scholarly journals Chemokine CCL2 enhances NMDA receptor-mediated excitatory postsynaptic current in rat hippocampal slices-a potential mechanism for HIV-1-associated neuropathy?

2016 ◽  
Vol 11 (2) ◽  
pp. 306-315 ◽  
Author(s):  
Yan Zhou ◽  
Hongmei Tang ◽  
Huangui Xiong
Keyword(s):  
Nmda Receptor ◽  
Hippocampal Slices ◽  
Potential Mechanism ◽  
Excitatory Postsynaptic Current ◽  
Hiv 1

scholarly journals Ketamine Produces a Long-Lasting Enhancement of CA1 Neuron Excitability

2021 ◽  
Vol 22 (15) ◽  
pp. 8091
Author(s):  
Grace Jang ◽  
M. Bruce MacIver
Keyword(s):  
Nmda Receptor ◽  
Potassium Channel ◽  
Receptor Antagonist ◽  
Hippocampal Slices ◽  
Nmda Receptor Antagonist ◽  
Channel Block ◽  
Mk 801 ◽  
Ca1 Region ◽  
Excitatory Transmission ◽  
Ketamine Anesthesia

Ketamine is a clinical anesthetic and antidepressant. Although ketamine is a known NMDA receptor antagonist, the mechanisms contributing to antidepression are unclear. This present study examined the loci and duration of ketamine’s actions, and the involvement of NMDA receptors. Local field potentials were recorded from the CA1 region of mouse hippocampal slices. Ketamine was tested at antidepressant and anesthetic concentrations. Effects of NMDA receptor antagonists APV and MK-801, GABA receptor antagonist bicuculline, and a potassium channel blocker TEA were also studied. Ketamine decreased population spike amplitudes during application, but a long-lasting increase in amplitudes was seen during washout. Bicuculline reversed the acute effects of ketamine, but the washout increase was not altered. This long-term increase was statistically significant, sustained for >2 h, and involved postsynaptic mechanisms. A similar effect was produced by MK-801, but was only partially evident with APV, demonstrating the importance of the NMDA receptor ion channel block. TEA also produced a lasting excitability increase, indicating a possible involvement of potassium channel block. This is this first report of a long-lasting increase in excitability following ketamine exposure. These results support a growing literature that increased GABA inhibition contributes to ketamine anesthesia, while increased excitatory transmission contributes to its antidepressant effects.

Glycine regulation of synaptic NMDA receptors in hippocampal neurons

1996 ◽  
Vol 76 (5) ◽  
pp. 3415-3424 ◽  
Author(s):  
K. S. Wilcox ◽  
R. M. Fitzsimonds ◽  
B. Johnson ◽  
M. A. Dichter
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Hippocampal Neurons ◽  
Time Course ◽  
Hippocampal Slices ◽  
Maximal Effect ◽  
Patch Clamp Technique ◽  
Whole Cell Patch Clamp ◽  
Dissociated Cell Culture ◽  
Cultured Hippocampal Neurons

1. Although glycine has been identified as a required coagonist with glutamate at N-methyl-D-aspartate (NMDA) receptors, the understanding of glycine's role in excitatory synaptic neurotransmission is quite limited. In the present study, we used the whole cell patch-clamp technique to examine the ability of glycine to regulate current flow through synaptic NMDA receptors at excitatory synapses between cultured hippocampal neurons and in acutely isolated hippocampal slices. 2. These studies demonstrate that the glycine modulatory site on the synaptic NMDA receptor is not saturated under baseline conditions and that increased glycine concentrations can markedly increased NMDA-receptor-mediated excitatory postsynaptic currents (EPSCs) in hippocampal neurons in both dissociated cell culture and in slice. Saturation of the maximal effect of glycine takes place at different concentrations for different cells in culture, suggesting the presence of heterogenous NMDA receptor subunit compositions. 3. Bath-applied glycine had no effect on the time course of EPSCs in either brain slice or culture, indicating that desensitization of the NMDA receptor is not prevented by glycine over the time course of an EPSC. 4. When extracellular glycine concentration is high, all miniature EPSCs recorded in the cultured hippocampal neurons contained NMDA components, indicating that segregation of non-NMDA receptors at individual synaptic boutons does not occur.

Transient Removal of Extracellular Mg2+ Elicits Persistent Suppression of LTP at Hippocampal CA1 Synapses Via PKC Activation

2000 ◽  
Vol 84 (3) ◽  
pp. 1279-1288 ◽  
Author(s):  
Kuei-Sen Hsu ◽  
Wen-Chia Ho ◽  
Chiung-Chun Huang ◽  
Jing-Jane Tsai
Keyword(s):  
Nmda Receptor ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Suppressive Effect ◽  
Dependent Protein Kinase ◽  
Dependent Protein

Previous work has shown that seizure-like activity can disrupt the induction of long-term potentiation (LTP). However, how seizure-like event disrupts the LTP induction remains unknown. To understand the cellular and molecular mechanisms underlying this process better, a set of studies was implemented in area CA1 of rat hippocampal slices using extracellular recording methods. We showed here that prior transient seizure-like activity generated by perfused slices with Mg2+-free artificial cerebrospinal fluid (ACSF) exhibited a persistent suppression of LTP induction. This effect lasted between 2 and 3 h after normal ACSF replacement and was specifically inhibited by N-methyl-d-aspartate (NMDA) receptor antagonistd-2-amino-5-phosphovaleric acid (d-APV) and L-type voltage-operated Ca2+ channel (VOCC) blocker nimodipine, but not by non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In addition, this suppressive effect was specifically blocked by the selective protein kinase C (PKC) inhibitor NPC-15437. However, neither Ca2+/calmodulin-dependent protein kinase II inhibitor KN-62 nor cAMP-dependent protein kinase inhibitor Rp-adenosine 3′,5′-cyclic monophosphothioate (Rp-cAMPS) affected this suppressive effect. This persistent suppression of LTP was not secondary to the long-lasting changes in NMDA receptor activation, because the isolated NMDA receptor–mediated responses did not show a long-term enhancement in response to a 30-min Mg2+-free ACSF application. Additionally, in prior Mg2+-free ACSF–treated slices, the entire frequency-response curve of LTP and long-term depression (LTD) is shifted systematically to favor LTD. These results suggest that the increase of Ca2+ influx through NMDA channels and L-type VOCCs in turn triggering a PKC-dependent signaling cascade is a possible cellular basis underlying this seizure-like activity-induced inhibition of LTP.

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.

On the synchronous activity induced by 4-aminopyridine in the CA3 subfield of juvenile rat hippocampus

1993 ◽  
Vol 70 (3) ◽  
pp. 1018-1029 ◽  
Author(s):  
M. Avoli ◽  
C. Psarropoulou ◽  
V. Tancredi ◽  
Y. Fueta
Keyword(s):  
Nmda Receptor ◽  
Gabaa Receptor ◽  
Action Potentials ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Occurrence Rate ◽  
Gamma Aminobutyric Acid ◽  
Synchronous Activity ◽  
Ca3 Pyramidal Cells

1. Extracellular field potential and intracellular recordings were made in the CA3 subfield of hippocampal slices obtained from 10- to 24-day-old rats during perfusion with artificial cerebrospinal fluid (ACSF) containing the convulsant 4-aminopyridine (4-AP, 50 microM). 2. Three types of spontaneous, synchronous activity were recorded in the presence of 4-AP by employing extracellular microelectrodes positioned in the CA3 stratum (s.) radiatum: first, inter-ictal-like discharges that lasted 0.2-1.2 s and had an occurrence rate of 0.3-1.3 Hz; second, ictal-like events (duration: 3-40 s) that occurred at 4-38 x 10(-3) Hz; and third, large-amplitude (up to 8 mV) negative-going potentials that preceded the onset of the ictal-like events and thus appeared to initiate them. 3. None of these synchronous activities was consistently modified by addition of antagonists of the N-methyl-D-aspartate (NMDA) receptor to the ACSF. In contrast, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 2-10 microM) reversibly blocked interictal- and ictallike discharges. The only synchronous, spontaneous activity recorded in this type of medium consisted of the negative-going potentials that were abolished by the GABAA receptor antagonists bicuculline methiodide (5-20 microM) or picrotoxin (50 microM). Hence they were mediated through the activation of the GABAA receptor. 4. Profile analysis of the 4-AP-induced synchronous activity revealed that the gamma-aminobutyric acid (GABA)-mediated field potential had maximal negative amplitude in s. lacunosum-moleculare, attained equipotentiality at the border between s. radiatum and s. pyramidale, and became positive-going in s. oriens. These findings indicated that the GABA-mediated field potential presumably represented a depolarization occurring in the dendrites of CA3 pyramidal cells. 5. This conclusion was supported by intracellular analysis of the 4-AP-induced activity. The GABA-mediated potential was reflected by a depolarization of the membrane of CA3 pyramidal cells that triggered a few variable-amplitude, fractionated spikes or fast action potentials. By contrast, the ictal-like discharge was associated with a prolonged depolarization during which repetitive bursts of action potentials occurred. Short-lasting depolarizations with bursts of action potentials occurred during each interictal-like discharge. 6. The GABA-mediated potential recorded intracellularly in the presence of CNQX consisted of a prolonged depolarization (up to 12 s) that was still capable of triggering a few fast action potentials and/or fractionated spikes.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Intracellular expression of Tat alters mitochondrial functions in T cells: a potential mechanism to understand mitochondrial damage during HIV-1 replication

Retrovirology ◽  
2015 ◽  
Vol 12 (1) ◽  
Author(s):  
Sara Rodríguez-Mora ◽  
Elena Mateos ◽  
María Moran ◽  
Miguel Ángel Martín ◽  
Juan Antonio López ◽  
...  
Keyword(s):  
T Cells ◽  
Mitochondrial Damage ◽  
Potential Mechanism ◽  
Mitochondrial Functions ◽  
Intracellular Expression ◽  
Hiv 1

scholarly journals NMDA Receptor Activation Mediates Hydrogen Peroxide–Induced Pathophysiology in Rat Hippocampal Slices

2002 ◽  
Vol 87 (6) ◽  
pp. 2896-2903 ◽  
Author(s):  
Marat V. Avshalumov ◽  
Margaret E. Rice
Keyword(s):  
Nmda Receptor ◽  
Oxidative Damage ◽  
Synaptic Transmission ◽  
Glutamate Uptake ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Receptor Activation ◽  
Nmda Receptor Antagonist ◽  
Ros Generation ◽  
Progressive Degeneration

Endogenous reactive oxygen species (ROS) can act as modulators of neuronal activity, including synaptic transmission. Inherent in this process, however, is the potential for oxidative damage if the balance between ROS production and regulation becomes disrupted. Here we report that inhibition of synaptic transmission in rat hippocampal slices by H2O2 can be followed by electrical hyperexcitability when transmission returns during H2O2 washout. As in previous studies, H2O2exposure (15 min) reversibly depressed the extracellular population spike (PS) evoked by Schaffer collateral stimulation. Recovery of PS amplitude, however, was typically accompanied by mild epileptiform activity. Inclusion of ascorbate (400 μM) during H2O2 washout prevented this pathophysiology. No protection was seen with isoascorbate, which is a poor substrate for the stereoselective ascorbate transporter and thus remains primarily extracellular. Epileptiform activity was also prevented by the N-methyl-d-aspartate (NMDA) receptor antagonist, dl-2-amino-5-phosphonopentanoic acid (AP5) during H2O2washout. Once hyperexcitability was induced, however, AP5 did not reverse it. When present during H2O2 exposure, AP5 did not alter PS depression by H2O2but did inhibit the recovery of PS amplitude seen during pulse-train stimulation (10 Hz, 5 s) in H2O2. Inhibition of glutamate uptake by l- trans-2,4-pyrrolidine dicarboxylate (PDC; 50 μM) during H2O2washout markedly enhanced epileptiform activity; coapplication of ascorbate with PDC prevented this. These data indicate that H2O2 exposure can cause activation of normally silent NMDA receptors, possibly via inhibition of redox-sensitive glutamate uptake. When synaptic transmission returns during H2O2 washout, enhanced NMDA receptor activity leads to ROS generation and consequent oxidative damage. These data reveal a pathological cycle that could contribute to progressive degeneration in neurological disorders that involve oxidative stress, including cerebral ischemia.

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