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

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Summary

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.

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References

  • Alger BE, Nicoll RA (1980) Epileptiform burst after hyperpolarization: calcium-dependent potassium potential in hippocampal CA1 pyramidal cells. Science 210: 1122–1124

    Google Scholar 

  • Alger BE, Nicoll RA (1982) Feed forward dendritic inhibition in rat hippocampal pyramidal cells studied in vitro. J Physiol (Lond) 328: 105–123

    Google Scholar 

  • Andersen P, Bliss TVP, Skrede KK (1971) Unit analysis of hippocampal population spikes. Exp Brain Res 13: 208–221

    Google Scholar 

  • Andersen P, Eccles JC, Loyning Y (1964a) Location of postsynaptic inhibitory synapses on hippocampal pyramids. J Neurophysiol 27: 592–607

    Google Scholar 

  • Andersen P, Eccles JC, Loyning Y (1964b) Pathway of postsynaptic inhibition in the hippocampus. J Neurophysiol 27: 608–619

    Google Scholar 

  • 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: 59P

  • 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: 279–292

    Google Scholar 

  • Ashwood TJ, Wheal HV (1985) GABA responses in CA1 pyramidal neurones in slices of the kainic acid (KA) lesioned rat hippocampus. J Physiol 358: 21P

  • 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: 515–528

    Google Scholar 

  • 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: 1361–1391

    Article  CAS  PubMed  Google Scholar 

  • Bragdon AC, Wilson WA (1982) CA1 pyramidal cells exhibit spike frequency adaptation and a slow outward current. Neuroscience Abstr 8: 1015

    Google Scholar 

  • Brown DA, Griffith WH (1983) Persistent slow inward calcium current in voltage-clamped hippocampal neurones of the guinea-pig. J Physiol (Lond) 337: 303–320

    Google Scholar 

  • 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: 581–589

    Google Scholar 

  • Corsellis JAN, Meldrum BS (1976) Epilepsy. In: Blackwood W, Corsellis JAN, (eds) Greenfields neuropathology, Edward Arnold

  • Curtis DR, Duggan AW, Felix D, Johnston GAR, McLennan H (1971) Antagonism between bicuculline and GABA in the cat brain. Brain Res 33: 57–73

    Google Scholar 

  • 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: 543

    Google Scholar 

  • Dichter M, Spencer WA (1969) Penicillin-induced interictal discharges from the cat hippocampus. II. Mechanisms underlying origin and restriction. J Neurophysiol 32: 663–687

    Google Scholar 

  • Dingledine R, Gjerstad L (1979) Penicillin blocks hippocampal IPSP's, unmasking prolonged EPSP's. Brain Res 168: 205–209

    Google Scholar 

  • Dingledine R, Langmoen IA (1980) Conductance changes and inhibitory actions of hippocampal recurrent IPSPs. Brain Res 185: 277–287

    Google Scholar 

  • Fisher RS, Alger BF (1984) Electrophysiological mechanisms of kainic acid induced epileptiform activity in the rat hippocampal slice. J Neurosci 4: 1312–1323

    Google Scholar 

  • Fonnum F, Walaas I (1978) The effect of intrahippocampal kainic acid injections and surgical lesions on neurotransmitters in hippocampus and septum. J Neurochem 31: 1173–1181

    Google Scholar 

  • Franck JE, Schwartzkroin PA (1985) Do kainate-lesioned hippocampi become epileptogenic? Brain Res 329: 309–313

    Google Scholar 

  • Halliwell JV, Adams PR (1982) Voltage-clamp analysis of muscarinic excitation in hippocampal neurones. Brain Res 250: 71–92

    Google Scholar 

  • Hotson JR, Prince DA (1980) A calcium-activated hyperpolarisation follows repetitive firing in hippocampal neurons. J Neurophysiol 43(2): 409–419

    Google Scholar 

  • Hotson JR, Prince DA, Schwartzkroin PA (1979) Anomalous inward rectification in hippocampal neurones. J Neurophysiol 42: 889–895

    Google Scholar 

  • Johnston D, Brown TH (1981) Giant synaptic potential hypothesis for epileptiform activity. Science 211: 294–297

    Google Scholar 

  • Johnston D, Hablitz JJ, Wilson WA (1980) Voltage clamp discloses slow inward current in hippocampal burst-firing neurones. Nature (Lond) 286: 391–393

    Google Scholar 

  • Kandel ER, Spencer WA, Brinley FJ (1961) Electrophysiology of hippocampal neurons. 1. Sequential invasion and synaptic organization. J Neurophysiol 24: 225–242

    Google Scholar 

  • Kehl SJ, McLennan H, Collingridge GL (1984) Effects of folic and kainic acids on synaptic responses of hippocampal neurones. Neuroscience 11: 111–124

    Google Scholar 

  • 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 99–111

    Google Scholar 

  • Lancaster B, Wheal HV (1982) A comparative histological and electrophysiological study of some neurotoxins in the rat hippocampus. J Comp Neurol 211: 105–114

    Google Scholar 

  • Lancaster B, Wheal HV (1983) Ca2+ dependence of afterhyperpolarizations (AHPs) in CA1 pyramidal cells of the rat. J Physiol (Lond) 334: 118–119P

    Google Scholar 

  • 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: 317–324

    Google Scholar 

  • 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: 431–443

    Google Scholar 

  • Lothman EW, Collins RC, (1981) Kainic acid induced limbic seizures: metabolic, behavioral, electroencephalographic and neuropathological correlates. Brain Res 218: 299–318

    Article  CAS  PubMed  Google Scholar 

  • Madison DV, Nicoll RA (1984) Control of the repetitive discharge of rat CA1 pyramidal neurones in vitro. J Physiol 354: 319–331

    Google Scholar 

  • 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: 499–530

    Google Scholar 

  • Nadler JV, Cuthbertson GJ (1980) Kainic acid neurotoxicity toward hippocampal formation: dependence on specific excitatory pathways. Brain Res 195: 47–56

    Google Scholar 

  • 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: 405–410

    Google Scholar 

  • Nadler JV, Perry BW, Cotman CW (1978a) Intraventricular kainic acid preferentially destroys hippocampal pyramidal cells. Nature (Lond) 271: 676–677

    Google Scholar 

  • 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 219–237

    Google Scholar 

  • Newberry NR, Nicoll RA (1984) A bicuculline-resistant inhibitory post-synaptic potential in rat hippocampal pyramidal cells in vitro. J Physiol (Lond) 348: 239–254

    Google Scholar 

  • Nicoll RA, Alger BE (1981) Synaptic activation may activate a calcium-dependent potassium conductance in hippocampal pyramidal cells. Science 212: 957–959

    Google Scholar 

  • Olney JW, Rhee VHoOL (1974) Kainic acid: a powerful neurotoxic analogue of glutamate. Brain Res 77: 507–512

    Google Scholar 

  • 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: 481–487

    Google Scholar 

  • Schwartzkroin PA, Prince DA (1980) Changes in excitatory and inhibitory synaptic potentials leading to epileptogenic activity. Brain Res 183: 61–76

    Google Scholar 

  • Schwindt PC, Crill WE (1984) The spinal cord model of experimental epilepsy. In: Schwarztkroin PA, Wheal HV (eds) Electrophysiology of epilepsy. Academic Press, London

    Google Scholar 

  • Wong RKS, Prince DA (1978) Participation of calcium spikes during intrinsic burst firing in hippocampal neurons. Brain Res 159: 385–390

    Google Scholar 

  • Wong RKS, Prince DA (1979) Dendritic mechanisms underlying penicillin-induced epileptiform activity. Science 204: 1228–1231

    Google Scholar 

  • Wong RKS, Prince DA, Basbaum AI (1979) Intradendritic recording from hippocampal neurons. Proc Natl Acad Sci USA 76: 986–990

    Google Scholar 

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Ashwood, T.J., Lancaster, B. & Wheal, H.V. Intracellular electrophysiology of CA1 pyramidal neurones in slices of the kainic acid lesioned hippocampus of the rat. Exp Brain Res 62, 189–198 (1986). https://doi.org/10.1007/BF00237415

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  • DOI: https://doi.org/10.1007/BF00237415

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