Expression of LTP by AMPA and/or NMDA receptors is determined by the extent of NMDA receptors activation during the tetanus

1995 ◽  
Vol 74 (6) ◽  
pp. 2349-2357 ◽  
Author(s):  
L. Aniksztejn ◽  
Y. Ben-Ari
Keyword(s):  
Nmda Receptors ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Excitatory Postsynaptic Potential ◽  
Present Observation ◽  
Tetanic Stimulation ◽  
Strong Intensity ◽  
Weak Intensity ◽  
Term Potentiation ◽  
The One

1. We have tested, in CA1 hippocampal slices, the hypothesis that the expression of long-term potentiation (LTP) by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and/or N-methyl-D-aspartate (NMDA) receptors depends on the degree of NMDA receptors activation during the tetanus. 2. Slices were perfused in an artificial cerebrospinal fluid (ACSF) containing glycine (1 microM), bicuculline (5 microM) and a low Mg2+ concentration (0.3 mM). To measure the AMPA and NMDA receptor-mediated field excitatory postsynaptic potential (fEPSPA and fEPSPN, respectively), we have used the following procedure: control fEPSPA was first measured, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) was then added, and fEPSPN was evoked. CNQX was washed, and once control fEPSPA was recorded, the Schaffer collaterals were tetanized at a weak or a strong intensity. The slope of fEPSPA was measured for 30-45 min followed by that of fEPSPN after the application of CNQX. 3. At a weak intensity (TW, which corresponds to a fEPSPA of approximately 0.3 mV of amplitude and no fEPSPN), the tetanic stimulation generated LTP of fEPSPA (58.7 +/- 8.1% mean +/- SE, n = 9) but no significant potentiation of the fEPSPN (11.2 +/- 2.2%, n = 9). These values were significantly different (P < 0.05, analysis of variance, Fisher test). 4. In 9 of 13 slices, tetanic stimulation of strong intensity (Ts, intensity corresponding to a fEPSPN of approximately 0.3 mV of amplitude) generated LTP of fEPSPN (89.1 +/- 17.2%) but not of fEPSPA (9.44 +/- 2.8%). In the four remaining slices the tetani induce LTP of both fEPSPA and fEPSPN (81.7 +/- 14.7% and 101 +/- 35.6%, respectively, both values were not significantly different). 5. We then examined the effects of decreasing fEPSPN by 50% in LTP generated by Ts and Tw. In the presence of 7-Chlorokynurenate (7Cl(-)-Kyn; 6 microM; n = 6), an antagonist of the allosteric glycine site of the NMDA receptors, Ts generated LTP of fEPSPA (63.2 +/- 8.2%) but not of fEPSPN (12.6 +/- 4.0%). Both values were significantly different. Tw still evoked LTP of fEPSPA but of smaller magnitude (29.8 +/- 6.3%, n = 8) than the one obtained in the absence of the antagonist (58.7 +/- 8.1%). Both values were significantly different. 6. The present observation suggests that l) LTP of fEPSPA has a lower threshold than that of fEPSPN, i.e., stronger activation of NMDA receptors during the tetani is required to induce LTP of fEPSPN than the one required for inducing LTP of fEPSPA; and 2) there is a bell-shaped relationship between the degree of activation of NMDA receptors during the tetani and the magnitude of LTP of the fEPSPA: tetani that generate LTP of fEPSPN have a low probability to induce LTP of fEPSPA. We suggest that AMPA and NMDA components are potentiated through two different presumably postsynaptic processes.

A novel cholinergic induction of long-term potentiation in rat hippocampus

1994 ◽  
Vol 72 (4) ◽  
pp. 2034-2040 ◽  
Author(s):  
J. M. Auerbach ◽  
M. Segal
Keyword(s):  
Synaptic Transmission ◽  
Hippocampal Slices ◽  
Extracellular Recording ◽  
Long Term Potentiation ◽  
Common Mechanism ◽  
Excitatory Postsynaptic Potential ◽  
Tetanic Stimulation ◽  
Term Potentiation ◽  
Bath Application

1. We studied long-term cholinergic effects on synaptic transmission in submerged hippocampal slices using intra- and extracellular recording techniques. 2. Bath application of submicromolar concentrations of carbachol (CCh) produced a gradually developing, long-lasting increase in the CA1 excitatory postsynaptic potential and population spike. This potentiation was blocked by atropine and, hence, named muscarinic long-term potentiation (LTPm). Application of DL-2-amino-5-phosphonovaleric acid had no effect on LTPm, indicating that this phenomenon is N-methyl-D-aspartate receptor independent. 3. These effects of CCh were not likely to be due to the blockade of one of several K+ conductances by the drug; the time and concentration dependence of LTPm were different from those associated with cholinergic blockade of K+ conductances. 4. Removal of extracellular calcium (Cao2+) from the bath blocked synaptic transmission. CCh added in calcium-free medium induced LTPm, which was revealed upon removal of the drug by washing with normal calcium-containing medium. Neither cutting CA1-CA3 connections nor cessation of synaptic stimulation interfered with LTPm induction. 5. Application of thapsigargin or H-7 together with CCh blocked LTPm, suggesting the involvement of intracellular calcium (Cai2+) stores and protein kinases, respectively, in the LTPm mechanism. 6. Subthreshold cholinergic stimulation coupled with subthreshold tetanic stimulation caused LTP. CCh had no effect when administered after the LTP mechanism had been saturated by repeated suprathreshold tetani. Tetanic stimulation failed to cause LTP when applied after LTPm had been induced by CCh. These experiments indicate that tetanus-induced potentiation and LTPm share a common mechanism and provide a direct link between ACh and mechanisms of synaptic plasticity.

scholarly journals Serine Racemase Deletion Affects the Excitatory/Inhibitory Balance of the Hippocampal CA1 Network

2020 ◽  
Vol 21 (24) ◽  
pp. 9447
Author(s):  
Eva Ploux ◽  
Valentine Bouet ◽  
Inna Radzishevsky ◽  
Herman Wolosker ◽  
Thomas Freret ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Reference Memory ◽  
Serine Racemase ◽  
Targeted Deletion ◽  
Term Potentiation ◽  
Hippocampal Ca1 ◽  
The One ◽  
Hippocampal Networks

d-serine is the major co-agonist of N-methyl-D-aspartate receptors (NMDAR) at CA3/CA1 hippocampal synapses, the activation of which drives long-term potentiation (LTP). The use of mice with targeted deletion of the serine racemase (SR) enzyme has been an important tool to uncover the physiological and pathological roles of D-serine. To date, some uncertainties remain regarding the direction of LTP changes in SR-knockout (SR-KO) mice, possibly reflecting differences in inhibitory GABAergic tone in the experimental paradigms used in the different studies. On the one hand, our extracellular recordings in hippocampal slices show that neither isolated NMDAR synaptic potentials nor LTP were altered in SR-KO mice. This was associated with a compensatory increase in hippocampal levels of glycine, another physiologic NMDAR co-agonist. SR-KO mice displayed no deficits in spatial learning, reference memory and cognitive flexibility. On the other hand, SR-KO mice showed a weaker LTP and a lower increase in NMDAR potentials compared to controls when GABAA receptors were pharmacologically blocked. Our results indicate that depletion of endogenous D-serine caused a reduced inhibitory activity in CA1 hippocampal networks, altering the excitatory/inhibitory balance, which contributes to preserve functional plasticity at synapses and to maintain related cognitive abilities.

Developmental increase in CA3-CA1 presynaptic function in the hippocampal slice

1995 ◽  
Vol 73 (5) ◽  
pp. 1821-1828 ◽  
Author(s):  
T. C. Dumas ◽  
T. C. Foster
Keyword(s):  
Hippocampal Slices ◽  
Age Groups ◽  
Extracellular Recording ◽  
Long Term Potentiation ◽  
Developmental Differences ◽  
Excitatory Postsynaptic Potential ◽  
Paired Pulse ◽  
Paired Pulse Facilitation ◽  
Presynaptic Function ◽  
Term Potentiation

1. We recorded extracellular and intracellular CA3-CA1 synaptic responses in hippocampal slices from neonatal rats [postnatal day (P) 15-21 and P29-35]. Presynaptic function was examined by measuring input-output relationships and paired-pulse facilitation and by quantal analysis of minimally evoked responses. 2. Extracellular recording revealed no difference in excitatory postsynaptic potential (EPSP) threshold or the fiber potential response for a given stimulus intensity between the two age groups. However, the slope of the field EPSP was consistently larger in older animals. The increase in EPSP slope was associated with a decrease in paired-pulse facilitation, suggesting an increase in presynaptic function with postnatal development. 3. Extracellular results were confirmed by intracellular recordings that revealed no difference in the minimal stimulation intensity needed to evoke a response, an increase in mean EPSP amplitude with development, and a decrease in paired-pulse facilitation. Quantal parameters were extracted by three separate methods including method of failures, coefficient of variance, and parameter optimization through noise deconvolution. All methods supported presynaptic mediation of facilitation. Comparison of quantal parameters during development indicated an increase in mean quantal content. 4. The results demonstrate that synaptic strength is altered over the course of development because of, at least in part, changes in presynaptic release mechanisms. Developmental differences in presynaptic function provide an explanation of differences in mechanisms for expression of long-term potentiation. The lower initial probability of transmitter release in neonates may permit increased presynaptic change.

2-Deoxyglucose–Induced Long-Term Potentiation in CA1 Is Not Prevented by Intraneuronal Chelator

2000 ◽  
Vol 83 (1) ◽  
pp. 177-180 ◽  
Author(s):  
Yong-Tao Zhao ◽  
Krešimir Krnjević
Keyword(s):  
Ethylene Glycol ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Stratum Radiatum ◽  
Tetanic Stimulation ◽  
Tetraacetic Acid ◽  
Ca1 Neurons ◽  
Term Potentiation ◽  
Stimulation Of

In hippocampal slices, temporary (10–20 min) replacement of glucose with 10 mM 2-deoxyglucose is followed by marked and very sustained potentiation of EPSPs (2-DG LTP). To investigate its mechanism, we examined 2-DG's effect in CA1 neurons recorded with sharp 3 M KCl electrodes containing a strong chelator, 50 or 100 mM ethylene glycol-bis(β-aminoethyl ether)- N, N, N′, N′-tetraacetic acid (EGTA). In most cases, field EPSPs were simultaneously recorded and conventional LTP was also elicited in some cells by tetanic stimulation of stratum radiatum. 2-DG potentiated intracellular EPSP slopes by 48 ± 5.1% (SE) in nine cells recorded with plain KCl electrodes and by 52 ± 6.2% in seven cells recorded with EGTA-containing electrodes. In four of the latter cells, tetanic stimulation (twice 100 Hz for 1 s) failed to evoke LTP (2 ± 1.1%), although field EPSPs were clearly potentiated (by 28 ± 6.9%). Thus unlike tetanic LTP, 2-DG LTP is not readily prevented by postsynaptic intraneuronal injection of EGTA. These findings agree with other evidence that the rise in postsynaptic (somatic) [Ca2+]i caused by 2-DG is not the principal trigger for the subsequent 2-DG LTP and that it may be a purely presynaptic phenomenon.

Intraneuronal [Ca2+] Changes Induced by 2-Deoxy-d-Glucose in Rat Hippocampal Slices

1999 ◽  
Vol 81 (1) ◽  
pp. 174-183 ◽  
Author(s):  
S. Tekkök ◽  
I. Medina ◽  
K. Krnjević
Keyword(s):  
Wistar Rats ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Synergistic Action ◽  
Tetraacetic Acid ◽  
Term Potentiation ◽  
The One ◽  
Peak Increase

Tekkök, S., I. Medina, and K. Krnjević. Intraneuronal [Ca2+] changes induced by 2-deoxy-d-glucose in rat hippocampal slices. J. Neurophysiol. 81: 174–183, 1999. Temporary replacement of glucose by 2-deoxyglucose (2-DG; but not sucrose) is followed by long-term potentiation of CA1 synaptic transmission (2-DG LTP), which is Ca2+-dependent and is prevented by dantrolene or N-methyl-d-aspartate (NMDA) antagonists. To clarify the mechanism of action of 2-DG, we monitored [Ca2+]i while replacing glucose with 2-DG or sucrose. In slices (from Wistar rats) kept submerged at 30°C, pyramidal neurons were loaded with [Ca2+]-sensitive fluo-3 or Fura Red. The fluorescence was measured with a confocal microscope. Bath applications of 10 mM 2-DG (replacing glucose for 15 ± 0.38 min, means ± SE) led to a rapid but reversible rise in fluo-3 fluorescence (or drop of Fura Red fluorescence); the peak increase of fluo-3 fluorescence (Δ F/ F 0), measured near the end of 2-DG applications, was by 245 ± 50% ( n = 32). Isosmolar sucrose (for 15–40 min) had a smaller but significant effect (Δ F/ F 0 = 94 ± 14%, n = 10). The 2-DG–induced Δ F/ F 0 was greatly reduced (to 35 ± 15%, n = 16) by d,l-aminophosphono-valerate (50–100 μM) and abolished by 10 μM dantrolene (−4.0 ± 2.9%, n = 11). A substantial, although smaller effect, of 2-DG persisted in Ca2+-free 1 mM ethylene glycol-bis(β-aminoethyl ether)- N, N, N′, N′-tetraacetic acid (EGTA) medium. Two adenosine antagonists, which do not prevent 2-DG LTP, were also tested; 2-DG–induced Δ F/ F 0 (fluo-3) was not affected by the A1 antagonist 8-cyclopentyl-3,7-dihydro-1,3-dipropyl-1H-purine-2,6-dione (DPCPX 50 nM; 287 ± 38%; n = 20), but it was abolished by the A1/A2 antagonist 8-SPT; 25 ± 29%, n = 19). These observations suggest that 2-DG releases glutamate and adenosine and that the rise in [Ca2+] may be triggered by a synergistic action of glutamate (acting via NMDA receptors) and adenosine (acting via A2b receptors) resulting in Ca2+ release from a dantrolene-sensitive store. The discrepant effects of sucrose and 8-SPT on Δ F/ F 0, on the one hand, and 2-DG LTP, on the other, support other evidence that increases in postsynaptic [Ca2+]i are not essential for 2-DG LTP.

scholarly journals Selective Abolition of the NMDA Component of Long-Term Potentiation in Mice Lacking mGluR5

1998 ◽  
Vol 5 (4) ◽  
pp. 331-343
Author(s):  
Zhengping Jia ◽  
YouMing Lu ◽  
Jeff Henderson ◽  
Franco Taverna ◽  
Carmelo Romano ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Long Term Potentiation ◽  
Mutant Mice ◽  
Excitatory Postsynaptic Potential ◽  
Metabotropic Glutamate ◽  
Term Potentiation

The mechanisms underlying the differential expression of long-term potentiation (LTP) by AMPA and NMDA receptors, are unknown, but could involve G-protein-linked metabotropic glutamate receptors. To investigate this hypothesis we created mutant mice that expressed no metabotropic glutamate receptor 5 (mGluR5), but showed normal development. In an earlier study of these mice we analyzed field-excitatory postsynaptic potential (fEPSPs) in CA1 region of the hippocampus and found a small decrease; possibly arising from changes in the NMDAR-mediated component of synaptic transmission. In the present study we used whole-cell patch clamp recordings of evoked excitatory postsynaptic currents (EPSCs) in CA1 pyramidal neurons to identify the AMPAR- and NMDAR-mediated components of LTP. Recordings from control mice following tetanus, or agonist application (IS, 3R-1-amino-cyclopentane 1,3-dicarboxylic acid) (ACPD), revealed equal enhancement of the AMPA and NMDA receptor-mediated components. In contrast, CA1 neurons from mGluR5-deficient mice showed a complete loss of the NMDA-receptor-mediated component of LTP (LTPNMDA), but normal LTP of the AMPA-receptor-mediated component (LTPAMPA). This selective loss of LTPNMDA was seen in three different genotypic backgrounds and was apparent at all holding potentials (−70 mV to +20 mV). Furthermore, the LTPNMDA deficit in mGluR5 mutant mice could be rescued by stimulating protein kinase C (PKC) with 4β-phorbol-12,13-dibutyrate (PDBu). These results suggest that PKC may couple the postsynaptic mGluR5 to the NMDA-receptor potentiation during LTP, and that this signaling mechanism is distinct from LTPAMPA. Differential enhancement of AMPAR and NMDA receptors by mGluR5 also supports a postsynaptic locus for LTP.

Long-term potentiation in hippocampal slices induced by temporary suppression of glycolysis

1995 ◽  
Vol 74 (6) ◽  
pp. 2763-2766 ◽  
Author(s):  
S. Tekkok ◽  
K. Krnjevic
Keyword(s):  
Nmda Receptors ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Excitatory Postsynaptic Potentials ◽  
Postsynaptic Potentials ◽  
After Effects ◽  
Population Spikes ◽  
Term Potentiation

1. Temporary suppression of glycolysis by 2-deoxy-D-glucose (2-DG)-long enough to abolish CA1 population spikes (PSs) and reduce field excitatory postsynaptic potentials (EPSPs) by two-thirds-is followed by a sustained rebound of EPSPs and PSs (both up by 70-150%). 2. Post 2-DG long-term potentiation (2-DG-LTP) is prevented by block of N-methyl-D-aspartate (NMDA) receptors (NMDARs). Though 2-DG-LTP is normally expressed by other receptors, in presence of picrotoxin 2-DG causes similar LTP of NMDAR-mediated EPSPs. 3. Stimulation at 1 s-1 fully depotentiates 2-DG-LTP. 4. Unlike tetanic LTP, 2-DG-LTP is not pathway-specific, is not occluded by a preceding tetanic LTP (or vice versa) and is insensitive to block of NO synthesis. 5. Hypoglycemic states may have long-lasting after-effects on cerebral synaptic function.

Adenosine Acting on A1 Receptors Protects NO-Triggered Rebound Potentiation and LTP in Rat Hippocampal Slices

2002 ◽  
Vol 87 (4) ◽  
pp. 1781-1789 ◽  
Author(s):  
Christelle L. M. Bon ◽  
John Garthwaite
Keyword(s):  
Synaptic Transmission ◽  
Nmda Receptors ◽  
Hippocampal Slices ◽  
Nmda Antagonist ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
No Donor ◽  
No Formation ◽  
Term Potentiation ◽  
Synthase Inhibitor

Exposure of hippocampal slices to nitric oxide (NO) results in a depression of CA1 synaptic transmission. Under 0.2-Hz stimulation, washout of NO leads to a persistent potentiation that depends on N-methyl-d-aspartate (NMDA) receptors and endogenous NO formation and that occludes tetanus-induced long-term potentiation (LTP). The experiments were initially aimed at determining the relationship between the NO-induced synaptic depression and rebound potentiation. The adenosine A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) partially inhibited the depression produced by the NO donor diethylamine NONOate (300 μM). It also led to a complete block of both the rebound potentiation and the subsequent tetanus-induced LTP. LTP was preserved in the presence of DPCPX if the stimulation frequency was reduced to 0.033 Hz or if the NO application was omitted. The NO-triggered rebound potentiation was restored if the experiment (DPCPX followed by exogenous NO) was conducted in the presence of an NMDA antagonist. The restored potentiation was completely blocked by the NO synthase inhibitor,l-nitroarginine. It is concluded that the NO-induced depression is partially mediated by increased release of endogenous adenosine acting on A1 receptors. Moreover, tonic A1 receptor activation by adenosine protects LTP and the rebound potentiation from being disabled by untimely NMDA receptor activity. Hence, the NO-induced depression and rebound potentiation are linked in the sense that the depression helps to preserve the capacity of the synapses to undergo potentiation. Finally, the results give the first example of exogenous NO eliciting an enduring potentiation of hippocampal synaptic transmission that is dependent on endogenous NO formation, but not on NMDA receptors.

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.

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