Differential effects of NMDA–receptor antagonists on long-term potentiation and hypoxic/hypoglycaemic excitotoxicity in hippocampal slices

2000 ◽  
Vol 39 (4) ◽  
pp. 631-642 ◽  
Author(s):  
Tadeusz Frankiewicz ◽  
Andrzej Pilc ◽  
Chris G Parsons
Keyword(s):  
Nmda Receptor ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Nmda Receptor Antagonists ◽  
Receptor Antagonists ◽  
Differential Effects ◽  
Term Potentiation

Long-term Potentiation of NMDA Receptor-mediated EPSP in Guinea-pig Hippocampal Slices

1991 ◽  
Vol 3 (9) ◽  
pp. 850-854 ◽  
Author(s):  
N. Berretta ◽  
F. Berton ◽  
R. Bianchi ◽  
M. Brunelli ◽  
M. Capogna ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Guinea Pig ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Term Potentiation

Two forms of long-term potentiation in area CA1 activate different signal transduction cascades

1996 ◽  
Vol 76 (5) ◽  
pp. 3038-3047 ◽  
Author(s):  
I. Cavus ◽  
T. Teyler
Keyword(s):  
Signal Transduction ◽  
Nmda Receptor ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Protein Kinase Inhibitors ◽  
Area Ca1 ◽  
Term Potentiation

1. The effects of protein kinase inhibitors on N-methyl-D-aspartate (NMDA)-receptor-mediated, voltage-dependent calcium channel (VDCC)-mediated, and 100-Hz long-term potentiation (LTP) were studied in area CA1 of rat hippocampal slices. 2. A 25-Hz tetanus induced a quickly developing potentiation that was blocked by the NMDA antagonist D,L-2-amino-5-phosphonovaleric acid (APV) and was not affected by the L-type VDCC inhibitor nifedipine, suggesting that it was mediated by NMDA receptors (NMDA-LTP). 3. Application of a 200-Hz tetanus in APV induced a slowly developing NMDA-receptor-independent potentiation that was blocked by nifedipine and thus named VDCC-LTP. NMDA- and VDCC-LTP reached comparable magnitudes despite their different induction parameters and developmental kinetics. 4. Bath perfusion of the broad-spectrum serine/threonine kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) blocked NMDA-LTP but not VDCC-LTP, whereas the tyrosine kinase inhibitors genistein and lavendustin A blocked VDCC-LTP but not NMDA-LTP. These results suggest a differential involvement of H-7-sensitive serine/threonine kinases and tyrosine kinases in the two forms of LTP. 5. Tetanization of 200 Hz in control media resulted in a compound potentiation twice as large as NMDA- or VDCC-LTP, implying that the two forms of LTP did not facilitate or reduce each other's expression. The often-used 100-Hz tetanus (1 s twice) induced a potentiation that was comparable in size with the 200-Hz compound LTP. Nifedipine, genistein, and lavendustin A reduced the 100-Hz LTP by approximately 50%, suggesting that this LTP is also a compound potentiation consisting of NMDA- and VDCC-mediated components and their corresponding signal transduction pathways.

scholarly journals Fusion pore modulation as a presynaptic mechanism contributing to expression of long-term potentiation

2003 ◽  
Vol 358 (1432) ◽  
pp. 695-705 ◽  
Author(s):  
Sukwoo Choi ◽  
Jürgen Klingauf ◽  
Richard W. Tsien
Keyword(s):  
Nmda Receptor ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Quantitative Model ◽  
Fusion Pore ◽  
Silent Synapses ◽  
Term Potentiation ◽  
Presynaptic Mechanisms

Working on the idea that postsynaptic and presynaptic mechanisms of long-term potentiation (LTP) expression are not inherently mutually exclusive, we have looked for the existence and functionality of presynaptic mechanisms for augmenting transmitter release in hippocampal slices. Specifically, we asked if changes in glutamate release might contribute to the conversion of ‘silent synapses’ that show N -methyl-D-aspartate (NMDA) responses but no detectable α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) responses, to ones that exhibit both. Here, we review experiments where NMDA receptor responses provided a bioassay of cleft glutamate concentration, using opposition between peak [glu] cleft and a rapidly reversible antagonist, L-AP5. We discuss findings of a dramatic increase in peak [glu] cleft upon expression of pairing-induced LTP (Choi). We present simulations with a quantitative model of glutamatergic synaptic transmission that includes modulation of the presynaptic fusion pore, realistic cleft geometry and a distributed array of postsynaptic receptors and glutamate transporters. The modelling supports the idea that changes in the dynamics of glutamate release can contribute to synaptic unsilencing. We review direct evidence from Renger et al ., in accord with the modelling, that trading off the strength and duration of the glutamate transient can markedly alter AMPA receptor responses with little effect on NMDA receptor responses. An array of additional findings relevant to fusion pore modulation and its proposed contribution to LTP expression are considered.

Cell-Permeable Scavengers of Superoxide Prevent Long-Term Potentiation in Hippocampal Area CA1

1998 ◽  
Vol 80 (1) ◽  
pp. 452-457 ◽  
Author(s):  
Eric Klann
Keyword(s):  
Nmda Receptor ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Manganese Porphyrin ◽  
Area Ca1 ◽  
Term Potentiation ◽  
Hippocampal Area ◽  
Nmda Receptor Activation

Klann, Eric. Cell-permeable scavengers of superoxide prevent long-term potentiation in hippocampal area CA1. J. Neurophysiol. 80: 452–457, 1998. Long-term potentiation (LTP) in hippocampal area CA1 is generally dependent on N-methyl-d-aspartate (NMDA) receptor activation. Reactive oxygen species (ROS), including superoxide, are produced in response to NMDA receptor activation in a number of brain regions, including the hipppocampus. In this study, two cell-permeable manganese porphyrin compounds that mimic superoxide dismutase (SOD) were used to determine whether production of superoxide is required for the induction of LTP in area CA1 of rat hippocampal slices. Incubation of hippocampal slices with either Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) or Mn(III) tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP) prevented the induction of LTP. Incubation of slices with either light-inactivated MnTBAP or light-inactivated MnTMPyP had no effect on induction of LTP. Neither MnTBAP nor MnTMPyP was able to reverse preestablished LTP. These observations suggest that production of superoxide occurs in response to LTP-inducing stimulation and that superoxide is necessary for the induction of LTP.

Enhanced Long-Term Potentiation During Aging Is Masked by Processes Involving Intracellular Calcium Stores

2004 ◽  
Vol 91 (6) ◽  
pp. 2437-2444 ◽  
Author(s):  
Ashok Kumar ◽  
Thomas C. Foster
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Calcium Stores ◽  
Age Related ◽  
Term Potentiation ◽  
Pattern Stimulation ◽  
Old Rats

The contribution of Ca2+ release from intracellular Ca2+ stores (ICS) for regulation of synaptic plasticity thresholds during aging was investigated in hippocampal slices of old (22–24 mo) and young adult (5–8 mo) male Fischer 344 rats. Inhibition of Ca2+-induced Ca2+ release by thapsigargin, cyclopiazonic acid (CPA), or ryanodine during pattern stimulation near the threshold for synaptic modification (5 Hz, 900 pulses) selectively induced long-term potentiation (LTP) to CA1 Schaffer collateral synapses of old rats. Increased synaptic strength was specific to test pathways and blocked by AP-5. Intracellular recordings demonstrated that ICS plays a role in the augmentation of the afterhyperpolarization (AHP) in old rats. The decrease in the AHP by ICS inhibition was reversed by the L-channel agonist, Bay K8644. Under conditions of ICS inhibition and a Bay K8644–mediated enhancement of the AHP, pattern stimulation failed to induce LTP, consistent with the idea that the AHP amplitude shapes the threshold for LTP induction. Finally, ICS inhibition was associated with an increase in the N-methyl-d-aspartate (NMDA) receptor component of synaptic transmission in old animals. This increase in the synaptic response was blocked by the calcineurin inhibitor FK506. The results reveal an age-related increase in susceptibility to LTP-induction that is normally inhibited by ICS and suggest that the age-related shift in Ca2+ regulation and Ca2+-dependent synaptic plasticity is coupled to changes in cell excitability and NMDA receptor function through ICS.

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