LTP of AMPA and NMDA Receptor–Mediated Signals: Evidence for Presynaptic Expression and Extrasynaptic Glutamate Spill-Over

We have addressed the expression of long-term potentiation (LTP) in hippocampal CA1 by comparing AMPA and NMDA receptor-(AMPAR- and NMDAR-) mediated postsynaptic signals. We find that potentiation of NMDAR-mediated signals accompanies LTP of AMPAR-mediated signals, and is associated with a change in variability implying an increase in quantal content. Further, tetanic LTP of NMDAR-mediated signals can be elicited when LTP of AMPAR-mediated signals is prevented. We propose that LTP is mainly expressed presynaptically, and that, while AMPARs respond only to glutamate from immediately apposed terminals, NMDARs also sense glutamate released from terminals presynaptic to neighboring cells. We also find that tetanic LTP increases the rate of depression of NMDAR-mediated signals by the use-dependent blocker MK-801, implying an increase in the glutamate release probability. These findings argue for a presynaptic contribution to LTP and for extrasynaptic spill-over of glutamate onto NMDARs.

[1]  R. Nicoll,et al.  The uptake inhibitor L-trans-PDC enhances responses to glutamate but fails to alter the kinetics of excitatory synaptic currents in the hippocampus. , 1993, Journal of neurophysiology.

[2]  C. Stevens,et al.  Presynaptic mechanism for long-term potentiation in the hippocampus , 1990, Nature.

[3]  R. Anwyl,et al.  Potentiation of N-methyl-d-aspartate-receptor-mediated currents detected using the excised patch technique in the hippocampal dentate gyrus , 1995, Neuroscience.

[4]  R. Malinow,et al.  Postsynaptic hyperpolarization during conditioning reversibly blocks induction of long-term potentiation , 1986, Nature.

[5]  R. Malinow,et al.  Direct measurement of quantal changes underlying long-term potentiation in CA1 hippocampus , 1992, Neuron.

[6]  R. Nicoll,et al.  Long-term potentiation: evidence against an increase in transmitter release probability in the CA1 region of the hippocampus. , 1994, Science.

[7]  Laura Ballerini,et al.  Glutamate uptake from the synaptic cleft does not shape the decay of the non-NMDA component of the synaptic current , 1993, Neuron.

[8]  B. Gustafsson,et al.  Hippocampal long-lasting potentiation produced by pairing single volleys and brief conditioning tetani evoked in separate afferents , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[9]  C. Stevens.  Quantal release of neurotransmitter and long-term potentiation , 1993, Cell.

[10]  G. Westbrook,et al.  The time course of glutamate in the synaptic cleft. , 1992, Science.

[11]  R. Nicoll,et al.  Mechanisms generating the time course of dual component excitatory synaptic currents recorded in hippocampal slices , 1990, Neuron.

[12]  R. Zucker,et al.  Long-lasting potentiation and depression without presynaptic activity. , 1996, Journal of neurophysiology.

[13]  R. Nicoll,et al.  Postsynaptic contribution to long-term potentiation revealed by the analysis of miniature synaptic currents , 1992, Nature.

[14]  S. Siegelbaum,et al.  Regulation of hippocampal transmitter release during development and long-term potentiation. , 1995, Science.

[15]  L. Voronin,et al.  Long-term potentiation in the hippocampus , 1983, Neuroscience.

[16]  R. Tsien,et al.  Presynaptic enhancement shown by whole-cell recordings of long-term potentiation in hippocampal slices , 1990, Nature.

[17]  N. Berretta,et al.  Long‐term Potentiation of NMDA Receptor‐mediated EPSP in Guinea‐pig Hippocampal Slices , 1991, The European journal of neuroscience.

[18]  D. Faber,et al.  Applicability of the coefficient of variation method for analyzing synaptic plasticity. , 1991, Biophysical journal.

[19]  A. Konnerth,et al.  Long-term potentiation and functional synapse induction in developing hippocampus , 1996, Nature.

[20]  G Lynch,et al.  Long-term potentiation differentially affects two components of synaptic responses in hippocampus. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[21]  E. Kandel,et al.  Nitric oxide and carbon monoxide produce activity-dependent long-term synaptic enhancement in hippocampus. , 1993, Science.

[22]  K M Harris,et al.  Occurrence and three-dimensional structure of multiple synapses between individual radiatum axons and their target pyramidal cells in hippocampal area CA1 , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  H. Wigström,et al.  The Relative Contribution of NMDA Receptor Channels in the Expression of Long‐term Potentiation in the Hippocampal CA1 Region , 1992, The European journal of neuroscience.

[24]  G. Barrionuevo,et al.  Isolated NMDA receptor-mediated synaptic responses express both LTP and LTD. , 1992, Journal of neurophysiology.

[25]  Christian Rosenmund,et al.  Nonuniform probability of glutamate release at a hippocampal synapse. , 1993, Science.

[26]  R. Nicoll,et al.  Modulation of synaptic transmission and long-term potentiation: effects on paired pulse facilitation and EPSC variance in the CA1 region of the hippocampus. , 1993, Journal of neurophysiology.

[27]  K. Stratford,et al.  Presynaptic release probability influences the locus of long-term potentiation , 1992, Nature.

[28]  M. Mayer,et al.  Structure-activity relationships for amino acid transmitter candidates acting at N-methyl-D-aspartate and quisqualate receptors , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  L. M. Wahl,et al.  Monte Carlo simulation of fast excitatory synaptic transmission at a hippocampal synapse. , 1996, Journal of neurophysiology.

[30]  S. Redman,et al.  Changes in quantal parameters of EPSCs in rat CA1 neurones in vitro after the induction of long‐term potentiation. , 1996, The Journal of physiology.

[31]  E. Kandel,et al.  Activity-dependent long-term enhancement of transmitter release by presynaptic 3′,5′-cyclic GMP in cultured hippocampal neurons , 1995, Nature.

[32]  R. Nicoll,et al.  Bidirectional Control of Quantal Size by Synaptic Activity in the Hippocampus , 1996, Science.

[33]  Dimitri M. Kullmann,et al.  The site of expression of NMDA receptor-dependent LTP: New fuel for an old fire , 1995, Neuron.

[34]  G. Lynch,et al.  Contributions of quisqualate and NMDA receptors to the induction and expression of LTP. , 1988, Science.

[35]  R. Nicoll,et al.  Evidence for all‐or‐none regulation of neurotransmitter release: implications for long‐term potentiation. , 1993, The Journal of physiology.

[36]  Y. Ben-Ari,et al.  Expression of LTP by AMPA and/or NMDA receptors is determined by the extent of NMDA receptors activation during the tetanus. , 1995, Journal of neurophysiology.

[37]  R. Nicoll,et al.  Long-term potentiation is associated with increases in quantal content and quantal amplitude , 1992, Nature.

[38]  R. Malinow,et al.  Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice , 1995, Nature.

[39]  R. Tsien,et al.  Presynaptic component of long-term potentiation visualized at individual hippocampal synapses. , 1995, Science.

[40]  D. Kullmann.  Amplitude fluctuations of dual-component EPSCs in hippocampal pyramidal cells: implications for long-term potentiation. , 1994, Neuron.

[41]  Robert C. Malenka,et al.  Independent mechanisms for long-term depression of AMPA and NMDA responses , 1995, Neuron.

[42]  M. Mauk,et al.  Glutamate iontophoresis induces long-term potentiation in the absence of evoked presynaptic activity , 1993, Neuron.

[43]  C. Yamamoto,et al.  Long‐lasting potentiation of synaptic transmission in the schaffer collateral‐commissural pathway of the guinea pig hippocampus by activation of postsynaptic N‐methyl‐D‐aspartate receptor , 1993, Synapse.

[44]  G. Collingridge,et al.  Synaptic potentiation of dual‐component excitatory postsynaptic currents in the rat hippocampus. , 1995, The Journal of physiology.

[45]  D. Kullmann.  Amplitude fluctuations of , 1994, Neuron.

[46]  C. Stevens,et al.  Changes in reliability of synaptic function as a mechanism for plasticity , 1994, Nature.

[47]  R. Malinow,et al.  The probability of transmitter release at a mammalian central synapse , 1993, Nature.

[48]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[49]  L. Voronin.  On the quantal analysis of hippocampal long-term potentiation and related phenomena of synaptic plasticity , 1993, Neuroscience.

[50]  B. McNaughton,et al.  Long‐term enhancement of CA1 synaptic transmission is due to increased quantal size, not quantal content , 1991, Hippocampus.

[51]  T. Teyler,et al.  Long-term potentiation. , 1987, Annual review of neuroscience.

[52]  R. Tsien,et al.  Long-term potentiation: presynaptic enhancement following postsynaptic activation of Ca(++)-dependent protein kinases. , 1990, Cold Spring Harbor symposia on quantitative biology.

[53]  R. Nicoll,et al.  A persistent postsynaptic modification mediates long-term potentiation in the hippocampus , 1988, Neuron.

[54]  J. Isaac,et al.  Evidence for silent synapses: Implications for the expression of LTP , 1995, Neuron.

[55]  D. Clifford,et al.  Long-term potentiation during whole-cell recording in rat hippocampal slices , 1993, Neuroscience.

[56]  Dimitri M. Kullmann,et al.  Ca2+ Entry via postsynaptic voltage-sensitive Ca2+ channels can transiently potentiate excitatory synaptic transmission in the hippocampus , 1992, Neuron.

[57]  G. Collingridge,et al.  Long-term potentiation of NMDA receptor-mediated synaptic transmission in the hippocampus , 1991, Nature.