Skip to main content
SpringerLink
Log in

Effects of A1 and A2 Adenosine Receptor Antagonists on the Induction and Reversal of Long-Term Potentiation in Guinea Pig Hippocampal Slices of CA1 Neurons

  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

1. Using simultaneous recordings of the field EPSP and the population spike in the CA1 neurons of guinea pig hippocampal slices, we confirmed that delivery of a high-frequency stimulation (tetanus: 100 pulses at 100 Hz) produced robust long-term potentiation of synaptic efficacy (LTP) in two independent components, a synaptic component that increases field excitatory postsynaptic potentials (EPSPs) and a component that results in a larger population spike amplitude for a given EPSP size (E-S potentiation).

2. In the same cells, reversal of LTP (depotentiation; DP) in the field EPSP and in the E-S component is achieved by delivering low-frequency afferent stimulation (LFS:1 Hz, 1000 pulses) 20 min after the tetanus.

3. When the tetanus or LFS was applied to CA1 inputs in the presence of an adenosine A1 receptor antagonist, 8-cyclopentyltheophylline (1 μM), the field EPSP was enhances in LTP and attenuated in DP, while the E-S relationship was not significantly affected in either LTP or DP.

4. When similar experiments were performed using an A2 receptor antagonist, CP-66713 (10 μM), the field EPSP was blocked in LTP but facilitated in DP, while E-S potentiation was enhanced during both LTP and DP.

5. The results show that endogenous adenosine, acting via A1 or A2 receptors, modulates both the synaptic and the E-S components of the induction and reversal of LTP. Based on the results, we discuss the key issue of the contribution of these receptors to the dynamics of neuronal plasticity modification in hippocampal CA1 neurons.

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

  • Abraham, C., Gustafsson, B., and Wigström, H. (1987). Long-term potentiation involves enhanced synaptic excitation relative to synaptic inhibition in guinea pig hippocampus. J. Physiol. (London) 394:367-380.

    Google Scholar 

  • Andersen, P., Sundberg, S. H., Sveen, O., Swann, J. W., and Wigström, H. (1983). Possible mechanisms for long-lasting potentiation of synaptic transmission in hippocampal slices from guinea-pigs. J. Physiol. (London) 302:463-482.

    Google Scholar 

  • Arai, A., Kessler, M., and Lynch, G. (1990). The effects of adenosine on the development of long-term potentiation. Neurosci. Lett. 119:41-44.

    Google Scholar 

  • Asztely, F., and Gustafsson, B. (1994). Dissociation between long-term potentiation and associated change in field EPSP waveform in hippocampal CA1 region: An in vitro study in guinea pig brain slices. Hippocampus 4:148-156.

    Google Scholar 

  • Barrionuevo, G., Schottler, F., and Lynch, G. (1980). The effects of repetitive low frequency stimulation on control and “potentiated” synaptic responses in the hippocampus. Life Sci. 27:2385-2391.

    Google Scholar 

  • Bashir, Z. I., and Collingridge, G. L. (1994). An investigation of depotentiation of long-term potentiation in the CA1 region of the hippocampus. Exp. Brain Res. 100:437-443.

    Google Scholar 

  • Bliss, T. V. P., and Collingridge, G. L. (1993). A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31-39.

    Google Scholar 

  • Bliss, T. V. P., and Gardner-Medwin, A. R. (1973). Long-lasting potentiation of synaptic transmission in the dentate area of the unanesthetized rabbit following stimulation of the perforant path. J. Physiol. 232:357-374.

    Google Scholar 

  • Bliss, T. V. P., and Lømo, T. (1973). Long-lasting potentiation of synaptic transmission in dentate area of the anesthetized rabbit following stimulation of the perforant path. J. Physiol. 232:331-356.

    Google Scholar 

  • Bruns, R. F., Daly, J. W., and Snyder, S. H. (1980). Adenosine receptors in brain membranes: Binding of N6-cyclohexyl[3H]adenosine and 1,3-dimethyl-8-[3H]phenyl-xanthine. Proc. Natl. Acad. Sci. USA 77:5547-5551.

    Google Scholar 

  • Chavez-Noriega, L. E., Bliss, T. V. P., and Halliwell, J. V. (1989). The EPSP-spike (E-S) component of long-term potentiation in the rat hippocampal slice is modulated by GABAergic but not cholinergic mechanisms. Neurosci. Lett. 104:58-64.

    Google Scholar 

  • Collingridge, G. L., Herron, C. E., and Lester, R. A. J. (1988). Frequency dependent N-methyl-Daspartate receptor-mediated synaptic transmission in rat hippocampus. J. Physiol. 399:301-312.

    Google Scholar 

  • Collis, M. G., and Hourani, S. M. O. (1993). Adenosine receptor subtypes. Trends Pharmacol. Sci. 14:360-366.

    Google Scholar 

  • Cunha, R. A., Johansson, B., van der Ploeg, I., Sebastião, A. M., Ribeiro, J. A., and Fredholm, B. B. (1994). Evidence for functionally important adenosine A2a receptors in the rat hippocampus. Brain Res. 649:208-216.

    Google Scholar 

  • Cunha, R. A., Johansson, B., Fredholm, B. B., Ribeiro, J. A., and Sebastião, A. M. (1995). Adenosine A2A receptors stimulate acetylcholine release from nerve terminals of the rat hippocampus. Neurosci. Lett. 196:41-45.

    Google Scholar 

  • Douglas, R., and Goddard, G. (1975). Long-term potentiation of the perforant path-granule cell synapse in the rat hippocampus. Brain Res. 86:205-215.

    Google Scholar 

  • Dunwiddie, T. V., and Fredholm, B. B. (1989). Adenosine A1 receptors inhibit adenylate cyclase activity and neurotransmitter release and hyperpolarize pyramidal neurons in rat hippocampus. J. Pharmacol. Exp. Ther. 249:31-37.

    Google Scholar 

  • Dunwiddie, T. V., Hoffer, B. J., and Fredholm, B. B. (1981). Alklyxanthines elevate hippocampal excitability; Evidence for a role of endogenous adenosine. Naunyn-Schmiedeberg Arch. Pharmacol. 316:326-330.

    Google Scholar 

  • Fastbom, J., Pazos, A., and Palacios, J. M. (1987). The distribution of adenosine A1-receptors and 5'-nucleotidase in the brain of some commonly used experimental animals. Neuroscience 22:813-826.

    Google Scholar 

  • Fredholm, B. B., Jonzon, B., Lindgren, E., and Lindström, K. (1982). Adenosine receptors mediating cyclic AMP production in rat hippocampus. J. Neurochem. 39:165-175.

    Google Scholar 

  • Fujii, S., Saito, K., Ito, K., Miyakawa, H., and Kato, H. (1991). Reversal of long-term potentiation (depotentiation) induced by tetanus stimulation of the input to CA1 neurons of guinea pig hippocampal slices. Brain Res. 555:112-122.

    Google Scholar 

  • Fujii, S., Wakizaka, A., Sekino, Y., Kuroda, Y., Ito, K.-I., Miyakawa, H., and Kato, H. (1992). Adenosine A2 receptor antagonist facilitate the reversal of long-term potentiation (depotentiation) of evoked postsynaptic potentials but inhibits that of population spikes in hippocampal CA1 neurons. Neurosci. Lett. 148:148-150.

    Google Scholar 

  • Fujii, S., Sekino, Y., Kuroda, Y., Sasaki, H., Ito, K.-I., and Kato, H. (1997). 8-Cyclopentyltheophylline, an adenosine A1 receptor antagonist, inhibits the reversal of long-term potentiation in hippocampal CA1 neurons. Eur. J. Pharmacol. 331:9-14.

    Google Scholar 

  • Gustafsson, B., and Wingström, H. (1988). Physiological mechanisms underlying long-term potentiation. Trends Neurosci. 11:156-162.

    Google Scholar 

  • Hess, G., and Gustafsson, B. (1990). Changes in the field excitatory postsynaptic shape induced by tetanization in the guinea-pig hippocampal slice. Neuroscience 37:61-69.

    Google Scholar 

  • Izumi, Y., and Zorumski, C. F. (1995). Developmental change in long-term potentiation in CA1 of rat hippocampal slices. Synapse 20:19-23.

    Google Scholar 

  • Kairiss, E., Abraham, W., Bilkey, D., and Goddard, G. (1987). Field potential evidence for long-term potentiation of feed-forward inhibition in the rat dentate gyrus. Brain Res. 401:87-94.

    Google Scholar 

  • Kuroda, Y. (1991). Activity-dependent release of ATP and adenosine derivatives can trigger molecular cascades for the memory process in human brain. In Imai, S., and Nakazawa, M. (eds.), Roles of Adenosine and Adenine Nucleotides in the Biological System, Elsevier Science, Amsterdam, pp. 605-615.

    Google Scholar 

  • Londos, C., Cooper, D. M. F., and Wolff, J. (1980). Subclasses of external adenosine receptors. Proc. Natl. Acad. Sci. USA 77:2551-2554.

    Google Scholar 

  • Lupica, C. R., Cass, A. W., Zahniser, N. R., and Dunwiddie, T. V. (1990). Effects of adenosine A2 receptor agonist CGS 21680 on in vitro electrophysiology, cAMP formation and dopamine release in rat hippocampus and striatum. J. Pharmacol. Exp. Ther. 252:1134-1141.

    Google Scholar 

  • Sarges, R., Horward, H. R., Browne, R. G., and Koe, B. K. (1990). In Purines in Cell Signaling, Springer-Verlag, New York, pp. 417-418.

  • Schubert, P., Lee, K., West, M., Deadwyler, S., and Lynch, G. (1976). Stimulation-dependent release of 3H-adenosine derivatives from central axon terminals to target neurons. Nature (London) 260:541-542.

    Google Scholar 

  • Sekino, Y., Ito K., Miyakawa, Y., Kato, H., and Kuroda, Y. (1991). Adenosine (A2) antagonist inhibits induction of long-term potentiation of evoked synaptic potentials but not of the population spike in hippocampal CA1 neurons. Biochem. Biophys. Res. Commun. 18(3):1010-1014.

    Google Scholar 

  • Staübli, U., and Lynch, G. (1990). Stable depression of potentiated synaptic responses in the hippocampus with 1-5 Hz stimulation. Brain Res. 513:113-118.

    Google Scholar 

  • Taube, J. S., and Schwartzkroin, P. A. (1988). Mechanisms of long-term potentiation:EPSP/Spike dissociation, intradendritic recordings, and glutamate sensitivity. J. Neurosci. 8:1632-1644.

    Google Scholar 

  • Tomasulo, R., Levy, W., and Steward, O. (1991). LTP-associated EPSP/Spike dissociation in the dentate gyrus: GABAergic and non-GABAergic components. Brain Res. 561:27-34.

    Google Scholar 

  • Tomasulo, R., and Ramirez, J. (1993). Activity-mediated changes in feed-forward inhibition in the dentate commissural pathway: Relationship to EPSP/spike dissociation in the converging perforant path. J. Neurosci. 69:165-173.

    Google Scholar 

  • Van Calker, D., Müller, M., and Hamprecht, B. (1975). Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J. Neurochem. 33:999-1005.

    Google Scholar 

  • White, T. D. (1978). Release of ATP from a synaptosomal preparation by elevated extracellular K+ and by veratridine. J. Neurochem. 30:329-336.

    Google Scholar 

  • Wieraszko, A., Goldsmith, G., and Seyfried, T. N. (1989). Stimulation dependent release of adenosine triphosphate from hippocampal slices. Brain Res. 485:244-250.

    Google Scholar 

  • Wilson, R. (1981). Changes in translation of synaptic excitation to dentate granule cell discharge accompanying long-term potentiation. I. Differences between normal and reinnervated dentate gyrus. J. Neurophysiol. 46:324-338.

    Google Scholar 

  • Wilson, R., Levy, W., and Steward, O. (1981). Changes in translation of synaptic excitation to dentate granule cell discharge accompanying long-term potentiation. II. An evaluation of mechanisms utilizing dentate gyrus dually innervated by surviving ipsilateral and sprouted crossed temporodentate inputs. J. Neurophysiol. 46:339-355.

    Google Scholar 

  • Xu, L., Anwyl, R., and Rowan, M. J. (1998). Spatial exploration induces a persistent reversal of longterm potentiation in rat hippocampus. Nature (London) 394:891-894.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, Yamagata University School of Medicine, Yamagata, 990-23, Japan

    Satoshi Fujii, Hiroshi Kato, Ken-ichi Ito, Satoshi Itoh, Yoshihiko Yamazaki & Hiroshi Sasaki

  2. Department of Molecular and Cellular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashinodai, Fuchu-shi, Tokyo, 183, Japan

    Yoichiro Kuroda

Authors
  1. Satoshi Fujii
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroshi Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ken-ichi Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Satoshi Itoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoshihiko Yamazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hiroshi Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yoichiro Kuroda
    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

Fujii, S., Kato, H., Ito, Ki. et al. Effects of A1 and A2 Adenosine Receptor Antagonists on the Induction and Reversal of Long-Term Potentiation in Guinea Pig Hippocampal Slices of CA1 Neurons. Cell Mol Neurobiol 20, 331–350 (2000). https://doi.org/10.1023/A:1007014226224

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1007014226224

Search

Navigation