Abstract
The NMDA (N-methyl-D-aspartate) class of glutamate receptor plays a critical role in a variety of forms of synaptic plasticity in the vertebrate central nervous system1–5. One extensively studied example of plasticity is long-term potentiation (LTP), a remarkably long-lasting enhancement of synaptic efficiency induced in the hippocampus by brief, high-frequency stimulation of excitatory synapses. LTP is a strong candidate for a cellular mechanism of learning and memory. The site of LTP induction appears to be the postsynaptic cell and induction requires both activation of NMDA receptors by synaptically released glutamate6 and depolarization of the postsynaptic membrane7–9. It is proposed that this depolarization relieves a voltage-dependent Mg2+ block of the NMDA receptor channel, resulting in increased calcium influx10,11 which is the trigger for the induction of LTP1,12,13. This model predicts that application of a large depolarizing dose of NMDA should be sufficient to evoke LTP. In agreement with a previous study6, we have found that NMDA or glutamate application does potentiate synaptic transmission in the hippocampus. This agonist-induced potentiation is, however, decremental and short-lived, unlike LTP. It is occluded shortly after the induction of LTP and a similar short-term potentiation can be evoked by synaptically released glutamate. We thus propose that LTP has two components, a short-term, decremental component which can be mimicked by NMDA receptor activation, and a long-lasting, non-decremental component which, in addition to requiring activation of NMDA receptors, requires stimulation of presynaptic afferents.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Collingridge, G. L. & Bliss, T. V. P. Trends Neurosci. 10, 288–293 (1987).
Kleinschmidt, A., Bear, M. F. & Singer, W. Science 238, 355–358 (1987).
Cline, H. T., Debski, E. A. & Constantine-Paton, M. Proc. natn. Acad. Sci. U.S.A. 84, 4342–4345 (1987).
Stelzer, A., Slater, N. T. & tenBruggencate, G. Nature 326, 698–701 (1987).
Mody, I. & Heinemann, U. Nature 326, 701–704 (1987).
Collingridge, G. L., Kehl, S. J. & McLennan, H. J. Physiol. Lond. 334, 33–46 (1983).
Gustafsson, B., Wigström, H., Abraham, W. C. & Huang, Y.-Y. J. Neurosci. 7, 774–780 (1987).
Malinow, R. & Miller, J. P. Nature 320, 529–530 (1986).
Gustafsson, B. & Wigström, H. J. Neurosci. 6, 1575–1582 (1986).
Mayer, M. L., Westbrook, G. L. & Guthrie, P. B. Nature 309, 262–263 (1984).
Nowak, L., Bregestovski, P., Ascher, P., Herbet, A. & Prochiantz, A. Nature 307, 462–465 (1984).
Lynch, G., Larson, J., Kelso, S., Barrionuevo, G. & Schottler, F. Nature 305, 719–721 (1983).
Wigström, H. & Gustafsson, B. J. Physiol. Paris 81, 228–236 (1986).
Collingridge, G. L., Kehl, S. J. & McLennan, H. J. Physiol., Lond. 334, 19–31 (1983).
Watkins, J. C. & Evans, R. H. A. Rev. Pharmac. Tox. 21, 165–204 (1981).
Kauer, J. A., Malenka, R. C. & Nicoll, R. A. J. Physiol, Lond. 398, 23P (1988).
Malenka, R. C., Madison, D. V. & Nicoll, R. A. Nature 321, 175–177 (1986).
Akers, R. E., Lovinger, D. M., Colley, P. A., Linden, D. J. & Routtenberg, A. Science 231, 587–489 (1986).
Malenka, R. C., Ayoub, G. S. & Nicoll, R. A. Brain Res. 403, 198–203 (1987).
Hu, G.-Y. et al. Nature 328, 426–429 (1987).
Lovinger, D., Wong, K., Murakami, K. & Routtenberg, A. Brain Res. 436, 177–183 (1987).
Malinow, R., Madison, D. V. & Tsien, R. W. Biophys. J. 53, 429a (1988).
Madison, D. V., Malinow, R. & Tsien, R. W. J. Physiol., Lond. 398, 18P (1988).
Bliss, T. V. P. & Lynch, M. A. in Long-term Potentiation: Mechanisms and Key Issues (eds Landfield, P. W. & Deadwyler, S. A.) 3–72 (Liss, New York, 1988)
Hopkins, W. F. & Johnston, D. Science 226, 350–352 (1984).
Harris, E. W. & Cotman, C. W. Neurosci. Lett. 70, 132–137 (1986).
Kauer, J. A. & Nicoll, R. A. Exp. Brain Res. (suppl.) (in the press).
Bear, M. F. & Singer, W. Nature 320, 172–175 (1985).
Nicoll, R. A. & Alger, B. E. J. Neurosci. Meth. 4, 153–156 (1981).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kauer, J., Malenka, R. & Nicoll, R. NMDA application potentiates synaptic transmission in the hippocampus. Nature 334, 250–252 (1988). https://doi.org/10.1038/334250a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/334250a0
This article is cited by
-
The 1980s: d-AP5, LTP and a Decade of NMDA Receptor Discoveries
Neurochemical Research (2019)
-
Molecular mechanisms of group I metabotropic glutamate receptor mediated LTP and LTD in basolateral amygdala in vitro
Psychopharmacology (2017)
-
Calcium activated adenylyl cyclase AC8 but not AC1 is required for prolonged behavioral anxiety
Molecular Brain (2016)
-
Identification and characterization of PPARα ligands in the hippocampus
Nature Chemical Biology (2016)
-
Repeated Mild Traumatic Brain Injury Causes Chronic Neuroinflammation, Changes in Hippocampal Synaptic Plasticity, and Associated Cognitive Deficits
Journal of Cerebral Blood Flow & Metabolism (2014)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.