6,7-Dinitro-quinoxaline-2,3-dion and 6-nitro,7-cyano-quinoxaline-2,3-dion antagonise responses to NMDA in the rat spinal cord via an action at the strychnine-insensitive glycine receptor

Birch, P.J.; Grossman, Carol J.; Hayes, Ann G.

doi:10.1016/0014-2999(88)90163-x

Cited by 193 publications

(80 citation statements)

References 6 publications

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“…The possibility can be ruled out, however, that a cross-effect between the two antagonists occurred. Although CNQX may act on NMDA receptors via the glycine site, this requires much higher concentrations (3 X lo-' M; Birch et al, 1988) than what we used to block the synaptic drive. With the antagonist concentrations used here, however, it can be assumed on the basis of two arguments that an almost complete blockade of the receptors was obtained: (1) the complete disappearance of the EPSPs elicited by the sensory afferent stimulation in the presence of AP-5 and CNQX (see Material and Methods, data not shown); and (2) the effect of AP-5 and CNQX on the locomotor-like rhythm (Cazalets et al, 1992;Sqalli-Houssaini et al, 1993b), which was abolished completely at these concentrations.…”

Section: Lumbar Spinal Cordmentioning

confidence: 99%

The synaptic drive from the spinal locomotor network to motoneurons in the newborn rat

1996

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The nature of the synaptic drive from the locomotor spinal network onto the motoneurons was studied in the newborn rat.For this purpose, an in vitro isolated spinal cord preparation of newborn rat was used. The recording chamber was partitioned with Vaseline walls to separate the Ll/L2 lumbar segments, in which the spinal locomotor network is located, from the motoneurons in the lower lumbar segments. Locomotor-like activity was induced by bath-applying a mixture of serotonin and NMDA to segments LllL2. In this way, the synaptic activity could be modified at the lower lumbar level without affecting the motor pattern. The drive elicited onto the motoneurons during sequences of locomotor-like activity, which was monitored by performing intracellular recordings, consisting of an inhibitory component followed by an excitatory component. The inhibitory synaptic volley was reversed at a membrane potential of -60 mV with K acetate electrodes, whereas it was shifted toward positive values with KCI electrodes. The glycinergic blocker strychnine, bath-applied to segments L3/L5, blocked the inhibitory drive without affecting the rhythmic activity, whereas it disrupted the locomotor-like activity when bathapplied to segments Ll/L2. The inhibitory part of the drive was more sensitive than the excitatory part to changes in the membrane potential. The excitatory phase was mixed and consisted of an NMDA and a non-NMDA component, which were sensitive to 2-amino-Sphosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione, respectively. It was concluded that the locomotor network located in segments Ll/L2 sends a biphasic projection to the various groups of motoneurons located along the lumbar spinal cord.Key words: electrophysiology; spinal cord; locomotion; motoneuron drive; glycine; excitatory amino acids During locomotor activity in mammals, the motoneurons are rhythmically depolarized and produce phasic bursts of action potentials which, in turn, elicit muscle contractions and limb movements. Schematically, two main components located at the lumbar spinal level can be described to take part in these motor rhythm generation processes: (1) the premotoneuronal locomotor spinal network, which is also called the central pattern generator (CPG); and (2) the motoneurons onto which all of the integrated information converges (Grillner, 1981). Although a considerable amount of data has been collected on the synaptic mechanisms responsible for this rhythmic behavior (for review, see Jordan, 1983Jordan, , 1991 Shefshick and Jordan, 1985;Perret, 1986;Roberts et al., 1986;Grillner and Matsushima, 1991), one question still remains regarding the relative contributions of these various elements, i.e., those of the premotoneuronal network on the one hand and the output motoneuronal compartment on the other hand. This gap in our knowledge has been attributable mainly to technical limitations that made it impossible to study these two elements separately. Using an in vitro isolated brainstemispinal cord preparation of newborn rat, we recent...

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Section: Lumbar Spinal Cordmentioning

confidence: 99%

The synaptic drive from the spinal locomotor network to motoneurons in the newborn rat

1996

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“…Although species differences cannot be completely excluded, examination of this study shows that it was done using CNQX as a specific blocker of AMPA receptors. CNQX has been widely described as being also an antagonist at NMDA-Rs, in part by competing with glycine at its modulatory site (Birch et al, 1988;Harris and Miller, 1989;Kessler et al, 1989;Pellegrini-Giampietro et al, 1989;Lester and Jahr, 1990;Mead and Stephens, 1999) and also with glutamate at its binding site (Lester and Jahr, 1990). In contrast, NBQX has no effect on NMDA currents (Sheardown et al, 1990).…”

Section: Cnqx Partly Blocks the Nmda-mediated Cf-epscmentioning

confidence: 99%

NMDA Receptor Contribution to the Climbing Fiber Response in the Adult Mouse Purkinje Cell

Piochon¹,

Irinopoulou²,

Brusciano³

et al. 2007

J. Neurosci.

109

100

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“…6-cyano-7-nitroquinoxaline-2.3-dione (CNQX, 10/tM) to block non-NMDA receptors (Blake, Brown & Collingridge, 1988;Honore, Davies, Drejer, Fletcher, Jacobsen, Lodge & Nielsen, 1988) and glycine (10 /tM) to ensure saturation of the glycine binding sites of NMDA receptors (Thomson, Walker & Flynn, 1989) and to increase the selectivity of CNQX to the non-NMDA receptors (Birch, Grossmann & Hayes, 1988 (Kostyuk. Krishtal & Pidoplichko, 1975;Kay, Miles & Wong, 1986), thus improving space clamp.…”

Section: Solutions and Drugsmentioning

confidence: 99%

Kinetic properties of NMDA receptor‐mediated synaptic currents in rat hippocampal pyramidal cells versus interneurones.

Perouansky

Yaari

1993

The Journal of Physiology

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4. In saline containing 1 mM Mg2+, the peak current-voltage (I-V) relationship of NMDA EPSCs in PCs and INs showed an area of negative slope conductance at voltages more negative than -20 to -30 mV. In nominally Mg2+-free saline, the peak I-V relation was linear over a much wider voltage range in both cell types.5. The 10-90 % rise times of NMDA EPSCs at -60 mV ranged from 4-5 to 16 ms in PCs (mean 8-7 ms; n = 25) and in M-INs (mean 9-1 ms; n = 10). Their decay could be best fitted with the sum of two exponentials. The 6. The time course of NMDA EPSCs in OA-INs (n = 37) was considerably more variable. In 18 9 % of the cells the rise times were in the ordinary range (4 5-10 nms: mean 6 9 ms) and the decay was biexponential (mean Tf and Ts8 49 and 212 ms: mean Af and As, -76'3 and -137'2 pA, respectively). In 73% of OA-INs the rise times were very slow (18-53 ms: mean 31-2 ms) and decayed monoexponentially (mean time constant 217 2 ms). The remaining 8% had rise times in the ordinary range (10-14 ms: mean 117 ms) but decayed as a single exponential (mean time constant 226 ms).7. Changes in holding voltage had no systematic effect on rise time and decay of ordinary and slow NMDA EPSCs.8. Neither changing the site of stimulation, nor modulating the amount of glutamate release by varying stimulus intensity, lowering extracellular Caa2+ or adding Cd21 to the saline, affected the rise time or the decay of slow NMDA EPSCs.9. We conclude that PCs and INs in area CAI of the rat hippocampus express NMDA EPSCs with different kinetic characteristics. NMDA EPSCs in the majority of OA-INs display unusually slow rise times.

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6,7-Dinitro-quinoxaline-2,3-dion and 6-nitro,7-cyano-quinoxaline-2,3-dion antagonise responses to NMDA in the rat spinal cord via an action at the strychnine-insensitive glycine receptor

Cited by 193 publications

References 6 publications

The synaptic drive from the spinal locomotor network to motoneurons in the newborn rat

The synaptic drive from the spinal locomotor network to motoneurons in the newborn rat

NMDA Receptor Contribution to the Climbing Fiber Response in the Adult Mouse Purkinje Cell

Kinetic properties of NMDA receptor‐mediated synaptic currents in rat hippocampal pyramidal cells versus interneurones.

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