scholarly journals Pattern-Specific Synaptic Mechanisms in a Multifunctional Network. I. Effects of Alterations in Synapse Strength

2006 ◽  
Vol 95 (3) ◽  
pp. 1323-1333 ◽  
Author(s):  
Steven P. Lieske ◽  
Jan-Marino Ramirez
Keyword(s):  
Nmda Receptor ◽  
Calcium Channels ◽  
Receptor Antagonist ◽  
Nmda Receptor Antagonist ◽  
Specific Effects ◽  
Specific Subset ◽  
Respiratory Network ◽  
Calcium Activated Potassium Channels ◽  
Nmda Glutamate Receptor Antagonist

Many neuronal networks are multifunctional, producing different patterns of activity in different circumstances, but the mechanisms responsible for this reconfiguration are in many cases unresolved. The mammalian respiratory network is an example of such a system. Normal respiratory activity (eupnea) is periodically interrupted by distinct large-amplitude inspirations known as sighs. Both rhythms originate from a single multifunctional neural network, and both are preserved in the in vitro transverse medullary slice of mice. Here we show that the generation of fictive sighs were more sensitive than eupnea to reductions of excitatory synapse strength caused by either the P/Q-type (α1A-containing) calcium channel antagonist ω-agatoxin TK or the non- N-methyl-d-aspartate (NMDA) glutamate receptor antagonist 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX). In contrast, the NMDA receptor antagonist MK-801, while also inhibiting eupnea, increased the occurrence of sighs. This suggests that among the glutamatergic synapses subserving eupneic rhythmogenesis, there is a specific subset—highly sensitive to agatoxin and insensitive to NMDA receptor blockade—that is essential for sighs. Blockade of N-type calcium channels with ω-conotoxin GVIA also had pattern-specific effects: eupneic activity was not affected, but sigh frequency was increased and postsigh apnea decreased. We hypothesize that N-type (α1B) calcium channels selectively coupled to calcium-activated potassium channels contribute to the generation of the postsigh apnea.

Characterization of 3-carboxy-5-phosphono-1,2,3,4-tetrahydroisoquinoline (SC-48981), a potent competitive (NMDA) receptor antagonist, in vitro and in vivo

1992 ◽  
Vol 135 (2) ◽  
pp. 149-152 ◽  
Author(s):  
Michael L. Vazquez ◽  
Danny J. Garland ◽  
Eric T. Sun ◽  
Julie A. Cler ◽  
Steve J. Mick ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Nmda Receptor Antagonist

Mechanisms underlying induction of long-term potentiation in rat medial and lateral perforant paths in vitro

1993 ◽  
Vol 69 (4) ◽  
pp. 1150-1159 ◽  
Author(s):  
A. Colino ◽  
R. C. Malenka
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Intracellular Calcium ◽  
Granule Cells ◽  
Long Term Potentiation ◽  
Nmda Receptor Antagonist ◽  
Perforant Path ◽  
Term Potentiation

1. The mechanisms underlying the induction of long-term potentiation (LTP) in the medial and lateral perforant paths were studied by recording excitatory postsynaptic potentials (EPSPs) from rat dentate granule cells in vitro using extracellular and whole-cell recording techniques. 2. Paired stimuli (interstimulus interval, 50-1,000 ms) resulted in facilitation of the lateral and depression of the medial perforant path-evoked EPSPs, respectively. This physiological difference was used to isolate responses evoked by stimulation of a single path. 3. Tetanic stimulation induced LTP in both pathways, although the magnitude of LTP in the lateral perforant path was significantly less than that in the medial perforant path. Both forms of LTP were blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (D-APV). 4. Buffering intracellular calcium by loading granule cells with the calcium chelator bis (O-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid prevented LTP in both pathways. 5. Pairing of low-frequency (0.25 Hz) afferent stimulation with postsynaptic depolarization induced LTP in the medial but not the lateral perforant path. However, pairing of higher-frequency stimulation (1-4 Hz) with postsynaptic depolarization did potentiate the lateral perforant path-evoked EPSP in some cells. 6. Both the medial and lateral perforant path-evoked EPSPs had two components; a fast component blocked by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and a slower, voltage-dependent component blocked by D-APV. 7. The results indicate that the induction of LTP in both the medial and lateral perforant paths requires activation of postsynaptic NMDA receptors and a rise in intracellular calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Synthesis and Cytotoxic Activity Evaluation of New Cu(I) Complexes of Bis(pyrazol-1-yl) Acetate Ligands Functionalized with an NMDA Receptor Antagonist

2020 ◽  
Vol 21 (7) ◽  
pp. 2616 ◽  
Author(s):  
Maura Pellei ◽  
Luca Bagnarelli ◽  
Lorenzo Luciani ◽  
Fabio Del Bello ◽  
Gianfabio Giorgioni ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Carboxylic Acid ◽  
Receptor Antagonist ◽  
Three Dimensional ◽  
Human Tumor ◽  
Nmda Antagonist ◽  
Nmda Receptor Antagonist ◽  
Ic50 Values ◽  
Drug Resistant Phenotype

In the present article, copper(I) complexes of bis(pyrazol-1-yl) carboxylic acid (LH), bis(3,5-dimethylpyrazol-1-yl) carboxylic acid (L2H), and bis(pyrazol-1-yl) acetates conjugated with an N-methyl-d-aspartate (NMDA) receptor antagonist (LNMDA or L2NMDA) and phosphane ligands (triphenylphosphine or 1,3,5-triaza-7-phosphaadamantane) were synthesized. The selection of an NMDA antagonist for the coupling with LH and L2H was suggested by the observation that NMDA receptors are expressed and play a role in different types of cancer models. All the new complexes showed a significant antitumor activity on a panel of human tumor cell lines of different histology, with cisplatin-sensitive, cisplatin-resistant, or multi-drug-resistant phenotype. Their half maximal inhibitory concentration (IC50) values were in the low- and sub-micromolar range and, in general, significantly lower than that of cisplatin. Interestingly, the fact that all the complexes proved to be significantly more active than cisplatin even in three-dimensional (3D) spheroids of H157 and BxPC3 cancer cells increased the relevance of the in vitro results. Finally, morphological analysis revealed that the most representative complex 8 induced a massive swelling of the endoplasmic reticulum (ER) membrane, which is a clear sign of ER stress.

Functional in vitro characterization of CR 3394: A novel voltage dependent N-methyl-d-aspartate (NMDA) receptor antagonist

2006 ◽  
Vol 50 (3) ◽  
pp. 277-285 ◽  
Author(s):  
Gabriele Losi ◽  
Marco Lanza ◽  
Francesco Makovec ◽  
Roberto Artusi ◽  
Gianfranco Caselli ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Nmda Receptor Antagonist ◽  
In Vitro Characterization ◽  
Voltage Dependent

scholarly journals Nicotinic and Muscarinic Reduction of Unitary Excitatory Postsynaptic Potentials in Sensory Cortex; Dual Intracellular Recording In Vitro

2006 ◽  
Vol 95 (4) ◽  
pp. 2155-2166 ◽  
Author(s):  
Robert B. Levy ◽  
Alex D. Reyes ◽  
Chiye Aoki
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Pyramidal Neurons ◽  
Glutamate Release ◽  
Receptor Activation ◽  
Nmda Receptor Antagonist ◽  
Excitatory Postsynaptic Potentials ◽  
Postsynaptic Potentials ◽  
Sensory Activity

We studied the cholinergic modulation of glutamatergic transmission between neighboring layer 5 regular-spiking pyramidal neurons in somatosensory cortical slices from young rats (P10-P26). Brief bath application of 5–10 μM carbachol, a nonspecific cholinergic agonist, decreased the amplitude of evoked unitary excitatory postsynaptic potentials (EPSPs). This effect was blocked by 1 μM atropine, a muscarinic receptor antagonist. Nicotine (10 μM), in contrast to carbachol, reduced EPSPs in nominally magnesium-free solution but not in the presence of 1 mM Mg+2, indicating the involvement of NMDA receptors. Likewise, when the postsynaptic cell was depolarized under voltage clamp to allow NMDA receptor activation in the presence of 1 mM Mg+2, synaptic currents were reduced by nicotine. Nicotinic EPSP reduction was prevented by the NMDA receptor antagonist d-AP5 (50 μM) and by the nicotinic receptor antagonist mecamylamine (10 μM). Both carbachol and nicotine reduced short-term depression of EPSPs evoked by 10 Hz stimulation, indicating that EPSP reduction happens via reduction of presynaptic glutamate release. In the case of nicotine, several possible mechanisms for NMDAR-dependent EPSP reduction are discussed. As a result of NMDA receptor dependence, nicotinic EPSP reduction may serve to reduce the local spread of cortical excitation during heightened sensory activity.

NMDA receptor antagonist effects of the stereoisomers of β-cyclazocine in rats, in vivo and in vitro

1991 ◽  
Vol 192 (3) ◽  
pp. 337-342 ◽  
Author(s):  
John Church ◽  
John D. Millar ◽  
Martyn G. Jones ◽  
David Lodge
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Nmda Receptor Antagonist

scholarly journals  The effect of memantine on behavioural sensitisation to methamphetamine in mice

2012 ◽  
Vol 57 (No. 10) ◽  
pp. 543-550 ◽  
Author(s):  
L. Landa ◽  
K. Slais ◽  
A. Sulcova
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Repeated Administration ◽  
Nmda Receptor Antagonist ◽  
Behavioural Sensitisation ◽  
Inward Currents ◽  
Nmda Glutamate Receptor ◽  
Psychotropic Effects ◽  
Pre Treatment ◽  
Nmda Glutamate Receptor Antagonist

&nbsp; After repeated administration the psychostimulant methamphetamine (Met) produces a substantial increase in behavioural responses, which is termed behavioural sensitisation. Many studies have reported that N-methyl-d-aspartate (NMDA) receptors play an important role in the development and expression of behavioural sensitisation. Memantine (Mem) is used particularly for the treatment of Alzheimer&rsquo;s disease and acts as a non-competitive NMDA glutamate receptor antagonist, possessing a variety of psychotropic effects. For example, there are studies indicating that memantine prevents the expression of withdrawal symptoms in mice and causes reversal of opioid dependence. Although not all pharmacological mechanisms of memantine have been clarified yet, it is known that memantine inhibits NMDA receptor inward currents. Thus, the present study was designed to assess whether memantine would influence behavioural sensitisation to the stimulatory effects of methamphetamine on mouse locomotion. Mice were randomly allocated into four groups. They were given vehicle on Day 1of the experiment and after five days without application they were administered seven drug daily doses (i.p.) from Day&nbsp;7 to Day 13 of the study, as follows: (a) n<sub>1, 2</sub>: 2.5 mg/kg/day of Met; (b) n<sub>3</sub>: combination Met + Mem at the doses of 2.5 mg/kg/day and 5 mg/kg/day, respectively; (c) n<sub>4</sub>: Mem at the dose of 5 mg/kg/day. On Day 14 mice were given the first &ldquo;challenge treatment&rdquo; (a) n<sub>1</sub>: Met, (b) n<sub>2</sub>: Met + Mem, (c) n<sub>3</sub>: Met, (d) n<sub>4</sub>: Mem. The second &ldquo;challenge treatment&rdquo; was given after a six day wash-out period on Day 21: (a) n<sub>1</sub>: Met, (b) n<sub>2</sub>: Met + Mem, (c) n<sub>3</sub>: Met, (d) n<sub>4</sub>: Mem. Changes in locomotion were measured for a period of 3 min in the Open field on Days 1, 7, 14 and 21 to assess the sensitising phenomenon. Met pre-treatment significantly sensitised to the effects of the challenge doses (n<sub>1</sub>). Mem given alone did not change the measured behavioural parameters after the acute dose but it significantly decreased locomotion after its repeated administration (n<sub>4</sub>). Repeated pre-treatment with the Met + Mem combination (n<sub>3</sub>) did not produce sensitisation after Met challenge doses and similarly, repeated pre-treatment with Met did not induce sensitisation after the challenge dose of Met + Mem (n<sub>2</sub>). Thus, our results suggest that the role of the NMDA receptor antagonist memantine in the development and expression of behavioural sensitisation to Met seems to be an inhibitory one. &nbsp;

Neurotoxicity Mediated by Aberrant Patterns of Synaptic Activity Between Rat Hippocampal Neurons in Culture

1998 ◽  
Vol 80 (5) ◽  
pp. 2688-2698 ◽  
Author(s):  
John R. McLeod ◽  
Maoxing Shen ◽  
Daniel J. Kim ◽  
Stanley A. Thayer
Keyword(s):  
Cell Death ◽  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Hippocampal Neurons ◽  
Cell Voltage ◽  
Nmda Receptor Antagonist ◽  
Synaptic Activity ◽  
Slow Inward Current ◽  
Inward Current

McLeod, John R., Jr., Maoxing Shen, Daniel J. Kim, and Stanley A. Thayer. Neurotoxicity mediated by aberrant patterns of synaptic activity between rat hippocampal neurons in culture. J. Neurophysiol. 80: 2688–2698, 1998. Reducing the extracellular Mg2+ concentration ([Mg2+]o) to 0.1 mM evoked an aberrant pattern of glutamatergic activity in the synaptic network formed by rat hippocampal neurons grown in primary culture. This treatment resulted in a significant increase in neuronal death when maintained for 20–24 h; 0.1 mM [Mg2+]o elicited a stable and repetitive series of intracellular Ca2+ concentration ([Ca2+]i) spikes as indicated by indo-1-based microfluorimetry. Fura-2-based digital imaging experiments found that the [Ca2+]i spikes were synchronized for all the neurons in a given field. Thus electrophysiological recordings from individual cells were reasonable representations of the field as a whole, enabling correlation of electrical activity to viability. Underlying each [Ca2+]i spike was an intense burst of action potentials. Whole cell voltage-clamp experiments showed that a burst was composed of fast action currents superimposed on a slow inward current. The N-methyl-d-aspartate (NMDA) receptor antagonist CGS19755 (10 μM) blocked [Ca2+]i spiking, the slow inward current, and the cell death induced by low [Mg2+]o. The L-type Ca2+ channel antagonist nimodipine (10 μM) blocked [Ca2+]i spiking, all synaptic activity, and the cell death induced by low [Mg2+]o. The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM) exerted variable effects on [Ca2+]i spiking and blocked the slow inward current only when the cells were held at a relatively negative holding potential. CNQX did not afford any protection from 0.1 mM [Mg2+]o-induced neurotoxicity. [Ca2+]i imaging experiments showed that CNQX inhibited [Ca2+]i spiking in a subset of neurons within an active network. Thus, the neurons that were insensitive to CNQX appear to be those that were destined to die. We characterized an in vitro model that allowed us to correlate specific electrophysiological components of glutamatergic synaptic activity to the subsequent viability of the network. A slow NMDA receptor-mediated inward current was required to elicit [Ca2+]i spiking and neurotoxicity. Non-NMDA receptors did not contribute to synaptically mediated cell death in this model. An L-type Ca2+ channel antagonist was neuroprotective when used at concentrations that blocked synaptic activity, suggesting that dendritic L-type Ca2+ channels present a useful target for neuroprotective drugs.

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