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M Ariel

Publications and source records attributed to M Ariel.

At least 55 records · Page 3Linked to original sources
PubMed1988

Analysis of vertebrate eye movements following intravitreal drug injections. II. Spontaneous nystagmus induced by picrotoxin is mediated subcortically.

1. Eye movements were observed following an injection of picrotoxin, a GABA antagonist, into the vitreous of one eye. A spontaneous nystagmus was observed in cats, rabbits, and turtles, even in total darkness, with slow-phase eye movements in the temporal-to-nasal direction for the injected eye. 2. During visual stimulation by a horizontal drifting pattern, injected eyes moved in the temporal-to-nasal direction, irrespective of stimulus direction. In cats, however, the nystagmus was usually slower when the injected eye viewed nasal-to-temporal motion (opposite to the direction of the spontaneous nystagmus). The spontaneous nystagmus could be halted or even reversed by allowing cats to view motion opposite to the direction of the nystagmus with the uninjected eye alone. The nystagmus could not be overridden in this fashion in rabbits or turtles. 3. The nystagmus induced by picrotoxin could also be modified by vestibular stimulation. When cats were placed on their sides, the spontaneous horizontal nystagmus often decreased and spontaneous vertical nystagmus with upward slow phase movements occurred. During sinusoidal horizontal vestibular stimulation, the horizontal nystagmus due to picrotoxin added to the vestibuloocular reflex as a velocity offset in the temporal-to-nasal direction. 4. Following bilateral ablation of the cat visual cortex, picrotoxin's effect became even more pronounced than before the ablation. Therefore, at least some picrotoxin-sensitive cells can use subcortical pathways, perhaps to the accessory optic nuclei. The visual cortex, which also processes directional information, may be able to compensate for changes in retinal processing induced by picrotoxin in intact animals. 5. This study demonstrates the importance of retinal GABA in the control of eye stability. As GABA is known to be responsible for null direction inhibition of directionally sensitive retinal ganglion cells, these results suggest that the output of these cells may be critical for the normal functioning of central optokinetic pathways, even in the absence of visual cortex.

Animals↗
PubMed1986

N-methyl D-aspartate acts as an antagonist of the photoreceptor transmitter in the carp retina.

Glutamate, aspartate, and their agonists, kainate, quisqualate, cysteine sulfinate and N-methyl-D-aspartate (NMDA), were applied to the isolated carp retina while recording from horizontal cells. All these agents, except NMDA, depolarized horizontal cells membrane and reduced responses to light, thus mimicking the effect of the endogenous photoreceptor transmitter. Application of NMDA, on the other hand, caused a membrane hyperpolarization of horizontal cells in the dark, an effect different from its depolarizing effect as observed elsewhere in the central nervous system. NMDA also reduced or blocked the light responses of these cells as well as the depolarizing responses to applications of glutamate, aspartate or kainate. Effects of NMDA on the spectral properties of the horizontal cell responses were identical to the effects of the acidic amino acid receptor antagonists alpha-methyl glutamate, and alpha-amino adipate. Thus, NMDA appears to act as a weak antagonist to the photoreceptor transmitter, whose receptors on the horizontal cell membrane interact with a glutamate-like substance but appear atypical of glutamate receptors described elsewhere in the brain.

Animals↗
PubMed1985

Neurotransmitter inputs to directionally sensitive turtle retinal ganglion cells.

Synaptic drugs were superfused into turtle eyecup preparation while recording extracellularly from directionally sensitive (DS) retinal ganglion cells. As in previous experiments in intact rabbit retina, both picrotoxin (a GABA antagonist) and physostigmine [an acetylcholine (ACh) potentiator] reduced or eliminated the directional selectivity of these cells. These drug effects occurred at micromolar concentrations and were long lasting. Superfusion of ACh caused excitation, and GABA caused inhibition of the spike activity of these DS cells. In some experiments, the ganglion cell was isolated from its presynaptic inputs by perfusing with a low-Ca2+/EGTA perfusate, which blocked synaptic transmission but did not suppress spike firing. During this synaptic block, ACh still caused spontaneous spike firing, and GABA was able to suppress the ACh-induced spike activity. Strychnine slightly increased the spontaneous activity of DS ganglion cells and reduced their response to light. Glycine and taurine were equally effective in totally suppressing spike activity, and strychnine blocked this inhibition by both agents. However, these inhibitory effects may be transynaptic because glycine did not suppress ACh-induced excitation during synaptic block. Superfusion of micromolar concentrations of methionine enkephalin and [D-Ala2]methionine enkephalinamide occasionally caused small increases in the light responses of DS cells, whereas naloxone, a broad-spectrum opiate antagonist, moderately decreased light responsiveness. Because naloxone had no effect on these cell's directional tuning, the opiate system is probably not involved in the mechanism of directional sensitivity. Based on the effects of these transmitter candidates and their antagonists, a possible site fo DS subunits may be the ACh and GABA receptors on the membrane of DS ganglion cells. ACh provides light-evoked excitation that may, when potentiated by physostigmine, overcome asymmetric GABA inhibition. Although the role of glycine in directional sensitivity is small, it may be responsible for regulating presynaptic excitatory pathways leading to the DS ganglion cells.

Animals↗
PubMed1985

Effects of acidic amino acid antagonists upon the spectral properties of carp horizontal cells: circuitry of the outer retina.

The acidic amino acid receptor antagonists, alpha-methylglutamate and alpha-aminoadipate, were applied to the carp retina to study their effects upon the spectral properties of horizontal cells and to elucidate the synaptic connections between horizontal cells and cones. Application of these antagonists strongly hyperpolarized the L-type cone horizontal cells and reduced the responses of these horizontal cells to red light more than to blue light. Application of Co2+ ions to the retina, a procedure which decreases transmitter release, also hyperpolarized the L-type cone horizontal cells but reduced the response of these horizontal cells to red and blue lights equally. These results suggest that red- or long wavelength-sensitive cones release a different transmitter onto L-type cone horizontal cells than do short wavelength-sensitive cones. Application of the acidic amino acid antagonists also revealed details of the feedback pathway from L-type cone horizontal cells to cones. Previous studies have shown that feedback varies directly with stimulus size and that the effects of feedback on the responses of cones are observed as a transient waveform at response onset (a large, hyperpolarizing potential that is quickly followed by a smaller plateau potential). Application of the acidic amino acid antagonists at a dose which partially hyperpolarized the horizontal cells selectively enhanced the response of the cells to blue lights, when full field, and not spot, stimuli were used. The antagonists also eliminated the transient at response onset. These findings are consistent with the presence of a feedback pathway from L-type cone horizontal cells to short wavelength cones but not to long (red-sensitive) cones.

2-Aminoadipic Acid↗
PubMed1984

On the sensitivity of H1 horizontal cells of the carp retina to glutamate, aspartate and their agonists.

Threshold concentrations for L-glutamate, L-aspartate and their agonists, kainate, quisqualate and N-methyl-D,L-aspartate, were determined for horizontal cells of the intact carp retina and horizontal cells that were enzymatically isolated and maintained in culture. Our results indicate that uptake or other mechanisms decrease the apparent sensitivity of these cells in the intact retina to L-glutamate by 25-200 times. Our findings also suggest that L-glutamate is more likely a photoreceptor transmitter than L-aspartate.

Animals↗
PubMed1983

Rhythmicity in rabbit retinal ganglion cell responses.

An interesting pattern of rhythmic spike bursts was observed in the light responses of rabbit retinal ganglion cells when using a fast time scale. This rhythmicity was found in all ganglion cell types tested in all parts of the retina. The presence and extent of rhythmicity was related to the intensity, size and shape of the light stimulus. The best stimulus extended into the receptive field surround yet still evoked a strong response from the center. We suggest that rhythmicity results from time delays in the inhibitory interactions between central and surround pathways to the ganglion cells.

Action Potentials↗
PubMed1983

Effects of 6-hydroxydopamine on visual deprivation in the kitten striate cortex.

We tested the effects of 6-hydroxydopamine (6-OHDA) on two forms of visual deprivation--monocular and directional deprivation. In normal kittens monocular deprivation leads to a change in the ocular dominance histogram recorded from the visual cortex, and directional deprivation leads to a change in the percentage of directionally sensitive cells responding to the appropriate direction of movement. 6-OHDA was infused into the occipital cortex prior to the peak of the critical period for the effects of visual deprivation. In agreement with the results of Kasamatsu et al. (Kasamatsu, T., and J. D. Pettigrew (1979) J. Comp. Neurol. 185: 139-162; Kasamatsu, T., J. D. Pettigrew, and M. Ary (1979) J. Comp. Neurol. 185: 163-182), suture of one eye (monocular deprivation) after the 6-OHDA treatment did not lead to a shift in ocular dominance in the area of striate cortex infused. Moreover, rearing kittens in an environment continually moving past them in one direction (directional deprivation) did not lead to a change in the percentage of cells preferring movement in that direction. In both rearing procedures the 6-OHDA did not make the cells in the cortex nonspecific, compared to cells recorded from the cortex of animals reared similarly but without infusion of 6-OHDA. Monocular and directional deprivation are forms of visual deprivation with different critical periods, probably involving different synapses. Therefore, the effect of 6-OHDA on visual deprivation is a general one, involving more than one kind of visual deprivation. In both cases 6-OHDA abolishes the plasticity of the visual cortex.

Animals↗
PubMed1982

Effect of insulin on folic-acid transport in cultured fibroblasts.

Uptake of folic acid was measured in secondary cultures of skin fibroblasts from fetal rats. The cultures were made quiescent by 24 hours preincubation in medium containing 1% serum and subsequent 3 hours preincubation in phosphate buffered saline. The uptake of 3H-folic acid was linear with time during 15 seconds and reached a plateau level at 2-3 minutes. There was no further increase in the intracellular radioactivity until the end of the experiments at 10 minutes. The uptake of folic acid in fibroblasts was not concentrative and proceeded until equilibration with the extracellular concentration. Intracellular metabolic conversion of folic acid was not significant during the time of experiments (up to 10 minutes). Insulin caused a two-fold increase in the initial rate of folate uptake as determined from the 15 second uptake values. The dose response curves for the insulin effect showed that 85% of the maximal effect was exerted by 1 microM insulin. A lag period of 7-10 minutes was observed after the addition of insulin and before the effect on folic acid uptake was manifested. Thereafter the effect increased with the time of preincubation with insulin. The concentration dependence of folate uptake yielded non homogeneous curves. At low concentrations of substrate, saturable components were observed while at high concentrations (above 5 X 10(-6) M) a linear component was observed. Insulin increased the slope of the linear component and the Vmax of the saturable component while the Km remained unaltered.

Animals↗
PubMed1982

Effects of estradiol on uptake of folate in isolated intestinal epithelial cells.

Estradiol 17 beta caused significant changes in the time course of 3H-folate uptake into isolated chick-intestinal epithelial cells. The radioactivity within the cells initially increased reaching a level of 1.5-2 times that of the control thereafter decreased to somewhat below the control levels. These changes were prevented by sodium azide but not by inhibitors of protein synthesis.

Animals↗
PubMed1982

Effects of cholinergic drugs on receptive field properties of rabbit retinal ganglion cells.

1. Retinal ganglion cells were recorded extracellularly from the rabbit's eye in situ to study the effects of cholinergic drugs on receptive field properties. Physostigmine, an acetylcholinesterase inhibitor, and nicotine increased the spontaneous activity of nearly all retinal ganglion cell types. The effectiveness of physostigmine was roughly correlated with the neurone's inherent level of spontaneous activity. Brisk cells, having high rates of spontaneous firing, showed large increases in their maintained discharge, whereas sluggish cells, with few or no spontaneous spikes, showed small and sometimes transient increases in spontaneous activity during physostigmine.2. The sensitivity of ganglion cells to spots of optimal size and position did not change substantially during the infusion of physostigmine. However, the responsiveness to light (number of spikes per stimulus above the spontaneous level) increased. This effect occurred with sluggish and more complex cells, rarely with brisk cells.3. Another effect of physostigmine on sluggish and more complex cells was to make these cells ;on-off'. The additional response to the inappropriate change in contrast had a long latency and lacked an initial transient burst.4. Complex receptive field properties such as orientation sensitivity, radial grating inhibition, speed tuning and size specificity were also examined. These inhibitory properties were still present during infusion of physostigmine and, in most cases, the trigger feature of each cell type remained.5. These results are consistent with pharmacological results on ACh release from the retina. There appear to be two types of release of ACh, having their most powerful influences on separate classes of cells. One release (transient), occurs at light onset and offset and acts primarily on sluggish and more complex ganglion cells; the other release (tonic) is not light-modulated and acts primarily on brisk cells. A wiring diagram for the ACh cells is suggested.

Acetylcholine↗
PubMed1982

Pharmacological analysis of directionally sensitive rabbit retinal ganglion cells.

1. Cholinergic drugs were infused into the retinal circulation of the rabbit while we analysed the receptive field properties of directionally sensitive retinal ganglion cells. Physostigmine eliminated the trigger feature, directional specificity, of both types (on-centre and on-off) of these cells. In this respect the action of physostigmine (an ACh potentiator) was very like that of picrotoxin (a GABA antagonist). Therefore, a detailed analysis of the receptive field properties of directionally sensitive ganglion cells was made to analyse the effects of physostigmine and picrotoxin.2. Size specificity and radial grating inhibition were not abolished by physostigmine, but were often affected by picrotoxin. The optimal velocity in the preferred direction (as measured by maximum firing frequency) was not much changed by physostigmine, but was higher during infusion of picrotoxin. Infusion of nicotine, a depolarizing ACh agonist which increases the activity of retinal ganglion cells, revealed the presence of inhibition to movement in the null direction. The null direction response during picrotoxin started slightly later than this inhibition. The null direction response during physostigmine was weaker and started later still. Mecamylamine and dihydro-beta-erythroidine, nicrotinic receptor antagonists, totally blocked the effect of physostigmine and reduced the control light response by about half.3. From this analysis, it appears that on-off ACh release onto directionally sensitive cells provides a substantial excitation which, when potentiated by physostigmine, overcomes or outlasts the null direction GABA inhibition within the receptive field. The spatial extent of GABA inhibition is asymmetric to and larger than the spatial extent of ACh excitation. Similar pathways appear to be involved in both the on-centre and on-off directionally sensitive ganglion cells, yet the on-centre cell pathway may receive an additional input which suppresses the ACh excitation at light offset. Possible schemes for the cellular mechanism of directional sensitivity are discussed in light of these results and recent anatomical and pharmacological findings.

Acetylcholine↗
PubMed1982

Physiological and enzymatic properties of a thymidine-requiring Pediococcus cerevisiae mutant.

We describe the isolation and characterization of a Pediococcus cerevisiae thymidine-requiring mutant and its thymidine-independent revertant. The mutant strain lacked thymidylate synthetase activity and had an absolute requirement for low concentrations (2 micrograms/ml) of thymidine in addition to a requirement for N-5-formyl tetrahydrofolic acid (folinate). Even at high concentrations (up to 500 micrograms/ml), thymine could not replace thymidine. In contrast to its wild-type parent, which grows only on folinate, the thymidine-requiring mutant (Thy- Fol+) was able to take up and grow on picogram quantities of unreduced folic acid. When both strains were grown on folinate, the Thy- Fol+ strain was at least 10(3)-fold more resistant to the folic acid analogs aminopterin and methotrexate than the wild-type strain. On the other hand, when grown on folic acid, the Thy- Fol+ strain was as sensitive to the folic acid analogs as the Thy+ Fol+ strain and was 10(2)-fold more sensitive than the wild-type strain grown on folinate. The thymidine-independent revertant (Thy+ Fol+) regained the wild-type level of thymidylate synthetase activity, but maintained the ability to take up and grow on unreduced folic acid like its Thy- Fol+ parent.

Aminopterin↗
PubMed1982

Effect of phenytoin on folic acid uptake in isolated intestinal epithelial cells.

The anticonvulsant drug phenytoin was found to inhibit the uptake of folic acid into isolated chick intestinal epithelial cells. At a concentration of 100 micrograms/ml the drug inhibited the cellular accumulation of folic acid by 60%. The efflux of folic acid from preloaded cells was not affected by the drug. The inhibition was observed at an acidic pH of 5.8 and at a neutral pH of 7.4. Both the Na+-dependent and the Na+-independent components of folate uptake were inhibited. Phenytoin had no effect on the uptake of the glucose analog 3-O-methylglucose. Thus it was concluded that the effect of phenytoin on folate uptake was not due to changes in Na+ fluxes, concentration gradients or energy metabolism, and suggested instead a direct effect on the folic acid uptake system.

Animals↗
PubMed1981

On the mechanism of folate transport in isolated intestinal epithelial cells.

The mechanism of folic acid (FA) uptake was studied in isolated intestinal epithelial cells prepared from 2- to 6-wk-old chicks. The cells accumulated FA, reaching a level of three- to fivefold that at equilibrium. In the presence of the metabolic inhibitors, NaN3 or KCN, FA was taken up only until equilibration while accumulation of FA was inhibited. Addition of these inhibitors at a steady state of FA accumulation caused a release of intracellular FA. The kinetics of FA uptake were found to be saturable (Km = 3.5 x 10(-5) M), indicating a carrier-mediated mechanism. The steady-state level of FA accumulation was higher as the concentration of NA+ in the medium increased from 0 to 120 mM. This stimulation of FA uptake by Na+ was not due to the stimulation of glucose uptake, because in experiments carried out in the presence of phlorizin, a glucose-transport inhibitor, FA accumulation was not diminished. It is suggested that FA is taken up by a Na+-coupled transport system.

Animals↗