Long-term potentiation (LTP), a long-lasting, activity-dependent increase in the strength of synaptic transmission, is one of the most intensively studied forms of synaptic plasticity in the mammalian brain. In the CA1 region of the hippocampus, the induction of LTP is likely to require a rise in postsynaptic calcium levels. The main source for this calcium is influx through the NMDA receptor ionophore, although other potential sources include voltage-dependent calcium channels and release from intracellular stores. Dendritic spines, the sites of synaptic contact, may function to isolate and amplify synaptically mediated increases in postsynaptic calcium. Recent evidence indicates that the magnitude of postsynaptic calcium increase is a critical variable controlling the duration of synaptic enhancement. Although a number of calcium-dependent biochemical processes have been implicated in LTP, determining their exact role remains a challenging experimental problem.
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Aniksztejn L. and Ben-Ari Y. (1991) Novel form of long-term potentiation produced by a K+ channel blocker in the hippocampus.Nature 349, 67–69.
Anwyl R., Mulkeen D., and Rowan M. J. (1989) The role ofN-methyl-d-aspartate receptors in the generation of short-term potentiation in the rat hippocampus.Brain. Res. 503, 148–151.
Ascher P. and Nowak L. (1988) The role of divalent cations in theN-methyl-d-aspartate responses of mouse central neurones in culture.J. Physiol. 399, 247–266.
Bekkers J. M. and Stevens C. F. (1989) NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus.Nature 341, 230–233.
Bliss T. V. P. and Lømo T. (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the performant path.J. Physiol. 232, 331–356.
Collingridge G. L., Kehl S. J., and McLennan H. (1983) Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus.J. Physiol. 334, 33–46.
Gamble E. and Koch C. (1987) The dynamics of free calcium in dendritic spines in response to repetitive synaptic input.Science 236, 1311–1315.
Grover L. M. and Teyler T. J. (1990) Two components of long-term potentiation induced by different patterns of afferent activation.Nature 347, 477–479.
Gustafsson B. and Wigström H. (1988) Physiological mechanisms underlying long-term potentiation.Trends Neurosci. 11, 156–162.
Gustaffson B. and Wigström H. (1990) Basic features of long-term potentiation in the hippocampus.Sem. Neurosci. 2, 321–334.
Harris K. M. and Stevens J. K. (1989) Dendritic spines of CA1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics.J. Neurosci. 9, 2982–2997.
Holmes W. R. (1990) Is the function of dendritic spines to concentrate calcium?Brain Res. 519, 338–342.
Holmes W. R. and Levy W. B. (1990) Insights into associative long-term potentiation from computational models of NMDA receptor-mediated calcium influx and intracellular calcium concentration changes.J. Neurophysiol 63, 1148–1168.
Jahr C. E. and Stevens C. F. (1987) Glutamate activates multiple single channel conductances in hippocampal neurones.Nature 325, 522–525.
Jones O. T., Kunze D. L., and Angelides K. J. (1989) Localization and mobility of ω-conotoxin-sensitive Ca2+ channels in hippocampal CA1 neurons.Science 244, 1189–1193.
Kauer J. A., Malenka R. C., and Nicoll R. A. (1988) NMDA application potentiates synaptic transmission in the hippocampus.Nature 334, 250–252.
Larson J., Wong D., and Lynch G. (1986) Patterned stimulation at the theta frequency is optimal for the induction of hippocampal long-term potentiation.Brain Res. 368, 347–350.
Lisman J. (1989) A mechanism for the Hebb anti-Hebb processes underlying learning and memory.Proc. Natl. Acad. Sci. USA 86, 9574–9578.
Lømo T. (1966) Frequency potentiation of excitatory synaptic activity in the dentate area of the hippocampal formation.Acta Physiol. Scand. 68 (suppl. 277), 128.
Lynch G., Kessler M., Arai A., and Larson J. (1990) The nature and causes of hippocampal long-term potentiation.Prog. Brain Res. 83, 233–250.
Lynch G., Larson J., Kelso S., Barrionuevo G., and Schottler F. (1983) Intracellular injections of EGTA block induction of hippocampal long-term potentiation.Nature 305, 719–721.
MacDermott A. B., Mayer M. L., Westbrook G. L., Smith S. J., and Barker J. (1986) NMDA receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones.Nature 321, 519–522.
Madison D. V., Malenka R. C., and Nicoll R. A. (1991) Mechanisms underlying long-term potentiation of synaptic transmission.Ann. Rev. Neurosci. 14, 379–397.
Malenka R. C. (1991) Postsynaptic factors control the duration of synaptic enhancement in area CA1 of the hippocampus.Neuron 6, 53–60.
Malenka R. C. and Nicoll R. A. (1990) Intracellular signals and LTP.Sem. Neurosci. 2, 335–344.
Malenka R. C., Kauer J. A., Perkel D. J., and Nicoll R. A. (1989) The impact of postsynaptic calcium on synaptic transmission—its role in long-term potentiation.Trends Neurosci. 12, 114–450.
Malenka R. C., Kauer J. A., Zucker R. J., and Nicoll R. A. (1988) Postsynaptic calcium is sufficient for potentiation of hippocampal synaptic transmission.Science 242, 81–84.
Mayer M. L. and Miller R. J. (1990) Excitatory amino acid receptors, second messengers and regulation of intracellular Ca2+ in mammalian neurons.Tr. Pharmacol. Sci. 11, 254–260.
Mayer M. L., MacDermott A. B., Westbrook G. L., Smith S. J., and Barker J. L. (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.
McPherson P. S., Kim Y.-K., Valdivia H., Knudson C. M., Takekura H., Franzini-Armstrong C., Coronado R., and Campbell K. P. (1991) The brain ryanodine receptor: a caffeine-sensitive calcium release channel.Neuron 7, 17–25.
Nicoll R. A., Kauer J. A., and Malenka R. C. (1988) The current excitement in long-term potentiation.Neuron 1, 97–103.
Oberhaus A., Mody I., and Baimbridge K. G. (1989) Dantrolene-Na (Dantrium) blocks induction of long-term potentiation in hippocampal slices.Neurosci. Lett. 98, 172–176.
Perkel D. J., Manabe T., and Nicoll R. A. (1991) Role of membrane potential and calcium in the induction of long-term potentiation (LTP).Soc. Neurosci. Abst. 17, 2.
Racine R. J. and Milgram N. W. (1983) Short-term potentiation phenomena in the rat limbic forebrain.Brain Res. 260, 201–216.
Regehr W. G. and Tank D. W. (1990) Postsynaptic NMDA receptor-mediated calcium accumulation in hippocampal CA1 pyramidal cell dendrites.Nature 345, 807–810.
Regehr W. G., Connor J. A., and Tank D. W. (1989) Optical imaging of calcium accumulation in hippocampal pyramidal cells during synaptic activation.Nature 341, 533–536.
Westenbroek R. E., Ahlijanian M. K., and Catterall W. A. (1990) Clustering of L-type Ca2+ channels at the base of major dendrites in hippocampal pyramidal neurons.Nature 347, 281–284.
Wickens J. (1988) Electrically coupled but chemically isolated synapses: dendritic spines and calcium in a rule for synaptic modification.Prog. Neurobiol. 31, 507–528.
Wickens J. R. and Abraham W. C. (1991) The involvement of L-type calcium channels in heterosynaptic long-term depression in the hippocampus.Neurosci. Lett. 130, 128–132.
Wigström H. and Gustafsson B. (1985) On long-lasting potentiation in the hippocampus: a proposed mechanism for its dependence on coincident pre-and postsynaptic activity.Acta Physiol. Scand. 123, 519–522.
Zador A., Koch C., and Brown T. H. (1990) Biophysical model of a Hebbian synapse.Proc. Natl. Acad. Sci. USA 87, 6718–6722.
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Malenka, R.C. The role of postsynaptic calcium in the induction of long-term potentiation. Mol Neurobiol 5, 289 (1991). https://doi.org/10.1007/BF02935552
- Long-term potentiation (LTP)
- short-term potentiation (STP)
- N-methyl-d-aspartate (NMDA)
- voltage-dependent calcium channel
- intracellular store