6-cyano-7-nitroquinoxaline-2-3-dione and 2-3-piperidinedicarboxylic-acid

The electroretinogram is a widely used objective measure of visual function. The best characterised feature of the full-field dark-adapted flash ERG, is the earliest corneal negativity, the a-wave, which primarily reflects photoreceptoral responses. However, recent studies in humans and primates show that there are post-receptoral contributions to the a-wave. It is not clear if such contributions exist in the rat a-wave. We consider this issue in the rat a-wave, using intravitreal application of pharmacological agents that isolate post-receptoral ON-pathways and OFF-pathways. In anaesthetised adult long Evans rats, we show that the ON-pathway (2-amino-4-phosphonobutyric acid, APB sensitive) makes negligible contribution to the a-wave. In contrast, CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) or PDA (cis-piperidine-2,3-dicarboxylic acid) sensitive mechanisms modify the a-wave in two ways. First, for bright luminous energies, OFF-pathway inhibition (CNQX or PDA) results in a 22% reduction to the early phase of the leading edge of the a-wave up to 14 ms. Second, OFF-pathway inhibition removed a corneal negativity that resides between the a-wave trough and the b-wave onset.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Aminobutyrates; Animals; Dark Adaptation; Electroretinography; Intravitreal Injections; Night Vision; Pipecolic Acids; Rats; Rats, Long-Evans; Retinal Rod Photoreceptor Cells

The purpose of this study was to examine inner-retinal contributions to the photopic sinusoidal flicker ERG. ERGs were recorded from 5 anesthetized monkeys to sinusoidally modulated (100%, 0.5-120 Hz) red full field flicker at Lmean of 3.2 log phot td on a rod saturating blue background (3.7 log scot td; 3.0 log phot td) before and after intravitreal injections of tetrodotoxin (TTX) to block Na+-dependent spikes of retinal ganglion and amacrine cells, followed by N-methyl-D-aspartate (NMDLA) to suppress all activity of these cells. Recordings also were made after blocking bipolar (and horizontal) cell responses with L-2-amino-4-phosphonobutyric acid (APB) and 2-cis-piperidine-2,3-dicarboxylic acid (PDA) or 6-cyano-nitroquinoxaline-2,3-dione (CNQX). Control fundamental (F1) and second harmonic (F2) amplitudes were large and variable at temporal frequencies up to 2 Hz. At higher frequencies, Fl amplitude was minimal with a phase step at a frequency between 13 and 19 Hz and maximal at 27-33 Hz. F2 was minimal at 2-3 Hz and maximal at 6-8 Hz, again with a phase step near the minimum. TTX, or NMDLA, produced small changes in Fl that shifted the amplitude minimum to a lower and the maximum to a higher frequency. In contrast, F2 was more strongly affected; both the amplitude minimum (and phase step) and maximum were greatly attenuated, leaving a moderate response from 0.5 to 8 Hz, which then declined as frequency was increased to 30 HZ. After APB and PDA or CNQX, F1 decreased continuously with increasing frequency and F2 was generally much smaller. The nearly linear F1 phase plotwas consistent with the presence of a single mechanism (i.e. photoreceptors). Inner-retinal neurons contribute to the photopic sinusoidal flicker ERG. Whereas for F1, inner-retinal contributions are small relative to those from bipolar cells; for F2, they are equal or greater between 2and 16 Hz.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Aminobutyrates; Animals; Electroretinography; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Female; Light; Macaca mulatta; Male; N-Methylaspartate; Photic Stimulation; Photoreceptor Cells; Pipecolic Acids; Retina; Tetrodotoxin

1. Climbing fibre-mediated excitatory postsynaptic potentials (CF-EPSPs) or currents (CF-EPSCs) were recorded from Purkinje cells in rat cerebellar slices using the whole-cell recording technique. 2. Climbing fibre responses displayed prominent paired-pulse depression (PPD). In the current-clamp recording mode, PPD resulted in a decreased number of spikelets in the second complex spike of the pair, and depression of the after-depolarization and after-hyperpolarization. 3. The mechanism of PPD was examined under voltage clamp. Manipulations that reduce transmitter release significantly affected PPD. These included lowering extracellular Ca2+ concentration and bath application of baclofen or adenosine. 4. Changing the number of stimulated climbing fibres, equivalent to changing the number of release sites, had no effect on PPD. 5. Selective manipulations of postsynaptic responsiveness had no effect on PPD. These included partial blockade of CF-EPSCs by a non-NMDA receptor antagonist, 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), and changing the holding potential. 6. A rapidly dissociating AMPA receptor antagonist, 2,3-cis-piperidine dicarboxylic acid, inhibited the second CF-EPSC of the pair proportionately more than the first, suggesting that presynaptic release by the second pulse is decreased. 7. PPD at interstimulus intervals of 50 ms or longer (up to 3000 ms) was not significantly affected by manipulations that change postsynaptic glutamate receptor desensitization. 8. Blockade of metabotropic glutamate, GABAB and adenosine receptors had no effect on PPD, suggesting that presynaptic autoreceptors do not contribute to PPD. 9. These results indicate that decreased transmitter release is a major cause of PPD at cerebellar climbing fibre-Purkinje cell synapses.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Action Potentials; Adenosine; Afferent Pathways; Animals; Baclofen; Calcium; Cerebellum; Diazoxide; Electric Conductivity; Electric Stimulation; Electrophysiology; Evoked Potentials; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Extracellular Space; GABA Agonists; GABA Antagonists; Nerve Fibers; Neurons; Neurotransmitter Agents; Pipecolic Acids; Presynaptic Terminals; Purinergic P1 Receptor Antagonists; Purkinje Cells; Rats; Rats, Wistar; Receptors, AMPA; Receptors, GABA-B; Receptors, Glutamate; Synapses; Synaptic Transmission; Vasodilator Agents

Effects of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 2-amino-4-phosphonobutyrate (APB), cis-2,3-piperidine dicarboxylic acid (PDA), and kynurenate (KYN) on the depolarizing actions of glutamate and kainate on horizontal cells (HCs) were studied in the larval tiger salamander retina. APB, PDA, and KYN hyperpolarized the HCs, but they failed to block either the actions of glutamate and kainate, or the HC light responses. APB and PDA did not cause membrane polarizations in either rods or cones, suggesting that the HC hyperpolarizations were not mediated by presynaptic actions of these compounds. CNQX, the newly synthesized non-NMDA (N-Methyl-D-Aspartate) receptor antagonist, blocked the HC light responses and the action of kainate, but not that of glutamate. These results suggest that the synaptic receptors in the tiger salamander HCs are probably non-NMDA although extra-synaptic NMDA receptors may exist in these cells.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Aminobutyrates; Animals; Glutamates; Glutamic Acid; Kainic Acid; Kynurenic Acid; Light; Membrane Potentials; Photoreceptor Cells; Pipecolic Acids; Quinoxalines; Receptors, Glutamate; Receptors, Kainic Acid; Receptors, Neurotransmitter; Retina; Urodela