Metabotropic glutamate receptor dependent EPSP and EPSP-spike potentiation in area CA1 of the submerged rat hippocampal slice

1996 ◽  
Vol 76 (5) ◽  
pp. 3126-3135 ◽  
Author(s):  
N. A. Breakwell ◽  
M. J. Rowan ◽  
R. Anwyl
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Cell Body ◽  
Metabotropic Glutamate Receptor ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Excitatory Postsynaptic Potential ◽  
Area Ca1 ◽  
Gabaa Receptor Antagonist

1. We reexamined the important areas of conflict in (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD]-induced potentiation of the field excitatory postsynaptic potential (EPSP) and, for the first time, investigated the role of mGluRs in EPSP-spike (E-S) coupling. 2. (1S,3R)-ACPD (10 microM) bath applied for 20 min consistently induced a long-lasting potentiation of the dendritic EPSP in area CA1 of submerged rat hippocampal slices, which was considerably faster in onset than described previously. 3. This effect was not associated with any change in presynaptic fiber volley but was dependent on both an intact CA3 connection, because removal of area CA3 blocked (1S,3R)-ACPD-induced potentiation, and also on functional N-methyl-D-aspartate (NMDA) receptors, because (1S,3R)-ACPD-induced potentiation was blocked by inclusion of the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (AP5; 50 microM). 4. (1S,3R)-ACPD induced a long-lasting potentiation of the population spike (PS) amplitude that was consistently larger than that of the EPSP measured in the cell body area. This EPSP-PS (E-S) potentiation was blocked by inclusion of the gamma-aminobuturic acid-A (GABAA) receptor antagonist, picrotoxin (50 microM). 5. E-S potentiation induced by high-frequency stimulation (HFS), which was of the same magnitude as that induced by (1S,3R)-ACPD, was blocked by the mGluR-selective antagonist (+)-alpha-methyl-4-carboxyphenylglycine (+MCPG; 250 microM). +MCPG also blocked HFS-induced long-term potentiation (LTP) of the EPSP measured in the cell body. 6. These results suggest that (1S,3R)-ACPD-induced potentiation is NMDA receptor dependent, contrary to some previous findings, and provide further evidence that both synaptic and E-S potentiation induced by (1S,3R)-ACPD share common mechanisms of expression with HFS-induced LTP. The data emphasize the important role of mGluRs in induction of EPSP LTP and E-S potentiation.

scholarly journals NMDA Receptor-Dependent Metaplasticity by High-Frequency Magnetic Stimulation

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Tursonjan Tokay ◽  
Timo Kirschstein ◽  
Marco Rohde ◽  
Volker Zschorlich ◽  
Rüdiger Köhling
Keyword(s):  
Nmda Receptor ◽  
High Frequency ◽  
Magnetic Stimulation ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Excitatory Postsynaptic Potential ◽  
Metabotropic Glutamate

High-frequency magnetic stimulation (HFMS) can elicit N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal cell synapses. Here, we investigated the priming effect of HFMS on the subsequent magnitude of electrically induced LTP in the CA1 region of rat hippocampal slices using field excitatory postsynaptic potential (fEPSP) recordings. In control slices, electrical high-frequency conditioning stimulation (CS) could reliably induce LTP. In contrast, the same CS protocol resulted in long-term depression when HFMS was delivered to the slice 30 min prior to the electrical stimulation. HFMS-priming was diminished when applied in the presence of the metabotropic glutamate receptor antagonists (RS)-α-methylserine-O-phosphate (MSOP) and (RS)-α-methyl-4-carboxyphenylglycine (MCPG). Moreover, when HFMS was delivered in the presence of the NMDA receptor-antagonist D-2-amino-5-phosphonovalerate (50 µM), CS-induced electrical LTP was again as high as under control conditions in slices without priming. These results demonstrate that HFMS significantly reduced the propensity of subsequent electrical LTP and show that both metabotropic glutamate and NMDA receptor activation were involved in this form of HFMS-induced metaplasticity.

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.

Evidence for Postsynaptic Induction and Expression of NMDA Receptor Independent LTP

1998 ◽  
Vol 79 (3) ◽  
pp. 1167-1182 ◽  
Author(s):  
Lawrence M. Grover
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Ampa Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Glutamate Release ◽  
Field Potential ◽  
Long Term Potentiation ◽  
Separate Experiment ◽  
Tetanic Stimulation

Grover, Lawrence M. Evidence for postsynaptic induction and expression of NMDA receptor independent LTP. J. Neurophysiol. 79: 1167–1182, 1998. Whole cell/patch-clamp and extracellular field potential recordings were used to study the induction and expression of N-methyl-d-aspartate (NMDA) receptor independent long-term potentiation (LTP) in area CA1 of the in vitro rat hippocampus. Induction of NMDA receptor independent LTP was prevented by manipulations that inhibited postsynaptic depolarization during tetanic stimulation: direct hyperpolarization of postsynaptic neurons and bath application of an α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate receptor antagonist. NMDA receptor independent LTP also was blocked by intracellular application of the lidocaine derivative, N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide (QX-314), to CA1 pyramidal neurons. These results complement the previous findings that NMDA receptor independent LTP was inhibited by postsynaptic injections of the calcium chelator 1,2-bis(2-aminophenoxy)ethane- N,N,N′,N′-tetraacetic acid and also was inhibited by a L-type voltage-dependent calcium channel antagonist (nifedipine). Collectively, these data make a strong case for the postsynaptic induction of this form of LTP. This paper also provides evidence for postsynaptic expression of NMDA receptor independent LTP. In an experiment where AMPA- and NMDA-receptor–mediated excitatory postsynaptic potentials (EPSPs) were isolated pharmacologically, LTP was found for only the AMPA-receptor–mediated EPSPs. In a separate experiment, paired-pulse facilitation (PPF) was measured during NMDA receptor independent LTP. Although there was an initial decrease in PPF, suggesting a posttetanic increase in the probability of glutamate release, the change in PPF decayed within 30–40 min of the tetanic stimulation, whereas the magnitude of the LTP was constant over this same time period. In addition, the LTP, but not the corresponding change in PPF, was blocked by the metabotropic glutamate receptor antagonist (±)-α-methyl-4-carboxyphenylglycine. These results are accounted for most easily by a selective increase in postsynaptic AMPA receptor function, but one type of presynaptic modification—an increase in the number of release sites without an overall change in the probability of release—also could account for these results (assuming that the level of glutamate release before LTP induction fully saturated NMDA, but not AMPA, receptors). One possible presynaptic modification, an increase in axon excitability, was ruled out by analysis of the presynaptic fiber volley, which was not increased at any time after LTP induction.

Postnatal maturation of the GABAergic system in rat neocortex

1991 ◽  
Vol 65 (2) ◽  
pp. 247-263 ◽  
Author(s):  
H. J. Luhmann ◽  
D. A. Prince
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Reversal Potential ◽  
Gabab Receptors ◽  
Excitatory Postsynaptic Potential ◽  
Late Response ◽  
Postnatal Maturation ◽  
Inhibitory Circuitry ◽  
Gabaa Receptor Antagonist ◽  
Adult Cells

1. The postnatal maturation of intracortical inhibitory circuitry and the development of responses to applied gamma-aminobutyric acid (GABA) and baclofen were studied in pyramidal and nonpyramidal neurons from layers II and III of the rat primary somatosensory and primary visual cortex, in vitro. 2. Depolarizing spontaneous inhibitory postsynaptic potentials (IPSPs) could be recorded in approximately 70% of the young (postnatal day 4-10; P4-10), juvenile (P11-16), and adult cells (P28-41), respectively, when they were loaded with nitrate. At all ages these spontaneous events could be blocked by application of the GABAA receptor antagonist bicuculline methiodide (BMI), indicating that they were mediated by activation of GABAA receptors. 3. In 122 of the 130 adult cells tested, standardized electrical stimulation of the white matter or layer VI evoked a brief excitatory postsynaptic potential (EPSP), followed by both a fast (f-) and a long-latency (l-)IPSP. Similar stimuli evoked a biphasic IPSP in only 51 of the 98 juvenile and in only 1 of the 56 young neurons studied. The mean peak conductance of the f-IPSP and the l-IPSP increased significantly from 50.2 and 7.5 nS, respectively, in juvenile cells to 84.2 and 18.0 nS, respectively, in adult neurons. 4. Application of the N-methyl-D-aspartate (NMDA) receptor antagonist D-amino-phosphonovaleric acid (D-APV) to juvenile cells induced a significant negative shift in the reversal potential of both the f-IPSP and l-IPSP. This effect was accompanied by a reduction in the peak conductance during these events by 31 and 48%, respectively, indicating that a prominent long-lasting NMDA receptor-mediated EPSP occurs concurrent with the early and late IPSP in immature neurons. In adult neurons, D-APV had no significant effect on the reversal potential of the f- and l-IPSP, although the peak conductance decreased by 20 and 5%, respectively, suggesting that there was a smaller concurrent activation of NMDA receptors in this age group. 5. The functional maturation of GABAA and GABAB receptors was studied using focal applications of GABA to the soma and the apical dendrite. Somatic GABA applications to adult neurons held at depolarized membrane potentials evoked a triphasic response, consisting of 1) a GABAA-mediated hyperpolarizing fast component (GABAhf; reversal potential, -76 mV), 2) a GABAA-mediated depolarizing phase (GABAd; -54 mV), and 3) a hyperpolarizing late response (GABAhl; -80 mV). The GABAd response could be demonstrated at all ages in almost every neuron.(ABSTRACT TRUNCATED AT 400 WORDS)

Oscillatory synaptic interactions between ventroposterior and reticular neurons in mouse thalamus in vitro

1994 ◽  
Vol 72 (4) ◽  
pp. 1993-2003 ◽  
Author(s):  
R. A. Warren ◽  
A. Agmon ◽  
E. G. Jones
Keyword(s):  
Receptor Antagonist ◽  
Gabab Receptor ◽  
Initial Response ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Excitatory Postsynaptic Potential ◽  
Postsynaptic Potential ◽  
Synaptic Interactions ◽  
Gabaa Receptor Antagonist

1. The thalamic reticular nucleus (RTN) has reciprocal connections with relay neurons in the dorsal thalamus. We used whole cell recording in a mouse in vitro slice preparation maintained at room temperature to study the synaptic interactions between the RTN and the ventroposterior thalamic nucleus (VP) during evoked low-frequency oscillations. 2. After a single electrical stimulus of the internal capsule, postsynaptic potentials (PSPs) were recorded in all VP and RTN neurons. In 76% of slices, there was an initial response followed by recurrent PSPs lasting for up to 8 s and with a frequency of approximately 2 Hz in both the VP and RTN. 3. In RTN neurons the initial response consisted of a fast excitatory postsynaptic potential (EPSP) that generated a burst of action potentials. Recurrent PSPs consisted of barrages of EPSPs that often reached burst threshold. The structure of subthreshold EPSP barrages in RTN neurons suggested that they were generated by bursting VP neurons. 4. In VP neurons the stimulus usually evoked a small EPSP followed by a large inhibitory postsynaptic potential (IPSP) that was often followed by a rebound burst. This initial response was often followed by a series of recurrent IPSPs presumably generated by RTN bursts, because intrinsic inhibitory neurons are absent in rodent VP. 5. IPSPs in VP neurons and recurrent EPSPs in RTN neurons were completely abolished by application of a gamma-aminobutyric acid-A (GABAA) receptor antagonist. A GABAB receptor antagonist produced no or little change in either the initial or recurrent response. 6. Recurrent IPSPs in VP neurons were abolished by glutamate receptor antagonists before the initial IPSP, which always remained stimulus dependent. 7. The dependency of recurring IPSPs in VP and recurring EPSPs in RTN upon GABA-mediated inhibition and excitatory amino acid-mediated excitation, plus the character of recurring EPSPs in the RTN strongly suggest that the recurring events were generated through reverse-reciprocal synaptic interactions between VP and RTN neurons. These synaptic interactions most likely play an important role in thalamic oscillations in behavior.

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.

Role of AMPA/kainate receptors in transmission of the sympathetic baroreflex in rat CVLM

1997 ◽  
Vol 272 (3) ◽  
pp. R800-R812 ◽  
Author(s):  
T. Miyawaki ◽  
S. Suzuki ◽  
J. Minson ◽  
L. Arnolda ◽  
J. Chalmers ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Nmda Receptor Antagonist ◽  
Baroreceptor Reflex ◽  
Significant Inhibition ◽  
Kainate Receptors ◽  
Ventrolateral Medulla ◽  
Mk 801 ◽  
Aortic Nerve

We examined the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors within the caudal ventrolateral medulla (CVLM) in mediating the sympathetic baroreceptor reflex in anesthetized and paralyzed rats. Bilateral microinjection into CVLM of either DL-2-amino-5-phosphonovaleric acid [APV; a selective N-methyl-D-aspartic acid (NMDA) receptor antagonist, 20 mM, 100 nl] or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; a selective AMPA/kainate receptor antagonist, 2 mM, 100 nl) alone failed to eliminate the aortic nerve stimulation-evoked hypotension and inhibition of splanchnic sympathetic nerve activity (SNA) or the cardiac-related rhythmicity of SNA. All components of the sympathetic-baroreceptor reflex were abolished when kynurenate (100 mM, 30 nl) or mixtures of APV and CNQX (10 and 1 mM, respectively, 100 or 30 nl) were injected into CVLM. Injection of APV or CNQX into CVLM reduced aortic nerve-evoked inhibitory responses of bulbospinal sympathoexcitatory neurons in rostral ventrolateral medulla (RVLM). The extent of this reduction was variable. Usually, significant inhibition was preserved. In seven RVLM neurons, intravenous injection of MK-801 (NMDA receptor antagonist, 2 mg/kg) failed to eliminate aortic nerve-evoked inhibitory responses. However, inhibitory responses were abolished when CNQX was injected into CVLM after intravenous MK-801. We conclude that both NMDA and AMPA/kainate receptors in CVLM transmit baroreceptor information.

Role of the medullary lateral tegmental field in reflex-mediated sympathoexcitation in cats

2004 ◽  
Vol 286 (3) ◽  
pp. R451-R464 ◽  
Author(s):  
Hakan S. Orer ◽  
Gerard L. Gebber ◽  
Shaun W. Phillips ◽  
Susan M. Barman
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Sympathetic Nerve Activity ◽  
Nmda Receptor Antagonist ◽  
Vagal Afferents ◽  
Reflex Pathways ◽  
Excitatory Responses ◽  
Stimulation Of

We tested the hypothesis that blockade of N-methyl-d-aspartate (NMDA) and non-NMDA receptors on medullary lateral tegmental field (LTF) neurons would reduce the sympathoexcitatory responses elicited by electrical stimulation of vagal, trigeminal, and sciatic afferents, posterior hypothalamus, and midbrain periaqueductal gray as well as by activation of arterial chemoreceptors with intravenous NaCN. Bilateral microinjection of a non-NMDA receptor antagonist into LTF of urethane-anesthetized cats significantly decreased vagal afferent-evoked excitatory responses in inferior cardiac and vertebral nerves to 29 ± 8 and 24 ± 6% of control ( n = 7), respectively. Likewise, blockade of non-NMDA receptors significantly reduced chemoreceptor reflex-induced increases in inferior cardiac (from 210 ± 22 to 129 ± 13% of control; n = 4) and vertebral nerves (from 253 ± 41 to 154 ± 20% of control; n = 7) and mean arterial pressure (from 39 ± 7 to 21 ± 5 mmHg; n = 8). Microinjection of muscimol, but not an NMDA receptor antagonist, caused similar attenuation of these excitatory responses. Sympathoexcitatory responses to the other stimuli were not attenuated by microinjection of a non-NMDA receptor antagonist or muscimol into LTF. In fact, excitatory responses elicited by stimulation of trigeminal, and in some cases sciatic, afferents were enhanced. These data reveal two new roles for the LTF in control of sympathetic nerve activity in cats. One, LTF neurons are involved in mediating sympathoexcitation elicited by activation of vagal afferents and arterial chemoreceptors, primarily via activation of non-NMDA receptors. Two, non-NMDA receptor-mediated activation of other LTF neurons tonically suppresses transmission in trigeminal-sympathetic and sciatic-sympathetic reflex pathways.

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