Biomedical subjects

M Ariel

Publications and source records attributed to M Ariel.

At least 19 recordsLinked to original sources

PubMed1992

A "beat-to-beat" interval generator for optokinetic nystagmus.

An analysis of optokinetic responses was used to derive an iterative model that reproduces the duration of nystagmus slow phases and eye position control during optokinetic nystagmus. Optokinetic nystagmus was recorded with magnetic search coils from red-eared turtles (Pseudemys scripta elegans) during monocular, random dot pattern stimulation at constant velocities ranging from 0.25-63 degrees/s. The beat-to-beat behavior of slow phase durations was consistent with the existence of an underlying neural clock, termed the basic interval generator, that is based on an integrate-to-fire neuron model. This hypothetical basic interval generator produces an interval that is the product of the duration of the previous interval and a mean 1 truncated normal variate with variance sigma 2. Data analyses indicated that the initial value of the interval generator during a period of nystagmus, termed tau 0, is proportional to the inverse square root of slow phase eye velocity. Further, if the eye was deviated in the slow phase direction (re mean eye position) when the slow phase began, the slow phase duration was consistent with a single cycle of the basic interval generator. However, if the eye was deviated in the fast phase direction, the distribution of the durations of the ensuing slow phases indicated that a proportion of the slow phases were produced by more than one cycle of the basic interval generator. This phenomenon is termed "skipping a beat" and occurs with probability Ps. Finally, the amplitude of fast phases behaved as a linear function of eye position at the fast phase onset and the product of tau 0 and slow phase eye velocity. A computer simulation reproduced the observed distribution of slow phase durations, the proportion of fast phases in the fast phase and slow phase directions and the distribution of eye positions at the onset and end of fast phases. This novel model suggests that both timing and eye position information contribute to the alternation of nystagmus fast and slow phases.

Animals↗

PubMed1992

Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line.

Methylation patterns of specific genes have been studied by polymerase chain reaction and found to undergo dynamic changes in the germ line and early embryo. Some CpG sites are methylated in sperm DNA and unmodified in mature oocytes, indicating that the parental genomes have differential methylation profiles. These differences, however, are erased by a series of early embryonic demethylation and postblastula remodification events, which serve to reestablish the basic adult methylation pattern prior to organogenesis. During gametogenesis, all of these sites are unmethylated in primordial germ cells but eventually become remodified by 18.5 days postcoitum in both males and females. The final methylation profile of the mature germ cells is then formed by a multistep process of site-specific demethylation events. These results form a basis for the understanding of the biochemical mechanisms and role of DNA methylation in embryonic development.

Animals↗

PubMed1992

Spontaneous nystagmus and gaze-holding ability in monkeys after intravitreal picrotoxin injections.

1. Eye movements were measured in three rhesus monkeys after monocular intravitreal injections of picrotoxin, a gamma-aminobutyric acid (GABA) antagonist. The effects of this drug were tested when the animals were in a completely dark room, when they performed a smooth pursuit task, and when they viewed either a stationary pattern or a full-field optokinetic pattern rotating horizontally. 2. Between 15 and 20 min after the injection, a sustained conjugate spontaneous nystagmus developed in the dark, with the slow-phase movement in the temporal-to-nasal direction with respect to the injected eye. Peak slow-phase velocity ranged from 15 to 45 degrees/s. The nystagmus persisted for at least 1 h but stopped by the next day. 3. In a well-lit room, the nystagmus was completely suppressed, even during monocular viewing with the injected eye. When the lights were turned off, the slow-phase velocity of the spontaneous nystagmus slowly increased to a steady-state level within 70-120 s. 4. Horizontal smooth pursuit eye movements to a 1 degree target light moving in front of the animal +/- 20 degrees to either side of center of gaze at constant speeds were normal. Target speeds ranging from 15 to 60 degrees/s for both monocular and binocular viewing conditions were used. Binocular and monocular optokinetic nystagmus (OKN) to a full-field drum rotating at a constant velocity (5-90 degrees/s) were also normal. The initial pursuit and steady-state components of OKN were measured, as well as the velocity-storage component (optokinetic after nystagmus, OKAN).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Methylation patterns of testis-specific genes.

The methylation patterns of genes expressed in the mouse male germ line have been examined. Int-1, Hox-2.1, and Prm-1, all of which contain 5' CpG islands, were found to be completely unmethylated at many sites in these domains, both in somatic tissues and in sperm DNA. Many other testis-specific genes have a similar structure and are probably also constitutively unmethylated. Pgk-2, a non-CpG-island gene, is similar to somatic tissue-specific genes in that it is highly methylated in nonexpressing cell types but undermethylated in pachytene spermatocytes and round spermatids, where it is actively transcribed. At later stages of spermatogenesis, however, the gene becomes remethylated and thus acquires the full modification pattern in sperm DNA. In all these cases, the sperm DNA that emerges from the testis does not contain any germ-line-specific unmethylated sites and thus carries the methylation pattern typical of that in somatic tissues.

Animals↗

PubMed1991

Effects of synaptic drugs on turtle optokinetic nystagmus and the spike responses of the basal optic nucleus.

Behavioral and electrophysiological measures were used to elucidate the retinal modulation of oculomotor control in the turtle. Eye movements were recorded following intravitreal applications of 2-amino-4-phosphonobutyrate (APB) and the GABA antagonists picrotoxin and bicuculline. Visual responses of single basal optic nucleus (BON) neurons of the accessory optic system were studied in parallel experiments. The effectiveness of APB, a glutamate analog thought to act selectively on the retinal ON pathway, was assessed independently by recording electroretinograms or ganglion cell activity. Injections of APB into the turtle's eye reduced or blocked the injected eye's ability to drive horizontal optokinetic nystagmus, as also observed in rabbit and cat (Knapp et al., 1988; Yucel et al., 1989). Single-unit recordings from the BON during APB superfusion (50-200 microM APB) of the contralateral retina demonstrated that these cells, which are direction-sensitive and respond to the offset of light flashes, have their responses to moving stimuli blocked by APB. During the APB effect, GABA antagonists were applied to the same eye. Although moderate doses of APB were sufficient to block optokinetic or BON light responses, the addition of GABA blockers still elicited a spontaneous temporal-to-nasal nystagmus (Ariel, 1989) or visually responsive yet direction-insensitive responses from BON cells (Schuerger et al., 1990). These results are discussed in terms of the retinal output to pathways involved in oculomotor control of optokinetic nystagmus.

Aminobutyrates↗

PubMed1991

Analysis of vertebrate eye movements following intravitreal drug injections. IV. Drug-induced eye movements are unyoked in the turtle.

1. Eye movements of awake turtles were measured from both eyes simultaneously using two search-coil contact lenses. Optokinetic nystagmus (OKN) was evoked by full field patterns moving horizontally at different stimulus velocities. Intravitreal injections of either bicuculline or 2-amino-4-phosphonobutyrate (APB) were then made into one eye, after which eye movements were again recorded under similar stimulus conditions. Several days later, eye movements were again recorded and recovery was observed. 2. The effects of these two synaptic drugs on the optokinetic responses of the injected eye were similar to those previously reported in turtles, rabbits, and decorticate cats. APB, which blocks the retinal ON pathways, completely blocked visually evoked responses to any stimulus direction or velocity presented to the injected eye. On the other hand, the uninjected eye was still responsive to optokinetic stimuli. This difference between the eyes is consistent with the nonconjugate nature of OKN in the turtle. 3. After bicuclline application, the injected eye displayed a spontaneous nystagmus with its slow phase in the temporal-to-nasal direction. The movements of the injected eye were independent of stimulus direction or a range of stimulus velocities. During that effect, the eye contralateral to the injection still responded to visual stimuli in a direction- and velocity-dependent manner. For example, if the uninjected eye was exposed to optokinetic stimuli moving temporal-to-nasal, both eyes would then move in their respective temporal-to-nasal directions. This nonconjugate ocular behavior is similar to that seen when each eye of a normal turtle was exposed to its temporal-to-nasal stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminobutyrates↗

PubMed1991

Electrophysiological evidence for a direct projection of direction-sensitive retinal ganglion cells to the turtle's accessory optic system.

1. The direct retinal input pathway to the basal optic nucleus (BON), the primary nucleus of the turtle accessory optic system, was characterized physiologically. We tested the hypothesis that directional information encoded in retinal ganglion cells can influence the BON via a direct pathway. Using an in vitro whole-brain, eyes-attached preparation, we demonstrated the directness of this pathway by 1) antidromic activation of retinal ganglion cells from the contralateral BON and 2) orthodromic activation of the BON from the contralateral optic nerve. 2. Of 72 physiologically classified retinal ganglion cells, 9 could be antidromically activated from the contralateral BON with low current (less than 200 micro A). Eight of these cells were direction-sensitive (DS). The ninth cell did not respond to visual stimulus movement. The antidromic latencies ranged from 2.2 to 6.1 ms with a mean of 3.8 ms. These latencies were quite consistent for each cell, having an average SD of 0.08 ms. Moreover, consistent responses could always be recorded at stimulation rates up to 100 Hz. 3. With current stimulation of the contralateral optic nerve, the orthodromic conduction latency of 17 BON single units ranged from 2.5 to 6.6 ms with a mean of 4.6 ms. These latencies were more variable for an individual cell, having an average SD of 0.3 ms. Responses to individual current pulses could never be consistently evoked at stimulation rates greater than 40 Hz. 4. DS responses were recorded in BON single units after the removal of the dorsal midbrain, including the optic tectum and pretectum as well as the telencephalon. Three of these cells were activated orthodromically by current stimulation delivered to the contralateral optic nerve. Thus directional information reaches the BON via a direct projection from the contralateral retina. 5. Visual response properties of DS retinal ganglion cells were compared with those of BON cells to examine the transformations that take place in the brain stem. Applying a limaçon model to the responses of both DS retinal ganglion cells and BON cells revealed that both types of cells have very similar direction tuning. However, the distribution of maximally responsive directions in the retina may differ from that of the BON. 6. Because DS retinal ganglion cells project directly to the BON, and because BON cells lose their direction sensitivity after retinal application of GABA antagonists, we conclude that the BON receives essential directional information directly from DS retinal ganglion cells. This directional information in the BON may represent a retinal slip error signal necessary for retinal image stabilization.

Animals↗

PubMed1990

Retinal direction-sensitive input to the accessory optic system: an in vitro approach with behavioral relevance.

Retinal application of gamma-aminobutyric acid (GABA) antagonists block direction-sensitive (DS) responses in turtle in two ways: (1) the selectivity of DS retinal ganglion cells in vitro, and (2) the eye's ability to track the direction of full field image motion. The experiments described below demonstrate that an important locus for retinal slip computation by the accessory optic system (AOS) occurs in the retina. Visual responses were measured physiologically and behaviorally from turtles which had their telencephalon removed. Physiological responses to visual field movement were recorded in the AOS using an in vitro brain preparation. DS responses of single cells were blocked by intravitreal application of bicuculline. The behavioral approach was to measure optokinetic nystagmus (OKN) in lesioned animals. OKN occurred in the absence of the telencephalon, yet was disrupted following an intravitreal injection of bicuculline. Thus, both experimental approaches showed that DS processing exists without the telencephalon, yet is disrupted by GABA antagonists applied to the retina.

Animals↗

PubMed1990

Independent eye movements in the turtle.

In order to evaluate the normal eye movements of the turtle, Pseudemys scripta elegans, the positions of each eye were recorded simultaneously using two search-coil contact lenses. Optokinetic nystagmus (OKN) was strikingly unyoked in this animal such that one eye's slow-phase velocity was substantially independent of that of the other eye. On the other hand, the fast-phase motions of both eyes occurred more or less in synchrony. An eye's slow-phase gain is primarily dependent on the direction and velocity of the stimulus to that eye. Using monocular stimuli, the highest mean gain (0.54 +/- 0.047; mean +/- standard error of mean) occurred using temporal-to-nasal movement at 2.5 deg/s. The mean OKN gain for nasal-to-temporal movement was only 0.13 +/- 0.015 at that velocity. Additionally, using the optimal monocular stimulus (temporal-to-nasal stimulation at 2.5 deg/s) only drove the occluded eye to move nasal-to-temporally at 0.085 deg/s, equivalent to a "gain" of only 0.034 +/- 0.011. The binocular OKN gain during rotational stimuli was higher than monocular gain, especially during nasal-to-temporal movement at high velocities. Also the difference in slow-phase eye velocity between the two eyes was smaller during binocular rotational stimuli. In contrast, when each eye simultaneously viewed its temporal-to-nasal stimulus at an equal velocity, two behaviors were observed. Often, OKN alternated between an animal's left eye and right eye. Occasionally, both eyes moved at equal but opposite velocities. These behavioral data provide a quantitative baseline to interpret the properties of the retinal slip information in the turtle's accessory optic system. Those properties are similar to the behavior of the turtle in that both are tuned to direction and velocity independently for each eye (Rosenberg & Ariel, 1990).

Animals↗

PubMed1990

Direction-selective responses of units in the dorsal terminal nucleus of cat following intravitreal injections of bicuculline.

Extracellular recordings from single units in the dorsal terminal nucleus (DTN) of the cat accessory optic system (AOS) were made before and after intravitreal injections of the GABA antagonist bicuculline methiodide (BMI). Direction-selective responses of DTN cells elicited through the contralateral, injected eye were abolished 7-12 h following the injection. For the concentrations tested, direction-selective responses through the contralateral (injected) eye did not recover within 26 h. Direction-selective responses through stimulation of the ipsilateral (uninjected) eye were also dramatically depressed for 1-9 h after contralateral eye injections. However, direction-selective responses through the ipsilateral eye eventually returned and were often more vigorous in the final stages. BMI injections into the ipsilateral eye failed to block direction-selective responses through the ipsilateral eye. The effects of intravitreal BMI on contralateral eye responses imply that DTN units receive input from direction-selective retinal ganglion cells. In addition, these results suggest that direction-selective input to the DTN from the visual cortex is independent of the retinal pathway. Using pharmacological methods described here, for the first time direction-selective responses of AOS units driven through the ipsilateral eye can be experimentally isolated.

Animals↗

PubMed1990

Visual-response properties of neurons in turtle basal optic nucleus in vitro.

1. The spike responses of 105 cells to visual-stimulus movement were analyzed in the turtle's basal optic nucleus (BON) in vitro in the absence of the telencephalon. All cells were direction sensitive (DS) and were driven solely by stimulation of the contralateral eye. These cells had large receptive fields and had vigorous responses to moving, textured patterns. Small moving spots generated only weak responses from these cells, as did the onset or offset of diffuse light flashes. 2. The direction tuning of BON cells was quite broad with most back and forth responses being DS. In fact, for 86% of the cells, there were seven to nine axes (out of 9 total, in 20 degrees increments) for which response to movement in one direction was at least twice that for the opposite direction. In instances where spontaneous activity was relatively high, a suppression of that spike firing was evident when the stimulus moved in directions opposite to preferred stimulus directions. 3. Cells preferring many different directions are found in the BON. More cells preferred inferior-temporal directed motion (49%), compared to superior-temporal (35%) and nasal stimuli (13%). 4. BON cells remained DS over 3 log units of velocity, with their strongest responses between 1 and 50 degrees/s. Responses were often non-DS for stimuli moving slower than 0.1 degrees/s. 5. The receptive fields of BON cells were large and occupied different parts of the retina. When different subregions of a receptive field were stimulated, the cell's directional tuning always remained the same as the full field direction tuning. 6. Thus, BON cells seem well-suited for the analysis of global, visual-field motion in any direction, performed by the accessory optic system. Other brain stem pathways necessary for optokinetic reflexes can be elucidated with the use of this whole-brain, eyes-attached in vitro preparation.

Action Potentials↗

PubMed1989

D-aspartate potentiates the effects of both L-aspartate and L-glutamate on carp horizontal cells.

L-Aspartate, L-glutamate and D-aspartate, alone or in combination, were applied by superfusion or by atomization to the isolated carp retina while recording from cone horizontal cells. Each of these agents when applied alone depolarized horizontal cells and reduced the size of their light responses, an action which mimics the effect of the endogenous photoreceptor transmitter. Application of D-aspartate in conjunction with either of the L-amino acids potentiated the effects the L-amino acids so that the threshold concentration was reduced by about five-fold, compared to when the L-amino acids were applied alone. The potentiating effect of D-aspartate occurred with all types of cone horizontal cells--both L- and C-types. Furthermore, the potentiating effect of D-aspartate occurred not only in the dark but also in the presence of bright light background or Co2+ ions, conditions during which the release of photoreceptor transmitter is reduced or blocked. D-Aspartate also potentiated the depolarizing effects of the acidic amino acid cysteine sulfinate. The potentiating effect of D-aspartate can be attributed to its action as an amino acid uptake blocker in the outer retina. Thus, these findings, in themselves, cannot eliminate L-aspartate, L-glutamate or cysteine sulfinate as candidates for the carp cone transmitter. However, other evidence, previously reported, strongly suggests that L-glutamate and not L-aspartate is the cone transmitter.

Animals↗

PubMed1989

Analysis of vertebrate eye movements following intravitreal drug injections. III. Spontaneous nystagmus is modulated by the GABAa receptor.

1. Turtle eye movements were recorded in response to horizontal motion of patterned stimuli and intravitreal injections of selective GABAergic drugs by using a contact lens search-coil technique. Similar to results from rabbit and cat, injection of picrotoxin into the turtle's eye results in a spontaneous horizontal nystagmus, with its slow-phase movement in a temporal-to-nasal direction with respect to the injected eye. In contrast, there were no prominent vertical eye movements in response to either horizontal optokinetic stimuli or drug injections. 2. Injections of bicuculline or bicuculline methyl iodide (BMI), which selectively block the GABAa receptor, had effects similar to those of picrotoxin. The GABAa agonist muscimol, on the other hand, blocked optokinetic nystagmus (OKN). Furthermore, combinations of these drugs demonstrated competitive interactions between the agonists and antagonists. 3. The threshold dose for the eye-movement effects of each drug was ascertained with the use of a radioactive calibration procedure. Tritiated inulin was injected into the vitreous. After 1 h, ocular components were assayed for radioactivity. Then, by the use of an estimate of vitreal/retinal dilution, the retinal concentrations of these threshold doses were calculated. The computed threshold retinal concentrations of the GABAa drugs were found to be in the low micromolar range. 4. These results are discussed in terms of the directionally sensitive (DS) processing which occurs in the retina, and the output of retinal DS cells to pathways involved in oculomotor control of retinal image stabilization. It is known that intravitreal application of picrotoxin makes DS retinal ganglion cells lose their selectivity for any one direction. Based on the effect of picrotoxin on OKN, it is argued that DS retinal cells provide a major input to oculomotor subsystems involved in the stabilization of gaze. Furthermore, these intravitreal drug effects on OKN are selective for GABAa drugs, suggesting that GABAa receptors play a major role in DS processing in the retina.

Animals↗

PubMed1988

Analysis of vertebrate eye movements following intravitreal drug injections. I. Blockade of retinal ON-cells by 2-amino-4-phosphonobutyrate eliminates optokinetic nystagmus.

1. Horizontal optokinetic nystagmus (OKN) was examined in alert rabbits and cats following intravitreal injection of 2-amino-4-phosphonobutyrate (APB), an agent which selectively blocks the light-responsiveness of retinal ON-cells while having little effect on OFF-cells. The retinal actions of APB were assessed independently by electroretinography. 2. In five rabbits, doses of APB sufficient to eliminate the b-wave of the electroretinogram reduced drastically the ability of the injected eye to drive OKN at all stimulus speeds tested (1-96 degrees/s). Impairment of OKN was apparent within minutes of the injection, remained maximal for several hours, and recovered completely in 1-7 days. OKN in response to stimulation of the uninjected eye alone remained qualitatively and quantitatively normal. 3. Following administration of APB, OKN in response to binocular stimulation displayed a directional asymmetry. Stimuli moving in the preferred (temporal-to-nasal) direction for the uninjected eye became more effective than stimuli moving in the opposite direction, indicating that the injected eye could no longer contribute to binocular OKN. 4. When rabbits viewed stationary stimuli through the APB-treated eye alone, episodes of slow (less than 1 degrees/s) ocular drift were observed, similar to the positional instability seen when rabbits are placed in darkness or when the retinal image is stablized artifically (12). 5. APB had little effect on OKN in normal cats. In two cats that had previously received large lesions of the visual cortex, however, APB eliminated the ability of the injected eye to drive monocular OKN. The extent of the impairment was similar to that seen in rabbits. Because the cortex is thought to contribute more to OKN in cats than in rabbits, this result suggests that the optokinetic pathways disrupted by APB project subcortically. 6. This study demonstrates that the integrity of retinal ON-cells is required to sustain normal OKN. The results are consistent with additional anatomic and physiological evidence suggesting that a particular subclass of retinal ganglion cells, the ON-direction-selective cells, may provide a crucial source of visual input to central optokinetic pathways.

Aminobutyrates↗

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↗