scholarly journals AMPA and NMDA Receptors Expressed by Differentiating Xenopus Spinal Neurons

1998 ◽  
Vol 79 (6) ◽  
pp. 2986-2998 ◽  
Author(s):  
Evanna L. Gleason ◽  
Nicholas C. Spitzer
Keyword(s):  
Nmda Receptors ◽  
Glutamate Receptors ◽  
Neuronal Differentiation ◽  
Voltage Clamp ◽  
Neural Development ◽  
Ampa Receptors ◽  
Reversal Potential ◽  
Spinal Neurons ◽  
Neurite Initiation ◽  
Ampa And Nmda Receptors

Gleason, Evanna L. and Nicholas C. Spitzer. AMPA and NMDA receptors expressed by differentiating Xenopus spinal neurons. J. Neurophysiol. 79: 2986–2998, 1998. N-methyl-d-aspartate (NMDA) receptors are often the first ionotropic glutamate receptors expressed at early stages of development and appear to influence neuronal differentiation by mediating Ca2+ influx. Although less well studied, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors also can generate Ca2+ elevations and may have developmental roles. We document the presence of AMPA and NMDA class receptors and the absence of kainate class receptors with whole cell voltage-clamp recordings from Xenopus embryonic spinal neurons differentiated in vitro. Reversal potential measurements indicate that AMPA receptors are permeable to Ca2+ both in differentiated neurons and at the time they first are expressed. The P Ca/ P monocation of 1.9 is close to that of cloned Ca2+-permeable AMPA receptors expressed in heterologous systems. Ca2+ imaging reveals that Ca2+ elevations are elicited by AMPA or NMDA in the absence of Mg2+. The amplitudes and durations of these agonist-induced Ca2+ elevations are similar to those of spontaneous Ca2+ transients known to act as differentiation signals in these cells. Two sources of Ca2+ amplify AMPA- and NMDA-induced Ca2+ elevations. Activation of voltage-gated Ca2+ channels by AMPA- or NMDA-mediated depolarization contributes ∼15 or 30% of cytosolic Ca2+ elevations, respectively. Activation of either class of receptor produces elevations of Ca2+ that elicit further release of Ca2+ from thapsigargin-sensitive but ryanodine-insensitive stores, contributing an additional ∼30% of Ca2+ elevations. Voltage-clamp recordings and Ca2+ imaging both show that these spinal neurons express functional AMPA receptors soon after neurite initiation and before expression of NMDA receptors. The Ca2+ permeability of AMPA receptors, their ability to generate significant elevations of [Ca2+]i, and their appearance before synapse formation position them to play roles in neural development. Spontaneous release of agonists from growth cones is detected with glutamate receptors in outside-out patches, suggesting that spinal neurons are early, nonsynaptic sources of glutamate that can influence neuronal differentiation in vivo.

Voltage-clamp analysis of a Ca2+- and voltage-dependent chloride conductance in cultured mouse spinal neurons

1986 ◽  
Vol 55 (6) ◽  
pp. 1115-1135 ◽  
Author(s):  
D. G. Owen ◽  
M. Segal ◽  
J. L. Barker
Keyword(s):  
Voltage Clamp ◽  
Reversal Potential ◽  
Gamma Aminobutyric Acid ◽  
Spinal Neurons ◽  
Exponential Process ◽  
Voltage Clamp Analysis ◽  
Voltage Dependent ◽  
Inward Currents ◽  
Ca 50 ◽  
O 10

Current and voltage-clamp recordings were made at room temperature from cultured mouse spinal neurons using conventional two-electrode voltage-clamp techniques and electrodes filled with either 3 M KCl, 3 M CsCl, or 3 M Cs2SO4. In the presence of tetraethylammonium and tetrodotoxin, “fast” (rapidly rising and falling) action potentials (FAP) of variable duration were recorded in most neurons. “Slow” (slowly rising and falling) depolarizing potentials (SDP) occurred in 23% of the cells, when using KCl-filled electrodes, and in 82% of the cells with CsCl-filled electrodes. The SDP was frequently preceded by an FAP, although in some cells activation of the SDP occurred before the FAP threshold was reached and in a graded fashion. Both the FAP and SDP were abolished by Cd2+ and other Ca2+ antagonists. In cells exhibiting SDPs, voltage-clamp analysis revealed a sustained (noninactivating) inward current (Isin) during depolarizing steps to potentials more positive than -45 mV. Repolarizing steps resulted in slowly decaying inward tail currents (Itail). Both Isin and Itail were abolished in solutions nominally free of Cao2+, or containing Ca2+-channel antagonists. Bao2+ did not support Isin. The data indicated a U-shaped activation curve for Isin, peaking at about -10 mV. Activation of Isin occurred exponentially with a time constant of approximately 140 ms at -23 mV, becoming faster at more depolarized potentials (ca. 50 ms at -2 mV). Deactivation was slow, giving rise to tail currents lasting seconds. In some cases deactivation could be described by a single exponential process, although frequently the kinetics were more complex. Deactivation was faster at hyperpolarized potentials and sensitive to extracellular ([Ca2+]o), duration of activating voltage steps, and the degree of activation of Isin. Using CsCl-filled electrodes, the reversal potential (Erev) for Isin was -1.7 mV (SEM 3.5 mV, n = 20). Erev always corresponded to the reversal potential for gamma-aminobutyric acid-evoked currents in the same cell. In experiments in which Cs2SO4-filled electrodes were used, Erev was estimated to be -44 mV (SEM 2.3 mV, n = 9). Neither complete substitution of Nao+ with choline ions nor elevation of [K+]o 10-fold significantly affected the estimated Erev. However, substitution of Cl0- with isethionate or methanesulphonate increased the amplitude of inward currents (recorded with CsCl-filled electrodes) and shifted Erev to more depolarized potentials. The results indicate that Cl- are the primary charge carriers for this current and that Cai2+ is required for its activation, leading us to identify it as ICl(Ca).(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals IQSEC2-Associated Intellectual Disability and Autism

2019 ◽  
Vol 20 (12) ◽  
pp. 3038 ◽  
Author(s):  
Nina S. Levy ◽  
George K. E. Umanah ◽  
Eli J. Rogers ◽  
Reem Jada ◽  
Orit Lache ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Nmda Receptors ◽  
Glutamate Receptors ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Neuronal Development ◽  
Catalytic Domain ◽  
Excitatory Synapses ◽  
Ampa Receptor Subunit ◽  
Ion Influx

Mutations in IQSEC2 cause intellectual disability (ID), which is often accompanied by seizures and autism. A number of studies have shown that IQSEC2 is an abundant protein in excitatory synapses and plays an important role in neuronal development as well as synaptic plasticity. Here, we review neuronal IQSEC2 signaling with emphasis on those aspects likely to be involved in autism. IQSEC2 is normally bound to N-methyl-D-aspartate (NMDA)-type glutamate receptors via post synaptic density protein 95 (PSD-95). Activation of NMDA receptors results in calcium ion influx and binding to calmodulin present on the IQSEC2 IQ domain. Calcium/calmodulin induces a conformational change in IQSEC2 leading to activation of the SEC7 catalytic domain. GTP is exchanged for GDP on ADP ribosylation factor 6 (ARF6). Activated ARF6 promotes downregulation of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors through a c-jun N terminal kinase (JNK)-mediated pathway. NMDA receptors, AMPA receptors, and PSD-95 are all known to be adversely affected in autism. An IQSEC2 transgenic mouse carrying a constitutively active mutation (A350V) shows autistic features and reduced levels of surface AMPA receptor subunit GluA2. Sec7 activity and AMPA receptor recycling are presented as two targets, which may respond to drug treatment in IQSEC2-associated ID and autism.

COMPUTER SIMULATION OF COTRANSMISSION BY EXCITATORY AMINO ACIDS AND ACETYLCHOLINE IN THE ENTERIC NERVOUS SYSTEM

2007 ◽  
Vol 07 (02) ◽  
pp. 229-246
Author(s):  
ROUSTEM MIFTAHOF ◽  
N. R. AKHMADEEV
Keyword(s):  
Amino Acids ◽  
Nervous System ◽  
Nmda Receptors ◽  
Enteric Nervous System ◽  
Ampa Receptors ◽  
Excitatory Amino Acids ◽  
Electrical Response ◽  
Ampa And Nmda Receptors ◽  
Irritable Bowel

The role of cotransmission by α-amino-3-hydroxy-5-methyl-4-isoxalose propionic acid (AMPA), L-aspartate, N-methyl-D-aspartate (NMDA), and acetylcholine (ACh) as well as the coexpression of AMPA, NMDA, and nicotinic ACh (nACh) receptors on the electrophysiological activity of the primary sensory (AH) and motor (S) neurons of the enteric nervous system are numerically assessed. Results of computer simulations showed that AMPA and L-Asp alone can induce fast action potentials of short duration on AH and S neurons. Costimulation of nACh and AMPA receptors on the soma of the S neuron resulted in periodic spiking activity. A characteristic biphasic response was recorded from the AH neuron after coactivation of AMPA and NMDA receptors. Glutamate alone acting on NMDA receptors caused prolonged depolarization of the AH neuron and failed to depolarize the S neuron. Cojoint stimulation of the AMPA or nACh receptors was required to produce the effect of glutamate. The overall electrical response of neurons to the activation of NMDA receptors was long-term depolarization. Acetylcholine, AMPA, and glutamate acting alone or cojointly enhanced phasic contraction of the longitudinal smooth muscle. Treatment of neurons with AMPA, NMDA, and nACh receptor antagonists revealed intricate properties of the AH and S neurons. Application of MK-801, D-AP5, and CPP reduced the excitability of the AH neuron and totally abolished electrical activity in the S neuron. The information gained into the cotransmission by excitatory amino acids and acetylcholine in the enteric nervous system may be beneficial in the development of novel effective therapeutics to treat diseases associated with altered visceral nociception, i.e. irritable bowel syndrome.

Distribution, Density, and Clustering of Functional Glutamate Receptors Before and After Synaptogenesis in Hippocampal Neurons

2000 ◽  
Vol 84 (3) ◽  
pp. 1573-1587 ◽  
Author(s):  
Jeffrey R. Cottrell ◽  
Gilles R. Dubé ◽  
Christophe Egles ◽  
Guosong Liu
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Ampa Receptors ◽  
Hippocampal Neurons ◽  
Time Course ◽  
Synapse Formation ◽  
Receptor Activation ◽  
Receptor Density

Postsynaptic differentiation during glutamatergic synapse formation is poorly understood. Using a novel biophysical approach, we have investigated the distribution and density of functional glutamate receptors and characterized their clustering during synaptogenesis in cultured hippocampal neurons. We found that functional α-amino-3-hydroxy-5-methyl-4-isoxazolpropionate (AMPA) and N-methyl-d-aspartate (NMDA) receptors are evenly distributed in the dendritic membrane before synaptogenesis with an estimated density of 3 receptors/μm2. Following synaptogenesis, functional AMPA and NMDA receptors are clustered at synapses with a density estimated to be on the order of 104 receptors/μm2, which corresponds to ∼400 receptors/synapse. Meanwhile there is no reduction in the extrasynaptic receptor density, which indicates that the aggregation of the existing pool of receptors is not the primary mechanism of glutamate receptor clustering. Furthermore our data suggest that the ratio of AMPA to NMDA receptor density may be regulated to be close to one in all dendritic locations. We also demonstrate that synaptic AMPA and NMDA receptor clusters form with a similar time course during synaptogenesis and that functional AMPA receptors cluster independently of activity and glutamate receptor activation, including following the deletion of the NMDA receptor NR1 subunit. Thus glutamate receptor activation is not necessary for the insertion, clustering, and activation of functional AMPA receptors during synapse formation, and this process is likely controlled by an activity-independent signal.

scholarly journals AMPA Receptor-Mediated Miniature Synaptic Calcium Transients in GluR2 Null Mice

2002 ◽  
Vol 88 (1) ◽  
pp. 29-40 ◽  
Author(s):  
Sabrina Wang ◽  
Zhengping Jia ◽  
John Roder ◽  
Timothy H. Murphy
Keyword(s):  
Nmda Receptors ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Calcium Transients ◽  
Receptor Subunit ◽  
Voltage Gated ◽  
Event Frequency ◽  
Ampa And Nmda Receptors ◽  
Two Measures ◽  
Type Receptor

AMPA-type glutamate receptors are normally Ca2+ impermeable due to the expression of the GluR2 receptor subunit. By using GluR2 null mice we were able to detect miniature synaptic Ca2+ transients (MSCTs) associated with AMPA-type receptor-mediated miniature synaptic currents at single synapses in primary cortical cultures. MSCTs and associated Ca2+ transients were monitored under conditions that isolated responses mediated by AMPA or N-methyl-d-aspartate (NMDA) receptors. As expected, addition of the antagonist 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX, 3 μM) blocked the AMPA receptor-mediated MSCTs. Voltage-gated Ca2+channels did not contribute to AMPA MSCTs because CdCl2 (0.1–0.2 mM) did not significantly alter the frequency or the amplitude of the MSCTs. The amplitude of AMPA MSCTs appeared to be regulated independently from event frequency since the two measures were not correlated ( R = 0.023). Synapses were identified that only expressed MSCTs attributed to either NMDA or AMPA receptors. At synapses with only NMDA responses, MSCT amplitude was significantly lower (by 40%) than synapses expressing both NMDA and AMPA responses. At synapses that showed MSCTs mediated by both AMPA and NMDA receptors, the amplitude of the transients in each condition was positively correlated ( R = 0.94). Our results suggest that when AMPA and NMDA receptors are co-expressed at synapses, mechanisms exist to ensure proportional scaling of each receptor type that are distinct from the presynaptic factors controlling the frequency of miniature release.

scholarly journals Electro-acupuncture alleviates motor deficits and maladaptive striatal plasticity in partial-lesioned parkinsonian mice

2020 ◽  
Author(s):  
Wenting Su ◽  
Jianan Yu ◽  
Min Li ◽  
Ke Wang ◽  
Chang Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Synaptic Plasticity ◽  
Nmda Receptors ◽  
Glutamate Receptors ◽  
Motor Skills ◽  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
6 Hydroxydopamine

Abstract Background Parkinson's disease is characterized by abnormal synaptic transmission in the corticostriatal circuit that leads to deficits in motor abilities. Electro-acupuncture has shown to improve the motor behaviors in parkinsonian models. However, the potential mechanisms underlying the electro-acupuncture treatment, specifically in the partial-lesioned model, remain unclear. Methods By utilizing multiple approaches, including electrophysiological, immunohistochemistrical, molecular and behavioral methods, we assessed the effect of electro-acupuncture on the motor dysfunction and striatal synaptic plasticity in a partial-lesioned mouse model induced by intrastriatal injection of 6-hydroxydopamine. Results Electro-acupuncture ameliorated the disrupted gross and fine motor skills in 6-hydroxydopamine-lesioned mice. Notably, electro-acupuncture not only restored the injured corticostriatal long-term potentiation, but also reversed the loss of GluN1-containing NMDA receptors and GluA1-containing AMPA receptors in the striatum. Furthermore, the antagonists selective for AMPA receptors and NMDA receptors blocked the effect of electro-acupuncture on the corticostriatal long-term potentiation in 6-hydroxydopamine-treated mice. Conclusions These data suggest that the postsynaptic glutamate receptors in the striatum undergo the maladaptive changes in the early stage of Parkinson's disease. Electro-acupuncture improves the motor skills via a mechanism involving the modulation of corticostriatal synaptic plasticity and specific glutamate receptors in a partial-lesioned rodent model.

scholarly journals Neurosteroid modulation of ionotropic glutamate receptors and excitatory synaptic transmission

2008 ◽  
pp. S49-S57
Author(s):  
M Sedláček ◽  
M Kořínek ◽  
M Petrovič ◽  
O Cais ◽  
E Adamusová ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Nmda Receptors ◽  
Glutamate Receptors ◽  
Ampa Receptors ◽  
Transmembrane Domain ◽  
Kainate Receptors ◽  
Ionotropic Glutamate Receptors ◽  
Extracellular Loop ◽  
Inhibitory Effects ◽  
Chimeric Receptors

Ionotropic glutamate receptors function can be affected by neurosteroids, both positively and negatively. N-methyl-D-aspartate (NMDA) receptor responses to exogenously applied glutamate are potentiated or inhibited (depending on the receptor subunit composition) by pregnenolone sulphate (PS) and inhibited by pregnanolone sulphate (3alpha5betaS). While PS effect is most pronounced when its application precedes that of glutamate, 3alpha5betaS only binds to receptors already activated. Synaptically activated NMDA receptors are inhibited by 3alpha5betaS, though to a lesser extent than those tonically activated by exogenous glutamate. PS, on the other hand, shows virtually no effect on any of the models of synaptically activated NMDA receptors. The site of neurosteroid action at the receptor molecule has not yet been identified, however, the experiments indicate that there are at least two distinct extracellularly located binding sites for PS mediating its potentiating and inhibitory effects respectively. Experiments with chimeric receptors revealed the importance of the extracellular loop connecting the third and the fourth transmembrane domain of the receptor NR2 subunit for the neurosteroid action. alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors are inhibited by both PS and 3alpha5betaS. These neurosteroids also affect AMPA receptors-mediated synaptic transmission, however, in a rather indirect way, through presynaptically located targets of action.

Stimulation of NMDA and AMPA receptors in the rat nucleus basalis of Meynert affects sleep

1999 ◽  
Vol 277 (5) ◽  
pp. R1488-R1492 ◽  
Author(s):  
Alfredo Manfridi ◽  
Dario Brambilla ◽  
Mauro Mancia
Keyword(s):  
Nmda Receptors ◽  
Glutamate Receptors ◽  
Ampa Receptors ◽  
Slow Wave Sleep ◽  
Nmda Antagonist ◽  
Nucleus Basalis ◽  
Nucleus Basalis Of Meynert ◽  
Mediated Effects ◽  
Polygraphic Recordings ◽  
Freely Moving

The nucleus basalis of Meynert (NBM), a heterogeneous area in the basal forebrain involved in the modulation of sleep and wakefulness, is rich in glutamate receptors, and glutamatergic fibers represent an important part of the input to this nucleus. With the use of unilateral infusions in the NBM, the effects of two different glutamatergic subtype agonists, namely N-methyl-d-aspartic acid (NMDA) and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) hydrobromide, on sleep and wakefulness parameters were determined in freely moving rats by means of polygraphic recordings. NMDA (5 nmol) and AMPA (0.4 nmol) induced an increase in wakefulness and an inhibition of slow-wave sleep. AMPA, but not NMDA, also caused a decrease in desynchronized sleep. These AMPA- and NMDA-mediated effects were counteracted by a pretreatment with the specific NMDA antagonist 2-amino-5-phosphonopentanoic acid (20 nmol) and the specific AMPA antagonist 6,7-dinitroquinoxaline-2,3-dione (2 nmol), respectively. The results reported here indicate that 1) the NBM activation of both NMDA and AMPA glutamate receptors exert a modulatory influence on sleep and wakefulness, and 2) AMPA, but not NMDA receptors, are involved in the modulation of desynchronized sleep, suggesting a different role for NBM NMDA and non-NMDA receptors in sleep modulation.

scholarly journals Study of reinforcing properties of new antagonists of glutamate receptors

2017 ◽  
Vol 15 (1) ◽  
pp. 41-47
Author(s):  
Aleksandr M Potapkin ◽  
Andrei A Lebedev ◽  
Valerii E Gmiro ◽  
Elena V Litasova ◽  
Mariya A Brusina ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Glutamate Receptors ◽  
Ampa Receptors ◽  
Preference Test ◽  
Water Soluble ◽  
Brain Stimulation Reward ◽  
Experimental Medicine ◽  
Mk 801 ◽  
Skinner Box ◽  
Self Stimulation

Reinforcing properties of antagonists of NMDA receptors IEM-1921, IEM-1791, IEM-2181 and the antagonist of AMPA receptors IEM 1460 were investigated. Substances have been synthesized in S.V. Anichkov Dept. of Neuropharmacology Institute of Experimental Medicine. Electrodes were implanted into the lateral hypothalamus for brain stimulation reward. Rats were trained to press a pedal in Skinner box for receiving electric stimulation of the brain. IEM-1921 in doses of 1, 3 and 10 mg/kg enhanced number of pedal pressing and reduced self-stimulation thresholds more than phencyclidine (in doses 1, 3, 10 mg/kg) and MK-801 (in dose 1 and 3 mg/kg). IEM-1460 in doses of 1, 3 and 5 mg/kg reduced the frequency of hypothalamic self-stimulation and enhanced it thresholds. Also we investigated the conditional reinforcing properties of antagonists of glutamate receptors in conditional place preference test (CPP). The antagonist of NMDA receptors IEM 1921 did not cause CPP. The antagonist of AMPA receptors IEM 1460 caused CPP in dose of 3 mg/kg. IEM 1791 didn’t cause CPP. At the same time IEM 2181, the IEM 1791 water-soluble salt, caused CPP. Thus, the antagonist of NMDA of receptors of IEM-1921 increases the reinforcing properties of self-stimulation in rats more than phencyclidine and MK-801.This substance can be used as means analyzer for studying of the reinforcing properties of drugs. Antagonist of NMDA receptors IEM 2181cause CPP and has the conditional reinforcing properties. It is interesting that the antagonists of AMPA receptors IEM 1460 partially cause CPP, but reduced the reinforcing properties of self-stimulation.

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