Skip to main content
Log in

Effects of GABA and bicuculline on N-methyl-D-aspartate- and quisqualate-induced reductions in extracellular free calcium in area CA1 of the hippocampal slice

  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Summary

Decreases in extracellular free calcium ([Ca2+]o) and concomitant field potentials were recorded from the dendritic and cell body layers of the CA1 field in transverse hippocampal slices. They were elicited by tetanic stimulation of Schaffer collaterals and commissural fibers or by iontophoretic application of the excitatory amino acids N-methyl-D-aspartate (NMDA) and quisqualate (Quis). Under control conditions, decreases in [Ca2+]o were found to be maximal in stratum pyramidale (SP). In stratum radiatum (SR), 100 μm away from SP, decreases in [Ca2+]o were half the size of those observed in SP. Bicuculline methiodide, bath-applied at concentrations of 10–100 μM, enhanced the reductions in [Ca2+]o, increased the field potentials in all layers and also induced “spontaneous” epileptiform activity. In the presence of bicuculline, the decreases in [Ca2+]o were particularly enhanced in SR and were often greater than those recorded in SP. This was the case for changes in [Ca2+]o induced either by repetitive electrical stimulation or by application of NMDA and Quis. When synaptic transmission was blocked by perfusing the slices with a low Ca2+ medium, all NMDA and Quis-induced changes in [Ca2+]o were predictably reduced but there was a relative enhancement of changes in [Ca2+]o in SR with respect to those in SP. We propose that, under normal conditions, an inhibitory control mediated by GABA limits the reductions of [Ca2+]o particularly in SR. In support of this proposal, we found that bath-applied GABA had a depressant action on changes in [Ca2+]o.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Alger BE, Nicoll RA (1979) GABA-mediated biphasic inhibitory responses in hippocampus. Nature 281: 315–317

    Google Scholar 

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

  • Alger BE, Nicoll RA (1982) Pharmacological evidence for two kinds of GABA receptor on rat hippocampal pyramidal cells studied in vitro. J Physiol (Lond) 328: 125–141

    Google Scholar 

  • Andersen P, Dingledine R, Gjerstad L, Langmoen IA, MosfeldtLaursen A (1980) Two different responses of hippocampal cells to application of gamma-aminobutyric acid. J Physiol (Lond) 305: 279–296

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • Barber R, Saito K (1976) Light microscopic visualization of GAD and GABA-T in immunocytochemical preparations of rodent CNS. In: Roberts E, Chase TN, Tower DB (eds) GABA in nervous system function. Raven Press, New York, pp 113–132

    Google Scholar 

  • Benninger C, Kadis J, Prince DA (1980) Extracellular calcium and potassium changes in hippocampal slices. Brain Res 187: 165–182

    Google Scholar 

  • Curtis DR, Felix D, McLennan H (1970) GABA and hippocampal inhibition. Br J Pharmacol 40: 881–883

    Google Scholar 

  • Deisz RA, Lux HD (1985) Gamma-aminobutyric acid-induced depression of calcium currents of chick sensory neurons. Neurosci Lett 56: 205–210

    Google Scholar 

  • Dietzel I, Heinemann U, Hofmeier G, Lux HD (1980) Transient changes in the size of extracellular space in the sensorimotor cortex of cats in relation to stimulus-induced changes in potassium concentration. Exp Brain Res 40: 432–439

    Google Scholar 

  • Dingledine R (1983) N-methyl aspartate activates voltage dependent calcium conductance in rat hippocampal pyramidal cells. J Physiol (Lond) 343: 385–405

    Google Scholar 

  • Dunlap K, Fischbach GD (1978) Neurotransmitters decrease the calcium component of sensory neurone action potentials. Nature 276: 837–839

    Google Scholar 

  • Dunlap K, Fischbach GD (1981) Neurotransmitter decrease the calcium conductance activated by depolarization of embryonic chick sensory neurones. J Physiol (Lond) 317: 519–535

    Google Scholar 

  • Fujita Y (1979) Evidence for the existence of inhibitory postsynaptic potentials in dendrites and their functional significance in hippocampal pyramidal cells of acult rabbits. Brain Res 175: 59–69

    Google Scholar 

  • Fujita Y, Sakata H (1962) Electrophysiological properties of CA1 and CA2 apical dendrites of rabbit hippocampus. J Neurophysiol 25: 209–222

    Google Scholar 

  • Galvan M, Adams PR (1982) Control of calcium current in rat sympathetic neurones by norepinephrine. Brain Res 244: 135–144

    Google Scholar 

  • Hablitz JJ (1982) Conductance changes induced by DL-homocysteic acid and N-methyl-DL-aspartic acid in hippocampal neurons. Brain Res 247: 149–153

    Google Scholar 

  • Hablitz JJ (1984) Picrotoxin-induced epileptiform activity in hippocampus: role of endogenous versus synaptic factors. J Neurophysiol 51: 1011–1027

    Google Scholar 

  • Heinemann U, Hamon B, Konnerth A (1984) GABA and baclofen reduce changes in extracellular free calcium in area CA1 of rat hippocampal slices. Neurosci Lett 47: 295–300

    Google Scholar 

  • Heinemann U, Konnerth A, Louvel J, Lux HD, Pumain R (1982) Changes in extracellular free Ca2+ in normal and epileptic sensorimotor cortex of cats. In: Klee MR, Lux HD, Speckmann EJ (eds) Physiology and pharmacology of epileptogenic phenomena. Raven Press, New York, pp 299–308

    Google Scholar 

  • Heinemann U, Konnerth A, Lux HD (1981) Stimulation induced changes in extracellular free calcium in normal cortex and chronic alumina cream foci of cats. Brain Res 213: 246–250

    Google Scholar 

  • Heinemann U, Neuhaus S, Dietzel I (1983) Aspects of potassium regulation in normal and gliotic brain tissue. In: BaldyMouliner M, Ingvar DH, Meldrum BS (eds) Cerebral blood flow, metabolism and epilepsy. John Libbey and Co, London Paris, pp 271–278

    Google Scholar 

  • Heinemann U, Lux HD, Gutnick MJ (1977) Extracellular free calcium and potassium during paroxysmal activity in cerebral cortex of the cat. Exp Brain Res 27: 237–243

    Google Scholar 

  • Heinemann U, Pumain R (1980) Extracellular calcium activity changes in cat sensorimotor cortex induced by iontophoretic application of excitatory amino acids. Exp Brain Res 40: 247–250

    Google Scholar 

  • Heyer EJ, Nowak LM, Macdonald RL (1981) Bicuculline: a convulsant with synaptic and nonsynaptic actions. Neurology 31: 1381–1390

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • Iversen LL and Johnston GAR (1970) GABA uptake in rat central nervous system: comparison of uptake in slices and homogenates and the effects of some inhibitors. J Neurochem 18: 1939–1950

    Google Scholar 

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

    Google Scholar 

  • Klee MR, Misgeld U, Zeise ML (1981) Pharmacological differences between CA3 and dentate granule cells in hippocampal slices. In: Feher O, Joo F (eds) Cellular analogues of conditioning and neural plasticity. Adv Physiol Sci Vol 36. Akademiai Kiado, Budapest and Pergamon Press, Budapest, pp 145–154

    Google Scholar 

  • Konnerth A, Heinemann U (1983a) Effects of GABA on presumed presynaptic Ca2+ entry in hippocampal slices. Brain Res 270: 185–189

    Google Scholar 

  • Krnjevic K, Morris ME, Reiffenstein RJ (1980) Changes in extracellular Ca2+ and K+ activity accompanying hippocampal discharges. Can J Physiol Pharmacol 58: 579–583

    Google Scholar 

  • Krnjevic K, Morris ME, Reiffenstein RJ, Ropert N (1982) Depth distribution and mechanism of changes in extracellular K+ and Ca2+ concentrations in the hippocampus. Can J Physiol Pharmacol 60: 1658–1671

    Google Scholar 

  • Lambert JDC, Flatman JA, Engberg I (1981) In: di Chiara G, Gessa GL (eds) Glutamate as a neurotransmitter. Raven Press, New York, pp 205–216

    Google Scholar 

  • Lambert JDC, Heinemann U (1986) Aspects of the action excitatory of amino acids on hippocampal CA 1 neurones. In: Heinemann U, Klee MR, Neher E, Singer W (eds) Calcium electrogenesis and neuronal functioning. Exp Brain Res Suppl (in press)

  • Loeffler JP, Desaulles E, Demeneix BA, Feltz P (1982) Electrophysiological study with K+-and Ca2+-sensitive micropipettes of GABA receptors in the rat neurointermediate lobe in vitro. Neurosci Lett 34: 271–274

    Google Scholar 

  • Louvel J, Heinemann U (1981) Mode d'action du pentetrazole au niveau cellulaire. Rev EEG Neurophysiol (Paris) 11: 335–339

    Google Scholar 

  • Lux HD (1971) Ammonium and chloride extrusion: hyperpolarizing synaptic inhibition in spinal motoneurons. Science 173: 555–557

    Google Scholar 

  • Marciani MG, Louvel J, Heinemann U (1982) Aspartate-induced changes in extracellular free calcium in ‘in vitro’ hippocampal slices of rats. Brain Res 238: 272–277

    Google Scholar 

  • Martin DL (1976) Carrier mediated transport and removal of GABA from synaptic regions. In: Roberts E, Chase TN, Tower TB (eds) GABA in nervous system function. Raven Press New York: 347–386

    Google Scholar 

  • Newberry NR, Nicoll RA (1985) Comparison of the action of baclofen with-aminobutyric acid on rat hippocampal pyramidal cells in vitro. J Physiol (Lond) 360: 161–185

    Google Scholar 

  • Nicholson C, Phillips JM (1981) Ion diffusion modified by tortuosity and volume fraction in the extracellular microenvironment of rat cerebellum. J Physiol (Lond) 321: 225–257

    Google Scholar 

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

    Google Scholar 

  • Nowak L, Bregestovski P, Ascher P, Herbet A, Prochiantz A (1984) Magnesium gates glutamate-activated channels in mouse central neurons. Nature 307: 462–465

    Google Scholar 

  • Pellmar TC, Carpenter DO (1980) Serotonin induces a voltage-sensitive calcium current in neurons of Aplysia californica. J Neurophysiol 44: 423–439

    Google Scholar 

  • Pumain R, Heinemann U (1985) Stimulus-evoked and amino acid-induced calcium and potassium changes in rat neocortex. J Neurophysiol 53: 1–16

    Google Scholar 

  • Ribak CE, Vaughn JE, Saito K (1978) Immunocytochemical localization of glutamic acid decarboxylase in neuronal somata following colchicine inhibition of axonal transport. Brain Res 140: 315–332

    Google Scholar 

  • Schlichter R, Demeneix BA, Desarmenien M, Desaulles E, Loeffler JP, Feltz P (1984) Properties of the GABA receptors located on spinal primary afferent neurones and hypophyseal neuroendocrine cells of the rat. Neurosci Lett 47: 257–263

    Google Scholar 

  • Schwartzkroin PA, Prince DA (1978) Cellular and field potential properties of epileptogenic hippocampal slices. Brain Res 147: 117–130

    Google Scholar 

  • Schwartzkroin PA, Slawsky M (1977) Probable calcium spikes in hippocampal neurons. Brain Res 135–161

  • Somogyi P, Smith AD, Nunzi MG, Gorio A, Tagaki H, Bu JY (1983) Glutamate decarboxylase immunoreactivity in the hippocampus of the cat: distribution of immunoreactive synaptic terminals with special reference to the axon initial segment of pyramidal neurons. J Neurosci 3: 1450

    Google Scholar 

  • Storm-Mathisen J (1977) Localization of transmitter candidates in the brain: the hippocampal formation as a model. Progr Neurobiol 8: 119–181

    Google Scholar 

  • Wadman WJ, Heinemann U, Konnerth A, Neuhaus S (1985): Hippocampal slices of kindled rats reveal calcium involvement in epileptogenesis. Exp Brain Res 57: 404–407

    Google Scholar 

  • Watkins JC (1984) Excitatory amino acids and central synaptic transmission. Trends Pharmacol Sci 5: 373–375

    Google Scholar 

  • Wheal HV, Ashwood TJ, Lancaster B (1984) A comparative in vitro study of the kainic acid lesioned and bicuculline treated hippocampus chronic and acute models of focal epilepsy. In: Schwartzkroin PA, Wheal HV (eds) Electrophysiology of epilepsy. Academic Press, London, pp 177–199

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • Zanotto L, Heinemann U (1983) Aspartate and glutamate-induced reductions in extracellular free calcium and sodium concentration in area CA1 of ‘in vitro’ hippocampal slices of rats. Neurosci Lett 35: 79–84

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by SFB 220/B3 and He 1128/3-2 from the Deutsche Forschungsgemeinschaft

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hamon, B., Heinemann, U. Effects of GABA and bicuculline on N-methyl-D-aspartate- and quisqualate-induced reductions in extracellular free calcium in area CA1 of the hippocampal slice. Exp Brain Res 64, 27–36 (1986). https://doi.org/10.1007/BF00238198

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00238198

Key words

Navigation