V&ion Res. Vol. 30, No. 4, pp. W-555, 1990 Printed in Great Britain. All rights reserved
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DIRECTIONAL ASYMMETRY OF THE HORIZONTAL MONOCULAR HEAD AND EYE OPTOKINETIC NYSTAGMUS: EFFECTS OF PICROTOXIN Y. H. Y&EL, B. JARDON,M.-S. KIM and N. BONAVENTIJRE* Dtpartement de Neurophysiologie et Biologic des Comportements, Centre de Neurochimic du CNRS, Strasbourg, France (Received 21 June 1989; in revised form 14 Augusr 1989) Abstract-Frog monocular aye and head optokinetic nystagmus (OKN) wara studiad by coil recordings aftex 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. Optokinetic nystagmus Frog
Eye movement
Head movement
iNTltODUC3ION
optokinetic nystagmus (OKN) is a visuomotor reflex permitting, with the vestibuloocular reflex (VOR), the stability of the image on the retina, during the displacement of the animal. OKN is composed of slow phases in the direction of the visual pattern motion and of resetting fast phases. One of the characteristics of this reflex is the directional selectivity of horizontal monocular OKN. The head and eye OKN display a directional asymmetry in monocular viewing condition: the stimulation in temporo-nasal (T-N) direction being always more eflicient than the stimulation in naso-temporal (N-T) direction. This characteristic of monocular OKN has been described in lower vertebrates. The directional asymmetry of monocular OKN might be related to the absence of a fovea (Tauber & Atkin, 1968), to the total decussation of the optic nerve (Fukuda, 1959) to the lateral position of the eyes (Gioanni, Rey, Villalobos & Dalbera, 1984)or to the level of cortical develop ment. But, none of these hypotheses suits to explain completely the presence or absence of The
*To whom correspondence should be addressed.
GABA
Directional selectivity
the directional symmetry through the OKN of all vertebrates. We have previously shown that in monocular viewing condition, an intravitreal injection of GABA antagonists into the open eye of the frog entailed the disappearance of the head OKN, this effect being related to the strong increase of the ganglion cell receptive field (Bonaventure, Wioland & Roussel, 1980). On the contrary, the injection of GABA antag onists into the closed eye or intraperitoneally provoked the appearance of a N-T component of the head OKN triggered by the non injected eye, so that the abolition of the directional asymmetry of monocular head OKN was observed (Bonaventure, Wioland & Bigenwald, 1983). This effect cannot be related to the modification of the retinal ganglion cell spatial organization, but could be explained by the action of the GABA antagonists on the central structures responsible for OKN, such as the pretectum and the nucleus of the basal optic root (Montgomery, Fite, Taylor & Bengston, 1982; Laxar, Alkonyi & Toth, 1983). In our previous work, the head OKN was evaluated by visual inspection and the parameter measured was the OKN extinction frequency i.e. the highest visual image frequency which still provoked a head OKN.
549
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H. YOKELet al.
The aim of the present paper is the following: to measure by the use of scleral search technique, both head and eye movements in the frog, after administration of GABAergic antagonist into the closed eye. With this technique, we want to test whether the GABAergic mechanisms responsible for directional asymmetry in the head OKN are also responsible for directional asymmetry in the eye OKN. MATERIALS
AND METHODS
In adult frogs (Runa esculenfu), monocular horizontal head and eye OKN was recorded by means of the scleral search coil technique before and after injection of picrotoxin into the closed eye. Stimulation To evoke horizontal head and eye OKN, the conditions of stimulation were identical. The animals were placed in the drum (300 mm in diameter and 450 mm in height) with alternative black and white vertical stripes, distributed equally on its inner surface (10 mm wide). The frogs were stimulated by an optokinetic drum rotating at constant speeds. The drum could be rotated clockwise and counterclockwise at constant speeds varying between 0.4 dag/sec and 50 deg/sec, by means of an electronic control system. The range of the constant drum spcais was between 1 and 25 dcg/sec for head and eye CXN. Room illumination was kept constant at 80 lux measured at the level of the frog’s eye. Eye and head OKN recording In order to record eye OKN, a magnetic coil system as described by Koch (1977) was used. One pair of coils (200 mm of diameter) carrying a current of 5OkHz frequency, generates a homogenous magnetic field. These coils were mounted on an immobile platform. The sensing coil, fixed on the eyeball and oriented ptrpendicularly to the interaural axis, was placed in the center of the magnetic 8cld. The vdtap in the sensing coil, proportional to the horiuwtal angular displacement, was amp&d, ractifjsd, filtered and recorded on a paper recorder (BBC). These analogical data were dig&&z& through an analog digital converter and put in a PC/AT computer; they were used to cakuiate the gain of the slow phase. Frogs were prepared under MS222 (&n&z) anaesthesia: a nut was 8xed to the skull by means of dental cement, and three metal screws
(1 mm in diameter) were implanted in the dorsal skull. In order to observe and to record monocular OKN, the lids of one eye were sutured, while the sclera of the other was exposed by removing the superior eyelid. After overnight recovery from anaesthesia, the frog’s head was restrained by attaching the nut fixed on the skull to the bar of the apparatus. The fixed head position was 15” nose up (Dieringer & Precht, 1982). The small sensing coil (1 mg, 75 turns, Sokymat) was perpendicularly secured under local anaesthesia on the sclera with a drop of glue just before the experiment. The electrical connection between this coil and the detection equipment was made by a pair of flexible isolated wires. The animal was placed in the optokinetic drum on an immobile platform. To record head OKN, the frog’s hind legs were restrained by a plaster on the immobile platform, and the sensing coil fixed to the skull under anaesthesia the day before experiment; the frog was placed at the center of the magnetic field. Before each recording, the system was calibrated: the linear relationship between the angular displacement of the sensing coil (in the center of the magnetic field), and the voltage was measured. Then the voltage induced in the sensing coil by an angular displacement of lo was calculated. The speed of the slow phase was measured from head or eye movement tracings, after the elimination of resetting fast phases and of very rapid head movements in the same direction of the stimulation. The slow phase speed and the slow phase velocity gain (the ratio of the slow phase speed to the drum speed) were calculated by software developed in the laboratory and running on an Unixsys PC/AT computer interfaced with the recording apparatus and with the drum tachymeter via the timer output and digital input of a RTI 800 (Analog Devices) interface. The frequency of resetting fast phases corresponds to the number of eye or head resetting fast phases during 20 sec. Picrotoxin, a non competitive GABA antagonist (provided by Sigma), was diluted in phosphate buffered saline (PBS) (pH = 7.3) and prepared daily. The picrotoxin concentration used was 5 mM, which is the concentration for which previously maximal effect on head monocular OKN was observed (Bonaventure et al., 1983). Thirty microliters of the solution were injected intravitreally by means of a microsyringe in the closed eye, under local anaesthesia (Cebesine, Chauvin Blache). Head and eye
Horizontal mwoeular head and eye OKN,
OKN recordings were made before administration of the drug, as well .ai’ 1 hr and 5 hr afterwards. To test the reversibility of the drug effect, some recordings were made 24 hr after picrotoxin administration. For statistical treatment, the standard deviation was noted in parentheses after the median value. We used the Wilcoxon signed ranks test and we indicated the level of significance (w) (Conover, 1971). RKSULTS (I) Control Monocular
OKN
(I) Before injection
Before injection, in monocular viewing condition, no spontaneous eye or head movement was recorded. The frog’s head and eye followed predominantly the stripes moving in the T-N direction. Stimulation in the N-T direction was significantly less efficient (Figs 1A and 3A). Monocular head OKN (Figs IA and 2). For T-N stimulation, frogs displayed a head OKN with slow phases following stripe motion and head resetting fast phases recentering head position. The average velocity gain measured with a drum speed of 3 deg/sec was 0.417 ( fO.176); it A
B
10s
Fig. I. Coil moordings of monocu&r head OKN evoked by constant drum spaeds in a monocular viewing condition. (A) Head recordings at d&rent drum speeds &fire drug injeetion; (B) one hour qfier intravitreal injection of pierotoxin (5 mh4) into the ekmed eye. The dir&ion of the stimulus (T-N for mmporo-nasal and N-T for naso-temporal) is indicPtodonthcMtof~rscordias.Thedrum~aorr indiated on the left of the tlgure. Arrows point to onset and to stop of the drum rotation. Calibration: the vertical bars cormspond to an angular displacement of 5” and the horizontal bar indieata a duration of lOsee.
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5 Speed
10
15
20
25
(dcg/s)
Fig. 2. Mean values of velocity gain of monocufur head OKh’ before (eireles) and 1hr (triangles) ufter picroloxin injection into the closed eye (n = 10). The velocity gain of monocular head OKN is plotted on the ordinate and the drum speed (in &g/see) on the abscissa. The OKN gain in response to T-N stimulus is drawn on the right and the OKN gain in response to N-T stimulus on the left of the graph. One hour after injection of pierotoxin into the closed eye, the velocity gain inermsed for all drum speeds used and for both directions of the stimulation. The vertical bars indicate the standard deviation.
progressively decreased with stimulus velocity, reaching 0.048 (kO.072) when the drum speed was 16deg/sec (n = 10) (Fig. 2). The average frequency of resetting fast phases was 1.5 ( f 1.2) when the drum was rotating at 3 deg/sec. For N-T stimulation, the frog’s head followed the stripes very slowly and several frogs did not move: the average velocity gain was 0.066 (&0.048) for a drum speed of 3 deg/sec. No resetting fast phase was observed when the stimulation was in the N-T direction. Monocular eye OKN. In this study, eye movements were recorded when the frog’s head was restrained. For T-N stimulation, frogs displayed an eye OKN with slow phases following stripe motion and eye resetting fast phases. The average velocity gain measured with a drum speed at 3 deg/sec, was 0.346 ( f 0.106); it progressively decreased with stimulus velocity, reaching 0.065 (&-0.047) when the drum speed was 15 deg/sec (n = 7). On the other hand, the average frequency of eye resetting fast phases which was 2.66 (f 1.5) (n = 7) when the drum was rotating at 1 deg/sec, increased to 6.428 (k4.07) when the drum speed was 9 deg/sec; for a higher drum speed (12 deg/sec), the average frequency of eye resetting fast phases was 2.54 ( f 2.28), (n = 5). For N-T stimulation, the frog’s eye followed the stripes very slowly: the average velocity gain was 0.031 (kO.021) for a drum speed of 3 deg/sec. It decreased with stimulus velocity. No eye resetting fast phase was observed when the stimulation was in the N-T direction.
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Y. H. Y~EL
et
al.
I
T-N
I
T-N
!
_L
We9 1
TN
T
1’
__A/ ,!
3drWr
15
10
5
Speed
(deg/s)
Fig. 4. Mean values of velocity gain of monocular zye OKN &jiwe (circks), and I hr aficr (trim&s) picrotoxin injection
TN
6degh
w
’ c
10s
.
Fig. 3. coil rccordjngs of moWci&W eye OKN evokad by constant drum spuds in a mcxo&ar viewing condition. (A) Eye reuxdings at dit&cnt dnun spa& W%re drug injection; (B) Ihr ufier intravitreal injaction of pkrotoxin (5 mM) into the c&xl eye. The direction of the stimulus (T-N for tcmporo-nasal and N-T fur nac+tamporal) is indicot#lonthcleftoftoch~~Thdwnspc#lrarr indicPtcdonthefefloftbe~~.~~poiDttaoarctand to stop of the drum rotation. calibration: the varkal bars wrraspand to an angular mt of 5” and the horizaatal bar indicates a duration of lOsac.
The diiferencc between the velocity gain of OKN (eye or kad) evoked by a T-N stimulation and that evoked by a N-T atimulation, is signi&cant for all drum es ueed, the eye or head predominantly f&lowing the pattern motion in the T-N direction (W < 0.01). (2) The injection of the v&de
(PBS)
This had no e&et on head (n - 3) and eye OKN (n - 3) parameters. (II) E$ects on A4onoudar Heud OKN ofan Intrav&eal hi$ection of Picmtoxin (5mM) into the Closed Eye (F&p IB and 2) After drug injection, no spontaneous head movement was oheerved. For T-N stimulation, and less than half an hour after injection, frog’s he& began to foilow stripe motion very quickly. One hour after picrotoxin injection, the 8ver8ge v&i&y g&n increased signi&antly for all drum SpaQds used (w c OJIOS): for example the v&city gain measured with a drum speed st 3ck&hcc increased from 0.417 (iO.176) to 0.724 (fO.144) (?I = 10). The average frequency of had resetting fast phases incmnsed tly: it increased from 2.03 ( f f .6) to 3.26 ( f I .83) for drum speed of 3 deg/sec (W < 0.005).
into the closed eye (N = 7). The velocity gain of monocular eye OKN is plotted on the ordinate and the drum (in de&cc) on the abscissa. The OKN gain in response to T-N stimulus is drawn on the right and the OKN gain in response to N-T stimulus on the left of each wph. One hour after inja%ion of picrcxoxin into the closed eye, the vcitity @n id only for the eye OKN evoked by a N-T atimulation. while it was not mod&d by a T-N stimulation. This incrca~ was signifkant, for all drum speeds used. The vertical bare indicate the standard deviation.
For N-T stimulation, frogs d&played a head OKN with slow phases following stripe motion and kad resetting fast phases contrary to what was observed before injection. The aver8ge velocity gain increased significantly for ati drum speeds tested (W c 0.005): for exanq$e, the average velocity gain for a drum speed of 3 d@ec, which was 0.066 (~0.048) before injection, increased to 0.6@ ( f 0.547) i hr after (?I = 10). In addition, picrotoxin injection provoked an increase of both T-N and N-T components of the head OKN. In several frogs, it was observed that the OKN slow phases were interrupted, not only by the resetting fast phases, but also by very rapid head movements of Iarge amplitude in the direction of the stimulus, as seen in the three upper recordings of Fig. 11). These movements were recorded for both directions of stimulation and they stopped when stopping the drum rotation. All these effects were reversible, less than 24 hr after injection. (HZ) Eflects on A4onocukr Eye Oi#3 of an I@ctim of Picrotaxkr (51aM) &to the Closed Eye
hmwitred
No spontaaeous eye movement or eye shift were &served after picrotoxin injnetion. For T-N stimulation, eye OKN veMty .gain and eye resetting fast phase frequency rem&ted unchanged and similar to those observ&b&re injection, for all drum speeds (w > 0.05).
Horizontal monocular head and eye OKN Table I. Mean values and standard deviations of the frequency of the eye r.f.p. of monoculqqc OKN for@@ T-N and N-T directions of stimulatidn at different drum speeds before and 1 hr after picrotoxin administration Drum speed (de&W I 3 6 9 12
Before picrotoxin
After picrotoxin
T-N
N-T
T-N
N-T
n
2.6& 1.5 3.7*1.4 5.3 k2.7 6.4k4.1 6.Ok2.6
0 0 0 0 0
2.8 f 1.3 5.5i2.3 5.9*3.5 4.6k2.3 4.7ki.5
1.1*1.2 2.7k1.4 2.0*1.1 2.4& 1.8 2.6f2.4
7 7 7 7 5
For N-T stimulation, frogs displayed an eye OKN with slow phases following stripe motion, and eye resetting fast phases, contrary to that observed before injection. One hour after drug administration, the average velocity gain increased significantly for all drum speeds used (W < 0.01). For example, for a drum speed of 3 deg/sec, it increased from 0.031 (kO.021) before injection to 0.297 (fO.l35), 1 hr after injection. The frequency of eye resetting fast phases was also significantly increased (w < 0.01) (Table 1): for a drum speed of 3 deg/sec the frequency of eye resetting fast phases which was nil1 before injection increased to 2.71 (i- 1.38) after. As it was observed in the head OKN, 1 hr after picrotoxin injection, the difference between the velocity gain of eye OKN evoked by a T-N stimulation and that evoked by a N-T stimulation was not significant (w > O.OS), with drum speeds at 3 deg/sec, 6 deg/sec and 9 deg/sec. For the lowest (1 deg/sec) and the highest (12 deg/sec) drum speeds, the difference remained significant (w < 0.05). However, it decreased significantly compared to that measured before injection. The difference between the frequency of eye resetting fast phases, OKN evoked by a T-N stimulation and that evoked by a N-T stimulation remained significant 1 hr after drug injection (w < O.OS),but it was significantly decreased compared to that observed before injection, for all drum speeds used (w < 0.01). DiSCUSSION
In monocular vision, the frog displays an asymmetrical eye and head OKN in favour of the T-N component, as was already observed by Birukow (1937), Dieringer and Precht (1982) and Yticel, Jardon and Bonaventure (1989). The slow phase velocity gain and the frequency of resetting fast phases of eye or head OKN evoked by a T-N stimulation were significantly
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higher than those observed when the stimulation Was in the N-T direction. The intravitreal injection of picrotoxin (GABA antagonist) into the closed eye, provoked the appearance of a N-T component in the monocular head OKN: the increase of both the velocity gain and the head resetting fast phases, for a stimulation in the N-T direction was strong and significant. The directional asymmetry between the T-N and the N-T components of monocular head OKN was reduced, even abolished. In addition, in the head OKN, the injection of picrotoxin provoked a strong facilitation for both T-N and N-T directions of stimulation: slow phase gain of both components was increased. The frequency of resetting fast phases was also markedly enhanced but the presence of rapid movements of large amplitude during the optokinetic stimulation, should make us cautious in the interpretation of this result. Thus, the administration of picrotoxin not only abolished the directional asymmetry, but provoked also an increase in the performances of the both (T-N and N-T) components of monocular head OKN. These data are in agreement with our previous observations based on the quanti&ation of the nystagmus extinction speed: namely the highest frequency of stimulation which still provokes a head OKN (Bonaventure et al., 1983). In these previous experiments, it was already shown that GABAergic mechanisms are involved in the directional asymmetry of the monocular head OKN. This result was well confirmed by the measure of the velocity gain and the resetting fast phase frequency of monocular head OKN but also of the monocular eye OKN. The injection of picrotoxin into the closed eye provoked the appearance of the N-T component of the monocular eye OKN also, with a strong increase of both the velocity gain and the frequency of eye resetting fast phases when the stimulation was in the N-T direction. After picrotoxin administration, the difference between the velocity gain of monocular OKN evoked by a T-N stimulation and that evoked by a N-T stimulation decreased significantly for all drum speeds used. Contrary to what was observed in head OKN, the T-N component of monocular eye OKN was not modified. These results suggest that GABAergic mechanisms, blocked by picrotoxin, are also involved in the directional asymmetry of the monocular eye OKN. The additional inhibition upon both components of head OKN, was not observed in eye OKN.
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OKN triggered by the contralateral eye (paper From the total of our results, we could deduce in preparation). It is then tempting to suggest that there are two distinct GABAergic inthat the directional selectivity displayed by hibitory systems: the first one common for head the frog pretectal cells mainly for the T-N and eye OKN, blocking the N-T component; direction (Kondrashev & Orlov, 1976; Katte & the second acting on both T-N and N-T comHoffmann, 1980; Cochran, Dieringer & Precht, ponents of the monocular head OKN only. It is interesting to remember that the injection of 1984) could be determined by GABAergic competitive GABA antagonists (bicuculline and mechanism, as it was demonstrated for other SR 95103) into the closed eye, provoked only direction selective neurons: the rabbit retinal ganglion cells and the cat visual cortex cells the appearance of the N-T component, and not the increase of both components of the (Caldwell, Daw & Wyatt, 1978; Sillito, 1977). The appearance of a N-T component after monocular head OKN (Bonaventure, Wioland GABA antagonist administration might then be & Jardon, 1985). This fact suggest that the N-T provoked by the modification of the directional component inhibition is blocked by competitive selectivity of the pretectal cells, by the blockade as well as non competitive GABA antagonists, while the second inhibition, is only sensitive to of the GABAergic system. Moreover, parallel increase of both T-N and picrotoxin. Our data reinforce the hypothesis on the N-T components in the monocular head OKN involvement of GABAergic mechanisms in the as well as the appearance of additional rapid head movements of large amplitude, observed directional asymmetry of the monocular head and eye OKN. However, they do not allow us after picrotoxin administration suggest that this further inhibition insensitive to bicuculline acts to localize the site of action of these inhibitory systems. We have previously shown that the on structures which are involved in the origin injected drugs intervened at a retinal level as of the head movements only. This additional inhibition might modulate either directly or well as at a central level (Bonaventure, Jardon, Wioland, Yiiccl & Rudolf, 1988). When injected indirectly the motor output involved in the head into the open eye, the GABA antagonists promovements. voked modifications in the spatial organization Acknowfedgcmenrs-The authors wish to thank E. Dreyfus of the retinal input which could be responsible for electronic help, U. Salci for the software and G. Rudolf for the abolition of the OKN triggered by the for iconography. injected eye (Bonaventure et al., 1980, 1983). This study was supported by a grant of the Foundation On the contrary, the appearance of the N-T pour la Recherche MCdicale Fran&se. component in the monocular eye and head OKN, after intraperitoneal administration or intravitreal injection of picrotoxin into the REFERENcFS closed eye, suggests that GABA must intervene in central structures, which have not yet been Birukow, G. (1937). Untemuchungen iiber den optis&n Drehnystagmus uber die !Msch&fe des GrMw&es determined. However, mesenaphalic visual (Rana tmporaria). Zeirschrijif? Vergkikhendep&j&relay nuclei like the pretectal nuclei and the gie. 2.5, 92-142. nucleus of the basal optic root (nBOR) are Bonaventure, N.. Wioland, N. & Roussel, G. (1980). Effects of some amino acids (GABA. glycine, taurine) and thejr involved in both head and eye OKN antagonists (picrotoxin, strychnkre) on spatial and tern-(Montgomery et al., 1982; Lazar et al., 1983). polrl features of frog rctia8l gangiion cell m. We suggest that GABA antagonists which I@&ers A&iv, 385, 51-64. provoke the appearance of the N-T component Bonaventure, N., Wioland, N. & Bigenwaid, J. (1983). and abolish the directional asymmetry of the Involvement of GABA-ergic mechanisms in the optokinetic nystagmus of the frog. ExperimenrolBrain Re~w&, monocular eye and head OKN, could block the 50,433-441. GABAergic inhibition at this level. Our results Boaavcnture,N., Wioiand, N. 8r Jardon, B. (1985). On showing the very high density of glutamic GABA-eqtic me&an&s in the opt#netic m of acid decarboxylase (the GABA synthetizing the frog: Bfreotsof bicundliae, auyit#*na and SR 95103. enzyme) immunoreactive axon terminals in the a new GARA antapniat.Etuapean JWMI of Mamadogy, 118, 61-68. pretectal nuclei (Y&XI, Hindeiang, Stoeckel 8t Bcmamturc, N., Jardon, B., Wioland, N., Yiiuel, H. & Bonaventure, 1988), support this hypothesis. Rudolf. 0. (1988). On &oline& me&a* in the On the other hand, microinjections of GABA optokinctk nystagmus of the free: Ansgktr of antagonists into the pretcctum, provoked the muscar& and nicotinic systems. &&x&s& w appearance of a N-T component in the eye Research, 27. 59-7 1.
Horizontal monocular head and eye OKN Caldwell, J. H., Daw, N. W. & Wyatt, H. J. (1978). Etfects of picrotoxin and strychnine on rabbit retinal ganglion cellsz Lateral interactions for cells with more complex recep tive fields. Journal of Physiology (London), 276277-298. Cochran, S. L., Dieringer, N. & Precht, W. (1984). Basic optokinetic ocular reflex pathways in the frog. Joumul of Neuroscience, 4, 43-57. Conover, W. J. (1971). The use of ranks. In Prucriccrlnon pammerric statistics (pp. 203-216). New York: Wiley. Dieringer, N. & Precht, W. (1982). Compensatory head and eye movement in the frog and their contribution to stabilization of gaze. Experimental Brain Research, 47, 394-406. Fukuda, T. (1959). The unidirectionality of the labyrinthinc reflex in relation to the unidirectionality of the optokinetic reflex. Acfo Ofo-Luryngologica, 50, 507-516. Gioanni, H., Rey, J., Villalobos. J. & Dalbera, A. (1984). Single unit activity in the nucleus of the basal optic root (nBOR) during optokinetic, vestibular and visuo-vestibular stimulations in the alert pigeon (Columbia Iiuiu). Experimenral Brain Research, 57, 49-60. Katte, 0. & Hoffinann, K.-P. (1980). Direction specific neurons in the pretectum of the frog (Runu esnrlcnru). Journal of Comparative Physiology, 140, 53-57. Koch, U. T. (1977). A miniature movement detector applied to recording beats in the locusta. Fortschritte &r Zoologie. 24, 327-332.
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Kondrashev. S. L. & Orlov. 0. Y. (1976). Directionsensitive neurons in the frog visual system. Neirojziologie, 8. 196198. Laxar, G.. Alkonyi. B. & Toth, P. (1983). J&-investigation of the role of the accessory optic system and pretectum in the horizontal optokinetic head nystagmus of the frog. Lesion experiments. Acta Biologica Hungarica, 34, 385-393. Montgomery, N.. Fite, K. V., Taylor, M. & Bengston, L. (1982). Neuron correlates of optokinetic nystagmus in the mesencephalon of Rwta pipiens: Functional analysis. Brain Behaviour and Evohuion, 21, 137-153. Sillito, A. M. (1977). Inhibitory processes underlying the directional specificity of simple, complex and hypercomplex cells in the cat’s visual cortex. Journal of Physiology (London), 271. 699-721. Tauber, E. S. & Atkin. A. (1968). Optomotor responses to monocular stimulation: Relation to visual system organixation. Science MO, 1365-1367. YticeJ, Y. H., Hi&huq, C., Stoe&J, hf. E. & Bonavemure, N. (1988). GAD immunoreactivity in pretectal and accessory optic nuclei of the frog mesencephalon. Neuroscience Letters, 84, l-6. Yiicel, Y. H., Jardon, B. and Bonaventure, N. (1989). Involvement of ON and OFF retinal channels in the eye and head horizontal optokinetic nystagmus of the frog. Visual Neuroscience, 5 357-365.
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DIRECTIONAL ASYMMETRY OF THE HORIZONTAL MONOCULAR HEAD AND EYE OPTOKINETIC NYSTAGMUS: EFFECTS OF PICROTOXIN Y. H. Y&EL, B. JARDON,M.-S. KIM and N. BONAVENTIJRE* Dtpartement de Neurophysiologie et Biologic des Comportements, Centre de Neurochimic du CNRS, Strasbourg, France (Received 21 June 1989; in revised form 14 Augusr 1989) Abstract-Frog monocular aye and head optokinetic nystagmus (OKN) wara studiad by coil recordings aftex 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. Optokinetic nystagmus Frog
Eye movement
Head movement
iNTltODUC3ION
optokinetic nystagmus (OKN) is a visuomotor reflex permitting, with the vestibuloocular reflex (VOR), the stability of the image on the retina, during the displacement of the animal. OKN is composed of slow phases in the direction of the visual pattern motion and of resetting fast phases. One of the characteristics of this reflex is the directional selectivity of horizontal monocular OKN. The head and eye OKN display a directional asymmetry in monocular viewing condition: the stimulation in temporo-nasal (T-N) direction being always more eflicient than the stimulation in naso-temporal (N-T) direction. This characteristic of monocular OKN has been described in lower vertebrates. The directional asymmetry of monocular OKN might be related to the absence of a fovea (Tauber & Atkin, 1968), to the total decussation of the optic nerve (Fukuda, 1959) to the lateral position of the eyes (Gioanni, Rey, Villalobos & Dalbera, 1984)or to the level of cortical develop ment. But, none of these hypotheses suits to explain completely the presence or absence of The
*To whom correspondence should be addressed.
GABA
Directional selectivity
the directional symmetry through the OKN of all vertebrates. We have previously shown that in monocular viewing condition, an intravitreal injection of GABA antagonists into the open eye of the frog entailed the disappearance of the head OKN, this effect being related to the strong increase of the ganglion cell receptive field (Bonaventure, Wioland & Roussel, 1980). On the contrary, the injection of GABA antag onists into the closed eye or intraperitoneally provoked the appearance of a N-T component of the head OKN triggered by the non injected eye, so that the abolition of the directional asymmetry of monocular head OKN was observed (Bonaventure, Wioland & Bigenwald, 1983). This effect cannot be related to the modification of the retinal ganglion cell spatial organization, but could be explained by the action of the GABA antagonists on the central structures responsible for OKN, such as the pretectum and the nucleus of the basal optic root (Montgomery, Fite, Taylor & Bengston, 1982; Laxar, Alkonyi & Toth, 1983). In our previous work, the head OKN was evaluated by visual inspection and the parameter measured was the OKN extinction frequency i.e. the highest visual image frequency which still provoked a head OKN.
549
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Y.
H. YOKELet al.
The aim of the present paper is the following: to measure by the use of scleral search technique, both head and eye movements in the frog, after administration of GABAergic antagonist into the closed eye. With this technique, we want to test whether the GABAergic mechanisms responsible for directional asymmetry in the head OKN are also responsible for directional asymmetry in the eye OKN. MATERIALS
AND METHODS
In adult frogs (Runa esculenfu), monocular horizontal head and eye OKN was recorded by means of the scleral search coil technique before and after injection of picrotoxin into the closed eye. Stimulation To evoke horizontal head and eye OKN, the conditions of stimulation were identical. The animals were placed in the drum (300 mm in diameter and 450 mm in height) with alternative black and white vertical stripes, distributed equally on its inner surface (10 mm wide). The frogs were stimulated by an optokinetic drum rotating at constant speeds. The drum could be rotated clockwise and counterclockwise at constant speeds varying between 0.4 dag/sec and 50 deg/sec, by means of an electronic control system. The range of the constant drum spcais was between 1 and 25 dcg/sec for head and eye CXN. Room illumination was kept constant at 80 lux measured at the level of the frog’s eye. Eye and head OKN recording In order to record eye OKN, a magnetic coil system as described by Koch (1977) was used. One pair of coils (200 mm of diameter) carrying a current of 5OkHz frequency, generates a homogenous magnetic field. These coils were mounted on an immobile platform. The sensing coil, fixed on the eyeball and oriented ptrpendicularly to the interaural axis, was placed in the center of the magnetic 8cld. The vdtap in the sensing coil, proportional to the horiuwtal angular displacement, was amp&d, ractifjsd, filtered and recorded on a paper recorder (BBC). These analogical data were dig&&z& through an analog digital converter and put in a PC/AT computer; they were used to cakuiate the gain of the slow phase. Frogs were prepared under MS222 (&n&z) anaesthesia: a nut was 8xed to the skull by means of dental cement, and three metal screws
(1 mm in diameter) were implanted in the dorsal skull. In order to observe and to record monocular OKN, the lids of one eye were sutured, while the sclera of the other was exposed by removing the superior eyelid. After overnight recovery from anaesthesia, the frog’s head was restrained by attaching the nut fixed on the skull to the bar of the apparatus. The fixed head position was 15” nose up (Dieringer & Precht, 1982). The small sensing coil (1 mg, 75 turns, Sokymat) was perpendicularly secured under local anaesthesia on the sclera with a drop of glue just before the experiment. The electrical connection between this coil and the detection equipment was made by a pair of flexible isolated wires. The animal was placed in the optokinetic drum on an immobile platform. To record head OKN, the frog’s hind legs were restrained by a plaster on the immobile platform, and the sensing coil fixed to the skull under anaesthesia the day before experiment; the frog was placed at the center of the magnetic field. Before each recording, the system was calibrated: the linear relationship between the angular displacement of the sensing coil (in the center of the magnetic field), and the voltage was measured. Then the voltage induced in the sensing coil by an angular displacement of lo was calculated. The speed of the slow phase was measured from head or eye movement tracings, after the elimination of resetting fast phases and of very rapid head movements in the same direction of the stimulation. The slow phase speed and the slow phase velocity gain (the ratio of the slow phase speed to the drum speed) were calculated by software developed in the laboratory and running on an Unixsys PC/AT computer interfaced with the recording apparatus and with the drum tachymeter via the timer output and digital input of a RTI 800 (Analog Devices) interface. The frequency of resetting fast phases corresponds to the number of eye or head resetting fast phases during 20 sec. Picrotoxin, a non competitive GABA antagonist (provided by Sigma), was diluted in phosphate buffered saline (PBS) (pH = 7.3) and prepared daily. The picrotoxin concentration used was 5 mM, which is the concentration for which previously maximal effect on head monocular OKN was observed (Bonaventure et al., 1983). Thirty microliters of the solution were injected intravitreally by means of a microsyringe in the closed eye, under local anaesthesia (Cebesine, Chauvin Blache). Head and eye
Horizontal mwoeular head and eye OKN,
OKN recordings were made before administration of the drug, as well .ai’ 1 hr and 5 hr afterwards. To test the reversibility of the drug effect, some recordings were made 24 hr after picrotoxin administration. For statistical treatment, the standard deviation was noted in parentheses after the median value. We used the Wilcoxon signed ranks test and we indicated the level of significance (w) (Conover, 1971). RKSULTS (I) Control Monocular
OKN
(I) Before injection
Before injection, in monocular viewing condition, no spontaneous eye or head movement was recorded. The frog’s head and eye followed predominantly the stripes moving in the T-N direction. Stimulation in the N-T direction was significantly less efficient (Figs 1A and 3A). Monocular head OKN (Figs IA and 2). For T-N stimulation, frogs displayed a head OKN with slow phases following stripe motion and head resetting fast phases recentering head position. The average velocity gain measured with a drum speed of 3 deg/sec was 0.417 ( fO.176); it A
B
10s
Fig. I. Coil moordings of monocu&r head OKN evoked by constant drum spaeds in a monocular viewing condition. (A) Head recordings at d&rent drum speeds &fire drug injeetion; (B) one hour qfier intravitreal injection of pierotoxin (5 mh4) into the ekmed eye. The dir&ion of the stimulus (T-N for mmporo-nasal and N-T for naso-temporal) is indicPtodonthcMtof~rscordias.Thedrum~aorr indiated on the left of the tlgure. Arrows point to onset and to stop of the drum rotation. Calibration: the vertical bars cormspond to an angular displacement of 5” and the horizontal bar indieata a duration of lOsee.
551
5 Speed
10
15
20
25
(dcg/s)
Fig. 2. Mean values of velocity gain of monocufur head OKh’ before (eireles) and 1hr (triangles) ufter picroloxin injection into the closed eye (n = 10). The velocity gain of monocular head OKN is plotted on the ordinate and the drum speed (in &g/see) on the abscissa. The OKN gain in response to T-N stimulus is drawn on the right and the OKN gain in response to N-T stimulus on the left of the graph. One hour after injection of pierotoxin into the closed eye, the velocity gain inermsed for all drum speeds used and for both directions of the stimulation. The vertical bars indicate the standard deviation.
progressively decreased with stimulus velocity, reaching 0.048 (kO.072) when the drum speed was 16deg/sec (n = 10) (Fig. 2). The average frequency of resetting fast phases was 1.5 ( f 1.2) when the drum was rotating at 3 deg/sec. For N-T stimulation, the frog’s head followed the stripes very slowly and several frogs did not move: the average velocity gain was 0.066 (&0.048) for a drum speed of 3 deg/sec. No resetting fast phase was observed when the stimulation was in the N-T direction. Monocular eye OKN. In this study, eye movements were recorded when the frog’s head was restrained. For T-N stimulation, frogs displayed an eye OKN with slow phases following stripe motion and eye resetting fast phases. The average velocity gain measured with a drum speed at 3 deg/sec, was 0.346 ( f 0.106); it progressively decreased with stimulus velocity, reaching 0.065 (&-0.047) when the drum speed was 15 deg/sec (n = 7). On the other hand, the average frequency of eye resetting fast phases which was 2.66 (f 1.5) (n = 7) when the drum was rotating at 1 deg/sec, increased to 6.428 (k4.07) when the drum speed was 9 deg/sec; for a higher drum speed (12 deg/sec), the average frequency of eye resetting fast phases was 2.54 ( f 2.28), (n = 5). For N-T stimulation, the frog’s eye followed the stripes very slowly: the average velocity gain was 0.031 (kO.021) for a drum speed of 3 deg/sec. It decreased with stimulus velocity. No eye resetting fast phase was observed when the stimulation was in the N-T direction.
552
Y. H. Y~EL
et
al.
I
T-N
I
T-N
!
_L
We9 1
TN
T
1’
__A/ ,!
3drWr
15
10
5
Speed
(deg/s)
Fig. 4. Mean values of velocity gain of monocular zye OKN &jiwe (circks), and I hr aficr (trim&s) picrotoxin injection
TN
6degh
w
’ c
10s
.
Fig. 3. coil rccordjngs of moWci&W eye OKN evokad by constant drum spuds in a mcxo&ar viewing condition. (A) Eye reuxdings at dit&cnt dnun spa& W%re drug injection; (B) Ihr ufier intravitreal injaction of pkrotoxin (5 mM) into the c&xl eye. The direction of the stimulus (T-N for tcmporo-nasal and N-T fur nac+tamporal) is indicot#lonthcleftoftoch~~Thdwnspc#lrarr indicPtcdonthefefloftbe~~.~~poiDttaoarctand to stop of the drum rotation. calibration: the varkal bars wrraspand to an angular mt of 5” and the horizaatal bar indicates a duration of lOsac.
The diiferencc between the velocity gain of OKN (eye or kad) evoked by a T-N stimulation and that evoked by a N-T atimulation, is signi&cant for all drum es ueed, the eye or head predominantly f&lowing the pattern motion in the T-N direction (W < 0.01). (2) The injection of the v&de
(PBS)
This had no e&et on head (n - 3) and eye OKN (n - 3) parameters. (II) E$ects on A4onoudar Heud OKN ofan Intrav&eal hi$ection of Picmtoxin (5mM) into the Closed Eye (F&p IB and 2) After drug injection, no spontaneous head movement was oheerved. For T-N stimulation, and less than half an hour after injection, frog’s he& began to foilow stripe motion very quickly. One hour after picrotoxin injection, the 8ver8ge v&i&y g&n increased signi&antly for all drum SpaQds used (w c OJIOS): for example the v&city gain measured with a drum speed st 3ck&hcc increased from 0.417 (iO.176) to 0.724 (fO.144) (?I = 10). The average frequency of had resetting fast phases incmnsed tly: it increased from 2.03 ( f f .6) to 3.26 ( f I .83) for drum speed of 3 deg/sec (W < 0.005).
into the closed eye (N = 7). The velocity gain of monocular eye OKN is plotted on the ordinate and the drum (in de&cc) on the abscissa. The OKN gain in response to T-N stimulus is drawn on the right and the OKN gain in response to N-T stimulus on the left of each wph. One hour after inja%ion of picrcxoxin into the closed eye, the vcitity @n id only for the eye OKN evoked by a N-T atimulation. while it was not mod&d by a T-N stimulation. This incrca~ was signifkant, for all drum speeds used. The vertical bare indicate the standard deviation.
For N-T stimulation, frogs d&played a head OKN with slow phases following stripe motion and kad resetting fast phases contrary to what was observed before injection. The aver8ge velocity gain increased significantly for ati drum speeds tested (W c 0.005): for exanq$e, the average velocity gain for a drum speed of 3 d@ec, which was 0.066 (~0.048) before injection, increased to 0.6@ ( f 0.547) i hr after (?I = 10). In addition, picrotoxin injection provoked an increase of both T-N and N-T components of the head OKN. In several frogs, it was observed that the OKN slow phases were interrupted, not only by the resetting fast phases, but also by very rapid head movements of Iarge amplitude in the direction of the stimulus, as seen in the three upper recordings of Fig. 11). These movements were recorded for both directions of stimulation and they stopped when stopping the drum rotation. All these effects were reversible, less than 24 hr after injection. (HZ) Eflects on A4onocukr Eye Oi#3 of an I@ctim of Picrotaxkr (51aM) &to the Closed Eye
hmwitred
No spontaaeous eye movement or eye shift were &served after picrotoxin injnetion. For T-N stimulation, eye OKN veMty .gain and eye resetting fast phase frequency rem&ted unchanged and similar to those observ&b&re injection, for all drum speeds (w > 0.05).
Horizontal monocular head and eye OKN Table I. Mean values and standard deviations of the frequency of the eye r.f.p. of monoculqqc OKN for@@ T-N and N-T directions of stimulatidn at different drum speeds before and 1 hr after picrotoxin administration Drum speed (de&W I 3 6 9 12
Before picrotoxin
After picrotoxin
T-N
N-T
T-N
N-T
n
2.6& 1.5 3.7*1.4 5.3 k2.7 6.4k4.1 6.Ok2.6
0 0 0 0 0
2.8 f 1.3 5.5i2.3 5.9*3.5 4.6k2.3 4.7ki.5
1.1*1.2 2.7k1.4 2.0*1.1 2.4& 1.8 2.6f2.4
7 7 7 7 5
For N-T stimulation, frogs displayed an eye OKN with slow phases following stripe motion, and eye resetting fast phases, contrary to that observed before injection. One hour after drug administration, the average velocity gain increased significantly for all drum speeds used (W < 0.01). For example, for a drum speed of 3 deg/sec, it increased from 0.031 (kO.021) before injection to 0.297 (fO.l35), 1 hr after injection. The frequency of eye resetting fast phases was also significantly increased (w < 0.01) (Table 1): for a drum speed of 3 deg/sec the frequency of eye resetting fast phases which was nil1 before injection increased to 2.71 (i- 1.38) after. As it was observed in the head OKN, 1 hr after picrotoxin injection, the difference between the velocity gain of eye OKN evoked by a T-N stimulation and that evoked by a N-T stimulation was not significant (w > O.OS), with drum speeds at 3 deg/sec, 6 deg/sec and 9 deg/sec. For the lowest (1 deg/sec) and the highest (12 deg/sec) drum speeds, the difference remained significant (w < 0.05). However, it decreased significantly compared to that measured before injection. The difference between the frequency of eye resetting fast phases, OKN evoked by a T-N stimulation and that evoked by a N-T stimulation remained significant 1 hr after drug injection (w < O.OS),but it was significantly decreased compared to that observed before injection, for all drum speeds used (w < 0.01). DiSCUSSION
In monocular vision, the frog displays an asymmetrical eye and head OKN in favour of the T-N component, as was already observed by Birukow (1937), Dieringer and Precht (1982) and Yticel, Jardon and Bonaventure (1989). The slow phase velocity gain and the frequency of resetting fast phases of eye or head OKN evoked by a T-N stimulation were significantly
553
higher than those observed when the stimulation Was in the N-T direction. The intravitreal injection of picrotoxin (GABA antagonist) into the closed eye, provoked the appearance of a N-T component in the monocular head OKN: the increase of both the velocity gain and the head resetting fast phases, for a stimulation in the N-T direction was strong and significant. The directional asymmetry between the T-N and the N-T components of monocular head OKN was reduced, even abolished. In addition, in the head OKN, the injection of picrotoxin provoked a strong facilitation for both T-N and N-T directions of stimulation: slow phase gain of both components was increased. The frequency of resetting fast phases was also markedly enhanced but the presence of rapid movements of large amplitude during the optokinetic stimulation, should make us cautious in the interpretation of this result. Thus, the administration of picrotoxin not only abolished the directional asymmetry, but provoked also an increase in the performances of the both (T-N and N-T) components of monocular head OKN. These data are in agreement with our previous observations based on the quanti&ation of the nystagmus extinction speed: namely the highest frequency of stimulation which still provokes a head OKN (Bonaventure et al., 1983). In these previous experiments, it was already shown that GABAergic mechanisms are involved in the directional asymmetry of the monocular head OKN. This result was well confirmed by the measure of the velocity gain and the resetting fast phase frequency of monocular head OKN but also of the monocular eye OKN. The injection of picrotoxin into the closed eye provoked the appearance of the N-T component of the monocular eye OKN also, with a strong increase of both the velocity gain and the frequency of eye resetting fast phases when the stimulation was in the N-T direction. After picrotoxin administration, the difference between the velocity gain of monocular OKN evoked by a T-N stimulation and that evoked by a N-T stimulation decreased significantly for all drum speeds used. Contrary to what was observed in head OKN, the T-N component of monocular eye OKN was not modified. These results suggest that GABAergic mechanisms, blocked by picrotoxin, are also involved in the directional asymmetry of the monocular eye OKN. The additional inhibition upon both components of head OKN, was not observed in eye OKN.
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Y. H. YUCEL et al.
OKN triggered by the contralateral eye (paper From the total of our results, we could deduce in preparation). It is then tempting to suggest that there are two distinct GABAergic inthat the directional selectivity displayed by hibitory systems: the first one common for head the frog pretectal cells mainly for the T-N and eye OKN, blocking the N-T component; direction (Kondrashev & Orlov, 1976; Katte & the second acting on both T-N and N-T comHoffmann, 1980; Cochran, Dieringer & Precht, ponents of the monocular head OKN only. It is interesting to remember that the injection of 1984) could be determined by GABAergic competitive GABA antagonists (bicuculline and mechanism, as it was demonstrated for other SR 95103) into the closed eye, provoked only direction selective neurons: the rabbit retinal ganglion cells and the cat visual cortex cells the appearance of the N-T component, and not the increase of both components of the (Caldwell, Daw & Wyatt, 1978; Sillito, 1977). The appearance of a N-T component after monocular head OKN (Bonaventure, Wioland GABA antagonist administration might then be & Jardon, 1985). This fact suggest that the N-T provoked by the modification of the directional component inhibition is blocked by competitive selectivity of the pretectal cells, by the blockade as well as non competitive GABA antagonists, while the second inhibition, is only sensitive to of the GABAergic system. Moreover, parallel increase of both T-N and picrotoxin. Our data reinforce the hypothesis on the N-T components in the monocular head OKN involvement of GABAergic mechanisms in the as well as the appearance of additional rapid head movements of large amplitude, observed directional asymmetry of the monocular head and eye OKN. However, they do not allow us after picrotoxin administration suggest that this further inhibition insensitive to bicuculline acts to localize the site of action of these inhibitory systems. We have previously shown that the on structures which are involved in the origin injected drugs intervened at a retinal level as of the head movements only. This additional inhibition might modulate either directly or well as at a central level (Bonaventure, Jardon, Wioland, Yiiccl & Rudolf, 1988). When injected indirectly the motor output involved in the head into the open eye, the GABA antagonists promovements. voked modifications in the spatial organization Acknowfedgcmenrs-The authors wish to thank E. Dreyfus of the retinal input which could be responsible for electronic help, U. Salci for the software and G. Rudolf for the abolition of the OKN triggered by the for iconography. injected eye (Bonaventure et al., 1980, 1983). This study was supported by a grant of the Foundation On the contrary, the appearance of the N-T pour la Recherche MCdicale Fran&se. component in the monocular eye and head OKN, after intraperitoneal administration or intravitreal injection of picrotoxin into the REFERENcFS closed eye, suggests that GABA must intervene in central structures, which have not yet been Birukow, G. (1937). Untemuchungen iiber den optis&n Drehnystagmus uber die !Msch&fe des GrMw&es determined. However, mesenaphalic visual (Rana tmporaria). Zeirschrijif? Vergkikhendep&j&relay nuclei like the pretectal nuclei and the gie. 2.5, 92-142. nucleus of the basal optic root (nBOR) are Bonaventure, N.. Wioland, N. & Roussel, G. (1980). Effects of some amino acids (GABA. glycine, taurine) and thejr involved in both head and eye OKN antagonists (picrotoxin, strychnkre) on spatial and tern-(Montgomery et al., 1982; Lazar et al., 1983). polrl features of frog rctia8l gangiion cell m. We suggest that GABA antagonists which I@&ers A&iv, 385, 51-64. provoke the appearance of the N-T component Bonaventure, N., Wioland, N. & Bigenwaid, J. (1983). and abolish the directional asymmetry of the Involvement of GABA-ergic mechanisms in the optokinetic nystagmus of the frog. ExperimenrolBrain Re~w&, monocular eye and head OKN, could block the 50,433-441. GABAergic inhibition at this level. Our results Boaavcnture,N., Wioiand, N. 8r Jardon, B. (1985). On showing the very high density of glutamic GABA-eqtic me&an&s in the opt#netic m of acid decarboxylase (the GABA synthetizing the frog: Bfreotsof bicundliae, auyit#*na and SR 95103. enzyme) immunoreactive axon terminals in the a new GARA antapniat.Etuapean JWMI of Mamadogy, 118, 61-68. pretectal nuclei (Y&XI, Hindeiang, Stoeckel 8t Bcmamturc, N., Jardon, B., Wioland, N., Yiiuel, H. & Bonaventure, 1988), support this hypothesis. Rudolf. 0. (1988). On &oline& me&a* in the On the other hand, microinjections of GABA optokinctk nystagmus of the free: Ansgktr of antagonists into the pretcctum, provoked the muscar& and nicotinic systems. &&x&s& w appearance of a N-T component in the eye Research, 27. 59-7 1.
Horizontal monocular head and eye OKN Caldwell, J. H., Daw, N. W. & Wyatt, H. J. (1978). Etfects of picrotoxin and strychnine on rabbit retinal ganglion cellsz Lateral interactions for cells with more complex recep tive fields. Journal of Physiology (London), 276277-298. Cochran, S. L., Dieringer, N. & Precht, W. (1984). Basic optokinetic ocular reflex pathways in the frog. Joumul of Neuroscience, 4, 43-57. Conover, W. J. (1971). The use of ranks. In Prucriccrlnon pammerric statistics (pp. 203-216). New York: Wiley. Dieringer, N. & Precht, W. (1982). Compensatory head and eye movement in the frog and their contribution to stabilization of gaze. Experimental Brain Research, 47, 394-406. Fukuda, T. (1959). The unidirectionality of the labyrinthinc reflex in relation to the unidirectionality of the optokinetic reflex. Acfo Ofo-Luryngologica, 50, 507-516. Gioanni, H., Rey, J., Villalobos. J. & Dalbera, A. (1984). Single unit activity in the nucleus of the basal optic root (nBOR) during optokinetic, vestibular and visuo-vestibular stimulations in the alert pigeon (Columbia Iiuiu). Experimenral Brain Research, 57, 49-60. Katte, 0. & Hoffinann, K.-P. (1980). Direction specific neurons in the pretectum of the frog (Runu esnrlcnru). Journal of Comparative Physiology, 140, 53-57. Koch, U. T. (1977). A miniature movement detector applied to recording beats in the locusta. Fortschritte &r Zoologie. 24, 327-332.
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Kondrashev. S. L. & Orlov. 0. Y. (1976). Directionsensitive neurons in the frog visual system. Neirojziologie, 8. 196198. Laxar, G.. Alkonyi. B. & Toth, P. (1983). J&-investigation of the role of the accessory optic system and pretectum in the horizontal optokinetic head nystagmus of the frog. Lesion experiments. Acta Biologica Hungarica, 34, 385-393. Montgomery, N.. Fite, K. V., Taylor, M. & Bengston, L. (1982). Neuron correlates of optokinetic nystagmus in the mesencephalon of Rwta pipiens: Functional analysis. Brain Behaviour and Evohuion, 21, 137-153. Sillito, A. M. (1977). Inhibitory processes underlying the directional specificity of simple, complex and hypercomplex cells in the cat’s visual cortex. Journal of Physiology (London), 271. 699-721. Tauber, E. S. & Atkin. A. (1968). Optomotor responses to monocular stimulation: Relation to visual system organixation. Science MO, 1365-1367. YticeJ, Y. H., Hi&huq, C., Stoe&J, hf. E. & Bonavemure, N. (1988). GAD immunoreactivity in pretectal and accessory optic nuclei of the frog mesencephalon. Neuroscience Letters, 84, l-6. Yiicel, Y. H., Jardon, B. and Bonaventure, N. (1989). Involvement of ON and OFF retinal channels in the eye and head horizontal optokinetic nystagmus of the frog. Visual Neuroscience, 5 357-365.
