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Hyperpolarizing potentials in guinea pig hippocampal CA3 neurons

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Summary

  1. 1.

    There is a bewildering variety of hyperpolarizing potentials which control activity in hippocampal pyramidal cells. These include an inhibitory postsynaptic potential (IPSP) with early and late components, voltage- and calcium-dependent potassium conductances, a voltage-dependent potassium conductance modulated by muscarinic agents (the M-current), and a complex and poorly understood afterhyper-polarization following epileptiform bursts.

  2. 2.

    In hippocampal CA3 pyramidal cells, mossy fiber stimulation elicits an IPSP which is made up of two readily separable components. Using thein vitro slice preparation, we investigated the underlying ionic basis of these IPSP components and compared them to other hyperpolarizing potentials characteristic of the CA3 neurons.

  3. 3.

    Intracellular recordings were obtained and then tissue was exposed to bathing medium low in chloride concentration or high in potassium concentration; the ion “blockers” EGTA (intracellular); tetraethylammonium (TEA) (intra- and extracellular), and barium and cobalt (extracellular); and the γ-aminobutyric acid (GABA)/ chloride antagonists penicillin, bicuculline and picrotoxin.

  4. 4.

    As has been reported by others, the early part of the CA3 IPSP is a GABAergic, chloride-dependent potential generated at proximal (probably somatic) membrane. The later component of the IPSP is a potassium-dependent synaptic potential, which is picrotoxin and bicuculline insensitive, not dependent on increases in intracellular calcium, and apparently produced on distal (dendritic) membranes.

  5. 5.

    The later component of the IPSP is clearly different from the calcium-dependent potassium conductance [g K(Ca)] responsible for hyperpolarizations following normal spontaneous and current-induced burst discharge in hippocampal pyramidal cells. The late component of the IPSP may have some similarities to the afterhyperpolarization seen following penicillin-induced burst discharges.

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References

  • Alger, B. E. (1984). Characteristics of a slow hyperpolarizing synaptic potential in rat hippocampal pyramidal cells.J. Neurophysiol. (in press).

  • Alger, B. E., and Nicoll, R. A. (1979). GABA-mediated biphasic inhibitory responses in hippocampus.Nature 281315–317.

    Google Scholar 

  • Alger, B. E., and Nicoll, R. A. (1980). Epileptiform burst afterhyperpolarization: Calcium-dependent potassium potential in hippocampal CA1 pyramidal cells.Science 2101122–1124.

    Google Scholar 

  • Alger, B. E., and Nicoll, R. A. (1982a). Feed-forward dendritic inhibition in rat hippocampal pyramidal cells studiedin vitro.J. Physiol. 328105–123.

    Google Scholar 

  • Alger, B. E., and Nicoll, R. A. (1982b). Pharmacological evidence for two kinds of GABA receptor on rat hippocampal pyramidal cells studiedin vitro.J. Physiol. 328125–141.

    Google Scholar 

  • Allen, G. I., Eccles, J. C., Nicoll, R. A., Oshima, T., and Rubia, F. J. (1977). The ionic mechanisms concerned in generating the IPSPs of hippocampal pyramidal cells.Proc. R. Soc. Lond. B 198363–384.

    Google Scholar 

  • Andersen, P., Eccles, J. C., and Loyning, Y. (1964a). Location of postsynaptic inhibitory synapses on hippocampal pyramids.J. Neurophysiol. 27592–607.

    Google Scholar 

  • Andersen, P., Eccles, J. C., and Loyning, Y. (1964b). Pathway of postsynaptic inhibition in the hippocampus.J. Neurophysiol. 27608–619.

    Google Scholar 

  • Andersen, P., Dingledine, R., Gjerstad, L., Langmoen, I. A., and Mosfeldt Laursen, A. (1980). Two different responses of hippocampal pyramidal cells to application of GABA.J. Physiol. 305279–296.

    Google Scholar 

  • Ault, B., and Nadler, J. V. (1982). Baclofen selectively inhibits transmission at synapses made by axons of CA3 pyramidal cells in the hippocampal slice.J. Pharmacol. Exp. Ther. 223291–297.

    Google Scholar 

  • Ault, B., and Nadler, J. V. (1983). Anticonvulsant-like actions of baclofen in the rat hippocampal slice.Br. J. Pharmacol. 78701–708.

    Google Scholar 

  • Benardo, L. S., and Prince, D. A. (1982). Dopamine action on hippocampal pyramidal cells.J. Neurosci. 2415–423.

    Google Scholar 

  • Biscoe, T. J., and Straughan, D. W. (1966). Micro-electrophoretic studies of neurons in the cat hippocampus.J. Physiol. 183341–359.

    Google Scholar 

  • Brown, D. A., and Griffith, W. H. (1983). Calcium-activated outward current in voltage-clamped hippocampal neurons of the guinea-pig.J. Physiol. 337 287–301.

    Google Scholar 

  • Cain, C. R., and Simmonds, M. A. (1982). Effects of baclofen on the olfactory cortex slice preparation.Neuropharmacology 21371–373.

    Google Scholar 

  • Curtis, D. R., Felix, D., and McLennan, H. (1970). GABA and hippocampal inhibition.Br. J. Pharmacol. 40881–883.

    Google Scholar 

  • Curtis, D. R., Duggan, A. W., Felix, D., Johnston, G. A. R., and McLennan, H. (1971). Antagonism between bicuculline and GABA in the cat.Brain Res. 3357–73.

    Google Scholar 

  • Dingledine, R., and Gjerstad, L. (1980a). Reduced inhibition during epileptiform activity in thein vitro hippocampal slice.J. Physiol. 305297–313.

    Google Scholar 

  • Dingledine, R., and Langmoen, I. A. (1980b). Conductance changes and inhibitory actions of hippocampal recurrent IPSPs.Brain Res. 185277–287.

    Google Scholar 

  • Eccles, J. C., Nicoll, R. A., Oshima, T., and Rubia, F. J. (1977). The anionic permeability of the inhibitory postsynaptic membrane of hippocampal pyramidal cells.Proc. R. Soc. Lond. B 198345–361.

    Google Scholar 

  • Fujita, Y. (1979). Evidence for the existence of IPSPs in dendrites and their functional significance in hippocampal pyramidal cells of adult rabbits.Brain Res. 17559–69.

    Google Scholar 

  • Fung, S.- C., and Fillenz, M. (1983). The role of pre-synaptic GABA and benzodiazepine receptors in the control of noradrenaline release in rat hippocampus.Neurosci. Lett. 4261–66.

    Google Scholar 

  • Gustafsson, B., Galvan, M., Grafe, P., and Wigstrom, H. (1982). A transient outward current in a mammalian central neurone blocked by 4-aminopyridine.Nature 299252–254.

    Google Scholar 

  • Hablitz, J. J. (1981a). Altered burst responses in hippocampal CA3 neurons injected with EGTA.Exp. Brain Res. 42483–485.

    Google Scholar 

  • Hablitz, J. J. (1981b). Effects of intracellular injections of chloride and EGTA on postepileptiform-burst hyperpolarizations in hippocampal neurons.Neurosci. Lett. 22159–163.

    Google Scholar 

  • Halliwell, J. V., and Adams, P. R. (1982). Voltage-clamp analysis of muscarinic excitation in hippocampal neurons.Brain. Res. 25071–92.

    Google Scholar 

  • Hotson, J. R., and Prince, D. A. (1980). A calcium-activated hyperpolarization follows repetitive firing in hippocampal neurons.J. Neurophysiol. 43409–419.

    Google Scholar 

  • Hotson, J. R., and Prince, D. A. (1981). Penicillin- and barium-induced epileptiform bursting in hippocampal neurons: Actions on Ca++ and K+ potentials.Ann. Neurol. 1011–17.

    Google Scholar 

  • Kandel, E. R., and Spencer, W. A. (1961). Electrophysiology of hippocampal neurons. II. After-potentials and repetitive firing.J. Neurophysiol. 21243–259.

    Google Scholar 

  • Kandel, E. R., Spencer, W. A., and Brinley, F. J. (1961). Electrophysiology of hippocampal neurons. I. Sequential invasion and synaptic organization.J. Neurophysiol. 21225–242.

    Google Scholar 

  • Kehl, S. J., and McLennan, H. (1983). Evidence for a bicuculline-insensitive long-lasting inhibition in the CA3 region of the rat hippocampal slice.Brain Res. 279278–281.

    Google Scholar 

  • Madison, D. V., and Nicoll, R. A. (1983). Adaptation of action potential frequency in hippocampal pyramidal cells is regulated by calcium-activated potassium conductance and M-current.Neurosci. Abstr. 9601.

    Google Scholar 

  • Mesher, R. A., and Schwartzkroin, P. A. (1980). Can CA3 epileptiform discharge induce bursting in normal CA1 hippocampal neurons?Brain Res. 183472–476.

    Google Scholar 

  • Newberry, N. R., and Nicoll, R. A. (1982). Properties of the late hyperpolarizing potential in hippocampal cell in vitro.Neurosci. Abstr. 8412.

    Google Scholar 

  • Newberry, N. R., and Nicoll, R. A. (1983). Direct inhibitory action of baclofen on hippocampal pyramidal cells.Neurosci. Abstr. 9457.

    Google Scholar 

  • Nicoll, R. A., and Alger, B. E. (1981). Synaptic excitation may activate a calcium-dependent potassium conductance in hippocampal pyramidal cells.Science 212957–959.

    Google Scholar 

  • Ogata, N. (1975). Ionic mechanisms of the depolarizing shift in thin hippocampal slices.Exp. Neurol. 46147–155.

    Google Scholar 

  • Ogata, N. (1978). Possible explanations for interictal-ictal transition: Evolution of epileptiform activity in hippocampal slice by chloride depletion.Experientia 341035–1036.

    Google Scholar 

  • Prince, D. A. (1968). Inhibition in “epileptic” neurons.Exp. Neurol. 21307–321.

    Google Scholar 

  • Schwartzkroin, P. A. (1975). Characteristics of CA1 neurons recorded intracellularly in the hippocampal in vitro slice preparation.Brain Res. 85423–436.

    Google Scholar 

  • Schwartzkroin, P. A. (1981). To slice or not to slice. InElectrophysiology of Isolated Mammalian CNS Preparations (Kerkut, G. A., and Wheal, H. V., Eds.), Academic Press, New York, pp. 15–49.

    Google Scholar 

  • Schwartzkroin, P. A., and Haglund, M. M. (1982). Seizure generation in hippocampal slices from immature rabbit.Neurosci. Abstr. 81017.

    Google Scholar 

  • Schwartzkroin, P. A., and Mathers, L. H. (1978). Physiological and morphological identification of a nonpyramidal hippocampal cell type.Brain Res. 1571–10.

    Google Scholar 

  • Schwartzkroin, P. A., and Prince, D. A. (1980a). Effects of TEA on hippocampal neurons.Brain Res. 185169–181.

    Google Scholar 

  • Schwartzkroin, P. A., and Prince, D. A. (1980b). Changes in excitatory and inhibitory synaptic potentials leading to epileptogenic activity.Brain Res. 18361–76.

    Google Scholar 

  • Schwartzkroin, P. A., and Stafstrom, C. E. (1980c). Effects of EGTA on the calcium-activated afterhyper-polarization in hippocampal CA3 pyramidal cells.Science 2101125–1126.

    Google Scholar 

  • Schwartzkroin, P. A., and Wyler, A. R. (1980d). Mechanisms underlying epileptiform burst discharge.Ann. Neurol. 795–107.

    Google Scholar 

  • Segal, M. (1980). The action of serotonin in the rat hippocampal slice preparation.J. Physiol. 303423–439.

    Google Scholar 

  • Simmonds, M. A. (1983). Multiple GABA receptors and associated regulatory sites.Trends Neurosci. 6279–281.

    Google Scholar 

  • Thalmann, R. H. (1984). Reversal properties of an EGTA-resistant late hyperpolarization that follows synaptic stimulation of hippocampal neurons.Neurosci. Lett. 46103–108.

    Google Scholar 

  • Thalmann, R. H., and Ayala, G. F. (1982). A late increase in potassium conductance follows synaptic stimulation of granule neurons of the dentate gyrus.Neurosci. Lett. 9243–248.

    Google Scholar 

  • Thalmann, R. H., Peck, E. J., and Ayala, G. F. (1981). Biphasic response of hippocampal pyramidal neurons to GABA.Neurosci. Lett. 21319–324.

    Google Scholar 

  • Wilson, W. A., Zbicz, K. L., and Lewis, D. V. (1982). Enhancement of spike frequency adaptation by anticonvulsants. InPhysiology and Pharmacology of Epileptogenic Phenomena (Klee, M. R., Lux, H. D., and Speckmann, E.- J., Eds.), Raven Press, New York, pp. 259–269.

    Google Scholar 

  • Wong, R. K. S., and Traub, R. D. (1983). Synchronized burst discharge in the disinhibited hippocampal slice. I. Initiation in the CA2-CA3 region.J. Neurophysiol. 49442–458.

    Google Scholar 

  • Wong, R. K. S., and Watkins, D. J. (1982). Cellular factors influencing GABA response in hippocampal pyramidal cells.J. Neurophysiol. 48938–951.

    Google Scholar 

  • Yamamoto, C. (1972a). Activation of hippocampal neurons by mossy fiber stimulation in thin brain sectionsin vitro.Exp. Brain Res. 14423–435.

    Google Scholar 

  • Yamamoto, C. (1972b). Intracellular study of seizure-like afterdischarges elicited in thin hippocampal sectionsin vitro.Exp. Neurol. 35154–164.

    Google Scholar 

  • Yamamoto, C., and Kawai, N. (1968). Generation of the seizure discharge in thin sections from the guinea-pig brain in chloride-free mediumin vitro.Jap. J. Physiol. 18620–631.

    Google Scholar 

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Knowles, W.D., Schneiderman, J.H., Wheal, H.V. et al. Hyperpolarizing potentials in guinea pig hippocampal CA3 neurons. Cell Mol Neurobiol 4, 207–230 (1984). https://doi.org/10.1007/BF00733586

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  • DOI: https://doi.org/10.1007/BF00733586

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