Skip to main content
SpringerLink
Log in

Potentiation of a metabotropic glutamatergic response following NMDA receptor activation in rat hippocampus

  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

Interactions between metabotropic glutamate andN-methyl-D-aspartate (NMDA) receptor-mediated responses were investigated in hippocampal CA3 cells using the single-electrode voltage-clamp method. Bath application (2.5–10 μM, 30 s) or iontophoresis of 1-amino-cyclopentyl-trans-1S, 3R-dicarboxylate (ACPD), a selective agonist for metabotropic glutamate receptors, resulted in an inward current associated with a decrease in membrane conductance. Following transient bath application of NMDA (5–10 μM, 30–60 s), the ACPD-induced inward current was potentiated for a period of up to 25 min (by 61±8% with bath application, by 32±15% with iontophoresis). Transient application of NMDA did not result in a potentiation of ionotropic RS-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or metabotropic muscarinic responses. ACPD responses were not potentiated following transient AMPA application. Intracellular buffering of calcium with tetrapotassium bis(O-aminophenoxy)-ethane-N,N,N′,N′-tetraacetic acid (BAPTA) prevented potentiation by NMDA in all cells. Bath application of arachidonic acid did not mimic the NMDA-induced potentiation. These results demonstrate that activation of NMDA receptors can specifically induce a long-lasting potentiation of a metabotropic glutamatergic response in hippocampal CA3 pyramidal cells. The characterization of this interaction may contribute to the elucidation of the physiological significance of metabotropic glutamate receptors.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Aniksztejn L, Otani S, Ben-Ari Y (1992) Quisqualate metabotropic receptors modulate NMDA currents and facilitate induction of long-term potentiation through protein kinase C. Eur J Neurosci 4:500–505

    Google Scholar 

  2. Barrionuevo G, Brown TH (1983) Associative long-term potentiation in hippocampal slices. Proc Natl Acad Sci USA 80:7347–7351

    Google Scholar 

  3. Baude A, Nusser Z, Roberts JDB, Mulvihill E, McIlhinney RAJ, Somogyi P (1993) The metabotropic glutamate receptor (mGluR1α) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron 11:771–787

    Google Scholar 

  4. Bashir ZI, Bortolotto ZA, Davies CH, Berretta N, Irving AJ, Seal AJ, Henley JM, Jane DE, Watkins JC, Collingridge GL (1993) Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors. Nature 363: 347–350

    Google Scholar 

  5. Behnisch T, Reymann KG (1993) Co-activation of metabotropic glutamate and N-methyl-D-aspartate receptors is involved in mechanisms of long-term potentiation maintenance in rat hippocampal CA1 neurons. Neuroscience 54:37–47

    Google Scholar 

  6. Bleakman D, Rusin KI, Chard PS, Glaum SR, Miller RJ (1992) Metabotropic glutamate receptors potentiate ionotropic glutamate responses in the rat dorsal horn. Mol Pharmacol 42:192–196

    Google Scholar 

  7. Brown DA (1983) Slow cholinergic excitation — a mechanism for increasing neuronal excitability. Trends Neurosci 6:302–307

    Google Scholar 

  8. Brown DA, Gähwiler BH, Griffith WH, Halliwell JV (1990) Membrane currents in hippocampal neurons. Prog Brain Res 83:141–160

    Google Scholar 

  9. Charpak S, Gähwiler BH (1991) Glutamate mediates a slow synaptic response in hippocampal slice cultures. Proc R Soc Lond [Biol] 243:221–226

    Google Scholar 

  10. Charpak S, Gähwiler BH, Do KQ, Knöpfel T (1990) Potassium conductances in hippocampal neurons blocked by excitatory amino-acid transmitters. Nature 347:765–767

    Google Scholar 

  11. Chetkovich DM, Gray R, Johnston D, Sweatt JD (1991) N-methyl-D-aspartate receptor activation increases cAMP levels and voltage-gated Ca2+ channel activity in area CA1 of hippocampus. Proc Natl Acad Sci USA 88:6467–6471

    Google Scholar 

  12. Debanne D, Gähwiler BH, Thompson SM (1994) Asynchronous pre- and postsynaptic activity induces associative long-term depression in area CA1 of the rat hippocampus in vitro. Proc Natl Acad Sci USA (in press)

  13. Dumuis A, Sebben M, Haynes L, Pin JP, Bockaert J (1988) NMDA receptors activate the arachidonic acid cascade system in striatal neurons. Nature 336:68–70

    Google Scholar 

  14. Gähwiler BH (1981) Organotypic monolayer cultures of nervous tissue. J Neurosci Methods 4:329–342

    Google Scholar 

  15. Gerber U, Lüthi A, Gähwiler BH (1993) Inhibition of a slow synaptic response by a metabotropic glutamate receptor antagonist in hippocampal CA3 pyramidal cells. Proc R Soc Lond [Biol] 254:169–172

    Google Scholar 

  16. Guérineau NC, Gähwiler BH, Gerber U (1994) G-proteins mediate reduction of resting K+ current by metabotropic glutamate and muscarinic receptors in rat CA3 cells. J Physiol (Lond) 474:27–33

    Google Scholar 

  17. Harvey J, Collingridge GL (1993) Signal transduction pathways involved in the acute potentiation of NMDA responses by 1S,3R-ACPD in rat hippocampal slices. Br J Pharmacol 109:1085–1090

    Google Scholar 

  18. Irvine RF (1982) How is the level of free arachidonic acid controlled in mammalian cells? Biochem J 204:3–16

    Google Scholar 

  19. Irving AJ, Schofield JG, Watkins JC, Sunter DC, Collingridge GL (1990) 1S,3R-ACPD stimulates and L-AP3 blocks Ca2+ mobilization in rat cerebellar neurons. Eur J Pharmacol 186:363–365

    Google Scholar 

  20. Kelso SR, Nelson TE, Leonard JP (1992) Protein kinase C — mediated enhancement of NMDA currents by metabotropic glutamate receptors inXenopus oocytes. J Physiol (Lond) 449:705–718

    Google Scholar 

  21. Keyser DO, Alger BE (1990) Arachidonic acid modulates hippocampal calcium current via protein kinase C and oxygen radicals. Neuron 5:545–553

    Google Scholar 

  22. Kinney GA, Slater NT (1993) Potentiation of NMDA receptor-mediated transmission in turtle cerebellar granule cells by activation of metabotropic glutamate receptors. J Neurophysiol 69:585–594

    Google Scholar 

  23. Klann E, Chen SJ, Sweatt JD (1991) Persistent protein kinase activation in the maintenance phase of long-term potentiation. J Biol Chem 266:24253–24256

    Google Scholar 

  24. Lowenstein CJ, Snyder SH (1992) Nitric oxide, a novel biologic messenger. Cell 70:705–707

    Google Scholar 

  25. Lüthi A, Gähwiler BH, Gerber U (1993) Potentiation of the ACPD-induced inward current after NMDA receptor activation in rat hippocampus. Eur J Neurosci [Suppl] 6:186

    Google Scholar 

  26. Lynch MA, Errington ML, Bliss TVP (1989) Nordihydroguaiaretic acid blocks the synaptic component of long-term potentiation and the associated increases in release of glutamate and arachidonate: anin vivo study in the dentate gyrus of the rat. Neuroscience 30:693–701

    Google Scholar 

  27. Martin LJ, Blackstone CD, Huganir RL, Price DL (1992) Cellular localization of a metabotropic glutamate receptor in rat brain. Neuron 9:259–270

    Google Scholar 

  28. Masu M, Tanabe Y, Tsuchida K, Shigemoto R, Nakanishi S (1991) Sequence and expression of a metabotropic glutamate receptor. Nature 349:760–765

    Google Scholar 

  29. Mayer ML, MacDermott AB, Westbrook GL, Smith SJ, Barker JL (1987) Agonist and voltage-gated calcium entry in cultured mouse spinal cord neurons under voltage clamp measured using arsenazo III. J Neurosci 7:3230–3244

    Google Scholar 

  30. Miller B, Sarantis M, Traynelis SF, Attwell D (1992) Potentiation of NMDA receptor currents by arachidonic acid. Nature 355:722–725

    Google Scholar 

  31. Nishizuka Y (1988) The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature 334:661–665

    Google Scholar 

  32. Schoepp DD, Conn PJ (1993) Metabotropic glutamate receptors in brain function and pathology. Trends Pharmacol Sci 14:13–20

    Google Scholar 

  33. Tapia-Arancibia L, Rage F, Récasens M, Pin JP (1992) NMDA receptor activation stimulates phospholipase A2 and somatostatin release from rat cortical neurons in primary cultures. Eur J Pharmacol 225:253–262

    Google Scholar 

  34. Williams JH, Errington ML, Lynch MA, Bliss TVP (1989) Arachidonic acid induces a long-term activity-dependent enhancement of synaptic transmission in the hippocampus. Nature 341:739–742

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Brain Research Institute, University of Zürich, August Forel-Strasse 1, CH-8029, Zürich, Switzerland

    Anita Lüthi, Beat H. Gähwiler & Urs Gerber

Authors
  1. Anita Lüthi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Beat H. Gähwiler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Urs Gerber
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lüthi, A., Gähwiler, B.H. & Gerber, U. Potentiation of a metabotropic glutamatergic response following NMDA receptor activation in rat hippocampus. Pflügers Arch. 427, 197–202 (1994). https://doi.org/10.1007/BF00585965

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00585965

Key words

Search

Navigation