Experimental Brain Research

, Volume 62, Issue 1, pp 189–198

Intracellular electrophysiology of CA1 pyramidal neurones in slices of the kainic acid lesioned hippocampus of the rat

  • T. J. Ashwood
  • B. Lancaster
  • H. V. Wheal


Intracellular recordings were made from hippocampal CA1 pyramidal cells in slices where the CA3/CA4 region had been lesioned using intracerebroventricular kainic acid. In 55% of the cells studied orthodromic excitation evoked bursts of action potentials. This bursting activity was associated with a decrease in or loss of the early phase to the hyperpolarisation which normally follows orthodromically evoked action potentials. The recurrent inhibitory post-synaptic potential produced by antidromic activation of pyramidal cells was also reduced or absent. A late phase to the orthodromic hyperpolarisation was reduced in cells from lesioned slices. However, in normal slices treated with bicuculline this potential showed an apparent increase. The afterhyperpolarisation which follows a short current evoked burst of action potentials was reduced in bursting cells from lesioned slices. In addition, a silent period in the firing pattern produced by long depolarising current pulses was reduced or absent in these cells. These results together with observations made with bicuculline suggest that the bursting activity in lesioned slices is largely due to a loss of inhibition mediated by γ-aminobutyric acid. It is proposed that the kainic acid-lesioned in vitro hippocampus may be a suitable preparation for studying the electrophysiology of temporal lobe epilepsy.

Key words

Hippocampus Kainic acid Inhibition Epilepsy GABA 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alger BE, Nicoll RA (1980) Epileptiform burst after hyperpolarization: calcium-dependent potassium potential in hippocampal CA1 pyramidal cells. Science 210: 1122–1124Google Scholar
  2. Alger BE, Nicoll RA (1982) Feed forward dendritic inhibition in rat hippocampal pyramidal cells studied in vitro. J Physiol (Lond) 328: 105–123Google Scholar
  3. Andersen P, Bliss TVP, Skrede KK (1971) Unit analysis of hippocampal population spikes. Exp Brain Res 13: 208–221Google Scholar
  4. Andersen P, Eccles JC, Loyning Y (1964a) Location of postsynaptic inhibitory synapses on hippocampal pyramids. J Neurophysiol 27: 592–607Google Scholar
  5. Andersen P, Eccles JC, Loyning Y (1964b) Pathway of postsynaptic inhibition in the hippocampus. J Neurophysiol 27: 608–619Google Scholar
  6. Ashwood TJ, Lancaster B, Wheal HV (1983) Bursting activity in the kainic acid (KA) lesioned rat hippocampus is associated with a reduction in GABA-mediated inhibition. J Physiol (Lond) 336: 59PGoogle Scholar
  7. Ashwood TJ, Lancaster B, Wheal HV (1984) In vivo and in vitro studies on putative interneurones in the rat hippocampus: possible mediators of feed-forward inhibition. Brain Res 293: 279–292Google Scholar
  8. Ashwood TJ, Wheal HV (1985) GABA responses in CA1 pyramidal neurones in slices of the kainic acid (KA) lesioned rat hippocampus. J Physiol 358: 21PGoogle Scholar
  9. Ben-Ari Y, Tremblay E, Ottersen OP (1980) Injections of kainic acid into the amygdaloid complex of the rat: an electrographic, clinical and histological study in relation to the pathology of epilepsy. Neuroscience 5: 515–528Google Scholar
  10. Ben-Ari Y, Tremblay E, Riche D, Ghilini G, Naquet R (1981) Electrographic, clinical and pathological alterations following systemic administration of kainic acid, bicuculline or pentetrazole: metabolic mapping using the deoxyglucose method with special reference to the pathology of epilepsy. Neuroscience 6: 1361–1391CrossRefPubMedGoogle Scholar
  11. Bragdon AC, Wilson WA (1982) CA1 pyramidal cells exhibit spike frequency adaptation and a slow outward current. Neuroscience Abstr 8: 1015Google Scholar
  12. Brown DA, Griffith WH (1983) Persistent slow inward calcium current in voltage-clamped hippocampal neurones of the guinea-pig. J Physiol (Lond) 337: 303–320Google Scholar
  13. Cavalheiro EA, Riche DA, Le Gal La Salle G (1982) Long-term effects of intrahippocampal kainic acid injection in rats: a method for inducing spontaneous recurrent seizures. Electroenceph Clin Neurophysiol 53: 581–589Google Scholar
  14. Corsellis JAN, Meldrum BS (1976) Epilepsy. In: Blackwood W, Corsellis JAN, (eds) Greenfields neuropathology, Edward ArnoldGoogle Scholar
  15. Curtis DR, Duggan AW, Felix D, Johnston GAR, McLennan H (1971) Antagonism between bicuculline and GABA in the cat brain. Brain Res 33: 57–73Google Scholar
  16. Davies SW, Ashwood TJ, Wheal HV, Köhler C (1985) Glutamate decarboxylase (GAD) and GAD immunoreactivity (GADI) in the CA1 region of the kainic acid lesioned rat hippocampus. Neuroscience Lett Suppl 21: 543Google Scholar
  17. Dichter M, Spencer WA (1969) Penicillin-induced interictal discharges from the cat hippocampus. II. Mechanisms underlying origin and restriction. J Neurophysiol 32: 663–687Google Scholar
  18. Dingledine R, Gjerstad L (1979) Penicillin blocks hippocampal IPSP's, unmasking prolonged EPSP's. Brain Res 168: 205–209Google Scholar
  19. Dingledine R, Langmoen IA (1980) Conductance changes and inhibitory actions of hippocampal recurrent IPSPs. Brain Res 185: 277–287Google Scholar
  20. Fisher RS, Alger BF (1984) Electrophysiological mechanisms of kainic acid induced epileptiform activity in the rat hippocampal slice. J Neurosci 4: 1312–1323Google Scholar
  21. Fonnum F, Walaas I (1978) The effect of intrahippocampal kainic acid injections and surgical lesions on neurotransmitters in hippocampus and septum. J Neurochem 31: 1173–1181Google Scholar
  22. Franck JE, Schwartzkroin PA (1985) Do kainate-lesioned hippocampi become epileptogenic? Brain Res 329: 309–313Google Scholar
  23. Halliwell JV, Adams PR (1982) Voltage-clamp analysis of muscarinic excitation in hippocampal neurones. Brain Res 250: 71–92Google Scholar
  24. Hotson JR, Prince DA (1980) A calcium-activated hyperpolarisation follows repetitive firing in hippocampal neurons. J Neurophysiol 43(2): 409–419Google Scholar
  25. Hotson JR, Prince DA, Schwartzkroin PA (1979) Anomalous inward rectification in hippocampal neurones. J Neurophysiol 42: 889–895Google Scholar
  26. Johnston D, Brown TH (1981) Giant synaptic potential hypothesis for epileptiform activity. Science 211: 294–297Google Scholar
  27. Johnston D, Hablitz JJ, Wilson WA (1980) Voltage clamp discloses slow inward current in hippocampal burst-firing neurones. Nature (Lond) 286: 391–393Google Scholar
  28. Kandel ER, Spencer WA, Brinley FJ (1961) Electrophysiology of hippocampal neurons. 1. Sequential invasion and synaptic organization. J Neurophysiol 24: 225–242Google Scholar
  29. Kehl SJ, McLennan H, Collingridge GL (1984) Effects of folic and kainic acids on synaptic responses of hippocampal neurones. Neuroscience 11: 111–124Google Scholar
  30. Köhler C (1983) Neuronal degeneration after intracerebral injections of excitotoxins: a histological analysis of kainic acid, ibotenic acid and quinolinic acid lesions in the rat. In: Fuxe K, Roberts P, Schwarcz R, (eds) Excitotoxins. Macmillan Press, London pp 99–111Google Scholar
  31. Lancaster B, Wheal HV (1982) A comparative histological and electrophysiological study of some neurotoxins in the rat hippocampus. J Comp Neurol 211: 105–114Google Scholar
  32. Lancaster B, Wheal HV (1983) Ca2+ dependence of afterhyperpolarizations (AHPs) in CA1 pyramidal cells of the rat. J Physiol (Lond) 334: 118–119PGoogle Scholar
  33. Lancaster B, Wheal HV (1984) Chronic failure of inhibition in the CA1 area of the hippocampus following kainic acid lesions of the CA3/4 area. Brain Res 295: 317–324Google Scholar
  34. Lanthorn T, Storm J, Andersen P (1984) Current-to-frequency transduction in CA1 hippocampal pyramidal cells: slow prepotentials dominate the primary range firing. Exp Brain Res 53: 431–443Google Scholar
  35. Lothman EW, Collins RC, (1981) Kainic acid induced limbic seizures: metabolic, behavioral, electroencephalographic and neuropathological correlates. Brain Res 218: 299–318CrossRefPubMedGoogle Scholar
  36. Madison DV, Nicoll RA (1984) Control of the repetitive discharge of rat CA1 pyramidal neurones in vitro. J Physiol 354: 319–331Google Scholar
  37. Margerison JH, Corsellis JAN (1966) Epilepsy and the temporal lobes: a clinical, electroencephalographic and neuropathological study of the brain in epilepsy, with particular reference to the temporal lobes. Brain 89: 499–530Google Scholar
  38. Nadler JV, Cuthbertson GJ (1980) Kainic acid neurotoxicity toward hippocampal formation: dependence on specific excitatory pathways. Brain Res 195: 47–56Google Scholar
  39. Nadler JV, Evenson DA, Smith EM (1981) Evidence from lesion studies for epileptogenic and non-epileptogenic neurotoxic interactions between kainic acid and excitatory innervation. Brain Res 205: 405–410Google Scholar
  40. Nadler JV, Perry BW, Cotman CW (1978a) Intraventricular kainic acid preferentially destroys hippocampal pyramidal cells. Nature (Lond) 271: 676–677Google Scholar
  41. Nadler JV, Perry BW, Cotman CW (1978b) Preferential vulnerability of hippocampus to intraventricular kainic acid. In: McGeer EG, Olney JW, McGeer PL, (eds) Kainic acid as a tool in neurobiology. Raven Press, New York, pp 219–237Google Scholar
  42. Newberry NR, Nicoll RA (1984) A bicuculline-resistant inhibitory post-synaptic potential in rat hippocampal pyramidal cells in vitro. J Physiol (Lond) 348: 239–254Google Scholar
  43. Nicoll RA, Alger BE (1981) Synaptic activation may activate a calcium-dependent potassium conductance in hippocampal pyramidal cells. Science 212: 957–959Google Scholar
  44. Olney JW, Rhee VHoOL (1974) Kainic acid: a powerful neurotoxic analogue of glutamate. Brain Res 77: 507–512Google Scholar
  45. Pisa M, Sandberg PR, Corcoran ME, Fibiger HC (1980) Spontaneous recurrent seizures after intracerebral injections of kainic acid in rat: a possible model of human temporal lobe epilepsy. Brain Res 200: 481–487Google Scholar
  46. Schwartzkroin PA, Prince DA (1980) Changes in excitatory and inhibitory synaptic potentials leading to epileptogenic activity. Brain Res 183: 61–76Google Scholar
  47. Schwindt PC, Crill WE (1984) The spinal cord model of experimental epilepsy. In: Schwarztkroin PA, Wheal HV (eds) Electrophysiology of epilepsy. Academic Press, LondonGoogle Scholar
  48. Wong RKS, Prince DA (1978) Participation of calcium spikes during intrinsic burst firing in hippocampal neurons. Brain Res 159: 385–390Google Scholar
  49. Wong RKS, Prince DA (1979) Dendritic mechanisms underlying penicillin-induced epileptiform activity. Science 204: 1228–1231Google Scholar
  50. Wong RKS, Prince DA, Basbaum AI (1979) Intradendritic recording from hippocampal neurons. Proc Natl Acad Sci USA 76: 986–990Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • T. J. Ashwood
    • 1
  • B. Lancaster
    • 1
  • H. V. Wheal
    • 1
  1. 1.Department of NeurophysiologyUniversity of Southampton, Bassett Crescent EastSouthamptonUK
  2. 2.Department of PharmacologyUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations