. [DOI] [PubMed] [Google Scholar]

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

RESOURCES