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.

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 Silent synapses: what are they telling us about long-term potentiation?

2003 ◽  
Vol 358 (1432) ◽  
pp. 727-733 ◽  
Author(s):  
Dimitri M. Kullmann
Keyword(s):  
Ampa Receptors ◽  
Hippocampal Neurons ◽  
Glutamate Release ◽  
Postsynaptic Density ◽  
Long Term Potentiation ◽  
Silent Synapses ◽  
Term Potentiation ◽  
Silent Synapse ◽  
Cortical Synapses

At several cortical synapses glutamate release events can be mediated exclusively by NMDA receptors, with no detectable contribution from AMPA receptors. This observation was originally made by comparing the trial-to-trial variability of the two components of synaptic signals evoked in hippocampal neurons, and was subsequently confirmed by recording apparently pure NMDA receptor-mediated EPSCs with stimulation of small numbers of axons. It has come to be known as the ‘silent synapse’ phenomenon, and is widely assumed to be caused by the absence of functional AMPA receptors, which can, however, be recruited into the postsynaptic density by long-term potentiation (LTP) induction. Thus, it provides an important impetus for relating AMPA receptor trafficking mechanisms to the expression of LTP, a theme that is taken up elsewhere in this issue. This article draws attention to several findings that call for caution in identifying silent synapses exclusively with synapses without AMPA receptors. In addition, it attempts to identify several missing pieces of evidence that are required to show that unsilencing of such synapses is entirely accounted for by insertion of AMPA receptors into the postsynaptic density. Some aspects of the early stages of LTP expression remain open to alternative explanations.

scholarly journals Expression mechanisms underlying long-term potentiation: a postsynaptic view

2003 ◽  
Vol 358 (1432) ◽  
pp. 721-726 ◽  
Author(s):  
Roger A. Nicoll
Keyword(s):  
Nmda Receptor ◽  
Ampa Receptors ◽  
Glutamate Release ◽  
Glutamate Transporter ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Covalent Modification ◽  
Term Potentiation ◽  
Expression Mechanism

This review summarizes the various experiments that have been carried out to determine if the expression of long-term potentiation (LTP), in particular N -methyl-D-aspartate (NMDA) receptor-dependent LTP, is presynaptic or postsynaptic. Evidence for a presynaptic expression mechanism comes primarily from experiments reporting that glutamate overflow is increased during LTP and from experiments showing that the failure rate decreases during LTP. However, other experimental approaches, such as monitoring synaptic glutamate release by recording astrocytic glutamate transporter currents, have failed to detect any change in glutamate release during LTP. In addition, the discovery of silent synapses, in which LTP rapidly switches on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor function at NMDA-receptor-only synapses, provides a postsynaptic mechanism for the decrease in failures during LTP. It is argued that the preponderance of evidence favours a postsynaptic expression mechanism, whereby NMDA receptor activation results in the rapid recruitment of AMPA receptors as well as a covalent modification of synaptic AMPA receptors.

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.

Caffeine-Mediated Presynaptic Long-Term Potentiation in Hippocampal CA1 Pyramidal Neurons

2003 ◽  
Vol 89 (6) ◽  
pp. 3029-3038 ◽  
Author(s):  
Eduardo D. Martín ◽  
Washington Buño
Keyword(s):  
Nmda Receptors ◽  
Glutamate Release ◽  
Ryanodine Receptors ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Cellular Mechanisms ◽  
Pipette Solution ◽  
Term Potentiation

We report a new form of long-term potentiation (LTP) in Schaffer collateral (SC)-CA1 pyramidal neuron synapses that originates presynaptically and does not require N-methyl-d-aspartate (NMDA) receptor activation nor increases in postsynaptic-free Ca2+. Using rat hippocampal slices, application of a brief “pulse” of caffeine in the bath evoked a nondecremental LTP (CAFLTP) of SC excitatory postsynaptic currents. An increased probability of transmitter release paralleled the CAFLTP, suggesting that it originated presynaptically. The P1 adenosine receptor antagonist 8-cyclopentyltheophylline and the P2 purinoreceptor antagonists suramin and piridoxal-5′-phosphate-azophenyl 2′,4′-disulphonate blocked the CAFLTP. Inhibition of Ca2+ release from caffeine/ryanodine stores by bath-applied ryanodine inhibited the CAFLTP, but ryanodine in the pipette solution was ineffective, suggesting a presynaptic effect of ryanodine. Previous induction of the “classical” LTP did not prevent the CAFLTP, suggesting that the LTP and the CAFLTP have different underlying cellular mechanisms. The CAFLTP is insensitive to the block of NMDA receptors by 2-amino-5-phosphonopentanoic acid and to Ca2+ chelation with intracellular 1,2-bis (2-aminophenoxy) ethane- N,N,N′ ,N′-tetraacetic acid, indicating that neither postsynaptic NMDA receptors nor increases in cytosolic-free Ca2+ participate in the CAFLTP. We conclude that the CAFLTP requires the interaction of caffeine with presynaptic P1, P2 purinoreceptors, and ryanodine receptors and is caused by an increased probability of glutamate release at SC terminals.

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.

scholarly journals Preconditioning In Vivo Ischemia Inhibits Anoxic Long-Term Potentiation and Functionally Protects CA1 Neurons in the Gerbil

1998 ◽  
Vol 18 (3) ◽  
pp. 288-296 ◽  
Author(s):  
Kensuke Kawai ◽  
Tadayoshi Nakagomi ◽  
Takaaki Kirino ◽  
Akira Tamura ◽  
Nobufumi Kawai
Keyword(s):  
Nmda Receptor ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Forebrain Ischemia ◽  
Term Potentiation ◽  
Induced Tolerance

Preconditioning with sublethal ischemia induces tolerance to subsequent lethal ischemia in neurons. We investigated electrophysiologic aspects of the ischemic tolerance phenomenon in the gerbil hippocampus. Gerbils were subjected to 2 minutes of forebrain ischemia (preconditioning ischemia). Some of them were subjected to a subsequent 5 minutes of forebrain ischemia 2 to 3 days after the preconditioning ischemia (double ischemia). Hippocampal slices were prepared from these gerbils subjected to the preconditioning or double ischemia, and field excitatory postsynaptic potentials were recorded from CA1 pyramidal neurons. Capacity for long-term potentiation triggered by tetanic stimulation (tetanic LTP) was transiently inhibited 1 to 2 days after the double ischemia but then recovered. Latency of anoxic depolarization was not significantly different between slices from preconditioned gerbils and those from sham-operated gerbils when these slices were subjected to in vitro anoxia. Postanoxic potentiation of N-methyl-D-aspartate (NMDA) receptor-mediated transmission (anoxic LTP) was inhibited in slices from gerbils 2 to 3 days after the preconditioning ischemia, whereas it was observed in slices from sham-operated gerbils and gerbils 9 days after the preconditioning ischemia. These results suggest that protection by induced tolerance is (1) not only morphologic but also functional, and (2) expressed in inhibiting postischemic overactivation of NMDA receptor-mediated synaptic responses.

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