Norma Wioland

Antagonists of the putative inhibitory transmitter effects of taurine and gaba in the retina

Abstract Intravitreal injection of taurine or GABA produces a marked decrease of the b-wave amplitude in the chicken ERG. Strychnine abolishes the depressant action of taurine, but not that of GABA. On the contrary, picrotoxin abolishes the depressant action of GABA, but not that of taurine. Taurine and GABA seem to act as inhibitory transmitters in the retina; taurine could be responsible for a postsynaptic inhibition, whereas GABA appears to be responsible for a presynaptic one. The complex nature of the effects of these amino acids on the tectal-evoked responses indicates that these substances act at more than one retinal site. The role of taurine considered as an inhibitory transmitter, or as a modulator, is also discussed.

Effects of dl-α-amino adipic acid on Müller cells in frog and chicken retinae in vivo: Relation to ERG b wave, ganglion cell discharge and tectal evoked potentials

In both frog and chicken, an intravitreal injection of DL-alpha-amino-adipic acid, (DL-alpha aaa) provoked a progressive depression and eventually the disappearance of the ERG b wave that was concomitant with severe damage to the Müller cells without any apparent damage to retinal neurons. Ganglion cell discharges as well as tectal evoked potentials were still recorded, i.e. a visual message was still generated in the retina and transmitted to the optic tectum, when the Müller cells had been damaged to as to provoke an abolition of the ERG b-wave. The whole of the drug-induced effects proved to be reversible.

Electrooculographic and electroretinographic study in the chicken after dopamine and haloperidol

The implication of dopamine in the modulation of the standing potential of the eye was tested in the chicken through an indirect electrooculographic method and direct current electroretinogram (ERG) recording after haloperidol, a mixed D1-D2 antagonist. The standing potential of the eye was reduced within 15 min after intravitreal injection of the antagonist (150 μg). This effect is rapidly reversed by an application of dopamine. The fast oscillation was preserved but the light peak was either strongly reduced or abolished. The dark trough showed an apparently normal time course. The intensity-voltage function was studied for the various ERG components. After haloperidol the b-wave and the c-wave were strongly reduced, whereas the a-wave was little affected. Together with previous data obtained with intraocular injections of dopamine, our data suggest the involvement of dopamine in the modulation of the standing potential. They also support the hypothesis that the light peak, which is generated by a photoreceptor-pigment epithelium interaction, is influenced by dopamine or by a related substance. The modulatory effect could also be due to a balance between several neurotransmitter systems.

Dopamine and melatonin interactions in the intact chicken eye. Electrooculographic and biochemical study

Electrophysiological and biochemical techniques were used to investigate the interactions between dopamine (DA) and melatonin (MEL) in the intact chicken eye. Endogenous DA depletion induced by intraocular administration of alpha-methyl-para-tyrosine (alpha-MPT), a selective tyrosine hydroxylase inhibitor, decreases the transepithelial potential (TEP) of the retinal pigment epithelium and reduces the light peak (LP) recorded by an indirect electro-oculographic (EOG) method. An intraocular injection of MEL also reduces the TEP but does not reduce the LP. Retinal MEL is increased after endogenous DA depletion and a tight inverse correlation between DA and MEL contents was found. The present data, together with other findings support the hypothesis (1) that in the intact chicken eye, DA and MEL play respectively a role of light and dark signals on the TEP, and (2) that a balance between these two neurohormones may be responsible for the regulation of RPE events which are dependent on light-dark conditions.

On gabaergic mechanisms in the optokinetic nystagmus of the frog: Effects of bicuculline, allyglycine and SR 95103, a new GABA antagonist

In a monocular situation, an intravitreal injection of the GABA antagonists, bicuculline or SR 95103 provoked both the suppression of the optokinetic nystagmus (OKN) related to the injected eye and the appearance of a Nasal-Temporal (N-T) component in the OKN triggered by the contralateral non-injected eye (this N-T component being absent in control OKN). These two effects were added in a binocular condition. Similar results were obtained with L-C allylglycine which reduces the endogenous GABA level, but these effects were delayed when compared to those of GABA antagonists. All these data are roughly analogous to those previously obtained with picrotoxin (a non-competitive GABA antagonist) and thus confirm that GABA mechanisms are involved in the control of the frog OKN. Furthermore, SR 95103 acted in this model as a potent selective GABA antagonist, as has been demonstrated in another system.

Anisotropic inhibition in the receptive field surround of the frog retinal ganglion cells, evidenced by bicuculline and SR 95103, a new GABA antagonist

When GABA antagonists (picrotoxin, bicuculline methiodide and SR 95103) were intravitreally injected in the frog, they increased the number of spikes of transient retinal ganglion cells, as well as the duration of the response. Thus, the transient pattern of the response became more sustained. GABA antagonists also provoked a marked increase in the size of the receptive field, which might be due to the abolition of the inhibition exerted by the surround upon the centre of the field. In fact, a stimulus applied to the surround of the field simultaneously with one applied to the centre no longer provoked the reduction of the field area nor that of the number of spikes. These are effects which were always observed before drug injection. After picrotoxin injection, the enlarged field was concentric with the initial one, both angular diameters doubled, whereas after bicuculline or SR 95103, the enlarged field was not concentric with the initial one and only one diameter increased. Thus, GABA inhibition appears to be distributed according to an anisotropic spatial pattern. Whether this anisotropy might be an input for direction selectivity in the frog visual system is a topic of discussion. With respect to SR 95103, this compound proved to act like a selective GABA antagonist with long lasting effects.

Photopic c-wave in the chicken ERG: sensitivity to sodium azide, epinephrine, sodium iodate, barbiturates, and other general anesthetics

The c-wave recorded in the chicken electroretinogram proved to be a conetriggered component. The questions arose whether its reactivity to various specific drugs (sodium iodate, sodium azide, epinephrine, or barbiturates) were similar to those described for classic rod-triggered c-waves. We also tested the sensitivity of the chicken c-wave to various general anesthetics. Urethane was found to be the drug that best preserves the c-wave in electrophysiological recordings.

Is dopamine involved in the generation of the light peak in the intact chicken eye

The implication for dopamine (DA) in the modulation of the standing potential (SP) and the light peak (LP) was tested in intact chickens using an indirect EOG method. After an intravenous or intravitreal injection of DA, a transient, dose-dependent increase in the SP was observed. The LP, recorded after an intravenous injection, was preserved. But after an intravitreal injection, the LP was strongly reduced or even abolished depending on the dose of DA, whereas the photoreceptor response was unchanged. The data supports the hypothesis that the light peak, which is generated by a neural retina-pigment epithelium interaction, could be triggered by dopamine released at light onset from the inner retinal layers.

Electrooculographic study in the chicken after treatment with neurotoxin 6-hydroxydopamine

The implication of dopamine in the modulation of the standing potential of the eye was tested in the chicken by an indirect electrooculogram (EOG) method. After a single rapid systemic injection of dopamine, a transient dose-dependent increase in the EOG voltage was observed. EOG recordings during light and dark adaptation were performed after retinal dopamine depletion was induced by intraocular injections of the neurotoxin 6-hydroxydopamine (6-OHDA). The eyes were injected on two successive days with a mixture of 6-OHDA (50 μg), pargyline (a monoamine oxidase inhibitor), and ascorbate added as an antioxidant. Following this treatment EOG recordings were performed 1, 4, and 8 days after the second injection. The electrophysiological changes appeared most spectacular on the fourth day: an important increase in the EOG basal values as well as of the amplitude of the light peak and of the dark trough were observed. Substantial reduction in retinal concentration of dopamine was found in treated retinas. These unexpected electrophysiological data offer additional evidence for the involvement of a catecholamine in the generation of the light peak and the dark trough of the EOG.

Physiological effects of muscarinic vs nicotinic ACh antagonists upon ganglion cell activity in the frog retina.

The intravitreal administration of ACh agonists (eserine, carbachol, oxotremorine) or that of ACh muscarinic antagonists (scopolamine, atropine) provoked a reduction of the On-Off ganglion cell discharges. The agonists depressed the Off discharges more than the On discharges, while the ACh muscarinic antagonists depressed the On- more than the Off discharges. These drugs did not modify the ganglion cell receptive field area; thus, the muscarinic cholinergic system seems not to be involved in the spatial organization of the On-Off ganglion cells, but rather seems to play an important part in the separation of On and Off information channels. ACh nicotinic antagonists [hexamethonium, D-tubocurarine (D-TC), alpha-bungarotoxin (alpha-BGTX)] provoked an increase of the receptive field area of On-Off ganglion cells, this enlargement being due to the suppression of the inhibition normally exerted by the surround upon the centre of the field. Moreover D-TC and alpha-BGTX, but but hexamethonium, increased the number of ganglion cell discharges. These data are analogous to those obtained after administration of GABA antagonists and show that through nicotinic receptors, ACh seems to be involved in the spatial organization of the On-Off ganglion cell.