Nicole Bonaventure

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.

Glutamatergic separation of ON and OFF retinal channels: possible modulation by glycine and acetylcholine

When intravitreally injected into the frog in vivo, 2-amino-4-phosphonobutyrate (APB) and cis-2,3-piperidine dicarboxylic acid (PDA) showed opposite effects on ON and OFF retinal channels: APB abolished the ON responses in the electroretinogram and in ganglion cell activity, and increased OFF responses. At the same time the receptive field area was enlarged, and the inhibition exerted by the surround was suppressed. A cholinergic/glycinergic loop involving amacrine cells was suggested to be the pathway of the inhibitory ON input upon the OFF channel. PDA abolished the OFF responses in the ERG and in ganglion cell activity, while increasing the ON response in the ERG and decreasing the ganglion cell sensitivity at ON. The receptive field area was not modified, but the inhibition exerted by the surround was suppressed, probably by a blockade of horizontal cell glutamate receptors.

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.

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.

Unilateral pretectal microinjections of SR 95 531,a GABA A antagonist: effects on directional asymmetry of frog monocular OKN

SummaryMonocular eye movements have been studied in frogs using the search coil technique before and after unilateral microinjection of SR 95 531, a GABA A antagonist, into the pretectal nuclei contralateral to the open eye. Before injection, monocular, horizontal optokinetic nystagmus (OKN) in frogs, as in other lower vertebrates, displays a directional asymmetry: the stimulation in the T-N (temporo-nasal) direction is more efficient in evoking OKN than is stimulation in the N-T (naso-temporal) direction The N-T component is almost absent and displays only slow phases of very low speed. Unilateral SR 95 531 microinjection into the pretectum reversibly decreased the directional asymmetry of monocular horizontal OKN, by strongly increasing the N-T component slow phase velocity while the T-N slow phase velocity remained unchanged. These data show that SR 95 531 injected into the pretectum contralateral to the open eye reversibly decreased the inhibition upon the N-T component of monocular horizontal OKN, which suggests that a pretectal GABAergic system is involved in the directional asymmetry of monocular horizontal OKN in frogs.

Possible involvement of cholinergic and glycinergic amacrine cells in the inhibition exerted by the ON retinal channel on the OFF retinal channel

In the frog retina, the inhibition exerted by the ON channel on the OFF channel was evidenced by the increase in transient ganglion cell OFF responses, when the ON channel was blocked by 2-amino-4-phosphonobutyrate (APB). Intraocular administration of the neurotoxic choline analog ethylcholine mustard arizidinium ion (ECMA) also provoked an increase in the number of spikes of transient ganglion cell OFF responses, without suppressing the ON responses. APB, when administrated after ECMA, abolished the ON responses, but did not modify the OFF responses already increased by ECMA. Neurons located in the inner part of the inner nuclear layer were histologically altered by the toxin, and choline acetyltransferase activity was significantly depressed in ECMA-treated retinas. A double immunostaining experiment showed that amacrine cells containing glycine bear muscarinic binding sites. These results confirm the participation of cholinergic neurons in the inhibition exerted by the ON retinal channel on the OFF retinal channel, and suggest the involvement of a cholinergic/glycinergic loop of amacrine cells in this mechanism.

Directional asymmetry of the horizontal monocular head and eye optokinetic nystagmus: Effects of picrotoxin

Frog monocular eye and head optokinetic nystagmus (OKN) were studied by coil recordings after intravitreal administration of picrotoxin into the closed eye. Before injection, the frog displayed an OKN only for stimulations in the temporo-nasal (T-N) direction. The injection of picrotoxin provoked the appearance of a N-T component of the head and eye OKN: the slow phase velocity gain and the resetting fast phase frequency were strongly and significantly increased. Thus, picrotoxin abolished the directional asymmetry of head and eye OKN, indicating the involvement of GABAergic mechanisms in the inhibition of the N-T component of the monocular eye and head OKN. Picrotoxin administration had an additional effect on the monocular head OKN only, the performances (measured by the velocity gain and the frequency of resetting fast phases) were markedly increased for both directions of stimulation, suggesting an effect of the drug upon the motor output of head movements.