Readaptation of the vestibuloocular reflex to 1g-Condition in immature lower vertebrates (Xenopus laevis) after micro- or hypergravity exposure

Acta Astronautica

0094~5765(95)00135-2

Vol. 36, Nos 8-12. pp. 487-503, 1995 Copyright 0 1996 Elscvier Science Ltd Printed in Gmt Britain. All rights nscrved

READAPTATION OF THE VESTIBULOOCULAR REFLEX TO lgCONDITION IN IMMATURE LOWER VERTEBRATES (Xenopus Zaevis) AFTER MICRO- OR HYPERGRAVITY EXPOSURE C. Sebastimf, E. Horn’, K. Efkling’ and J. Neubertt ‘Section of Neumphysiology, Department of Neurology, University, Albert-Einstein-Allee II, D - 89081 ULM, Germany ‘Gravitational Biology, Aerospace Medicine Department, DLR, Linder HI%, D - 51140 K&N, Germany

Abstract

The effects of altered gravitational conditions (AGC) on the development of the static vestibulo-ocular reflex O/OR) and readaptation to Ig were investigated in the amphibian Xenopus laevis. Tadpoles were exposed to microgravity (ug) during the German Space Mission D-2 for 10 days, using the STATEX closed survival system, or to 3g for 9 days during earth-bound experiments. At the beginning of AGC, the tadpoles had not yet developed the static VOR. The main results were: (i) Tadpoles with ug- or 3g-experience had a lower gain of the static VOR than the lg-controls during the 2nd and 5th post-AGC days. (ii) Readaptation to response levels of lg-reared controls usually occurred during the following weeks, except in slowly developing tadpoles with 3g-experience. Readaptation was less pronounced if, during the acute VOR test, tadpoles were rolled from the inclined to the normal posture than in the opposite test situation. It is postulated that (i) gravity is necessarily involved in the development of the static VOR, but only during a period including the time before onset of the first behavioural response; and (ii) readaptation which is superimposed by the processes of VOR development depends on many factors including the velocity of development, the actual excitation level of the vestibular systems and the neuroplastic properties of its specific pathways. 487

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1. Introduction Environmental cues play a significant role in the development of sensory systems. Under well defined conditions, modifications of the specific stimulus field or, generally, of the neuronal output of a sensory system cause irreversible as well as reversible physiological or structural changes of the sensory system. Visual deprivation reduced the potency for binocular sensitivity of visual cortex neurons (see [I, 21). Acoustic deprivation blocked the development of the typical tonotopic organization of the acoustic nuclei in the colliculus superior [3]. A sensory deprivation of the tactile system in rodents by exstirpation of their sinus hairs induced an irreversible mal-formation of the barrel organization of neurones within their somatosensory cortex [4]. The period of life with the highest sensitivity for the induction of irreversible physiological and structural alterations was called the “sensitive or critical period” (see [2]). So far, nothing is known about the existence of a critical period in the development of the vestibular system. The deprivation method which is obviously the most critical approach, needs the use of long-term weightlessness conditions. For technical reasons, the realization of this approach was impossible in former times. But since the introduction of space exploration, this technical obstacle was removed and it became possible to expose animals to microgravity (near weightlessness). Furthermore, the vestibular system is characterized by a high potency of neuronal plasticity by which behavioural and physiological defects induced by anatomical or environmental disturbances are compensated for [5]. To investigate in detail the problem of a “sensitive period” for the vestibular system, the first step is to demonstrate the general influence of altered gravitational conditions (AGC) on the functional development. Both, micro- and hypergravity can be used for this approach, but from both only microgravity exposure of animals will give information about the necessity of gravity for the functional development of the vestibular system. To answer the question about the existence of a sensitive period it is necessary to investigate the readaptation to Ig- conditions after a period of AGC. The static vestibulo-ocular reflex (VOR) can be used for this analysis because (i) it is elicited by the stimulatory effect of gravity on the otolith organ; (ii) this response can easily be quantified, and (iii) its development in the amphibian Xenopus laevis was investigated in detail 16, 71. It was also shown in lower vertebrates, that this reflex was affected by a transient exposure to microgravity [8] or to hypergravity [9] and a hypothesis was formulated that altered gravitational condition will become effective if it covers the period at which the VOR appeared for the first

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time [8]. Additionally, the study of the dynamic VOR which is induced by a stimulation of the semicircular canal system offers the possibility, to distinguish between specific gravity induced effects related unequivocally to the otolith organ, and unspecific ones affecting many sensory systems of animals in response to an exposure to AGC.

2. Methods We studied the influence of microgravity and hypergravity exposure on the early development of the VOR in the amphibian Xenopus laevis. To expose animals to microgravity (ug), the tadpoles were transported by means of the STATEX-modul, a closed survival system for the transport of small animals in space [IO], aboard of the space shuttle Columbia during the German space mission D-2 in 1993. Some animals were exposed to microgravity (us), another group was rotated in a centrifuge to simulate the Ig-condition (inflight lg-control, F-lg). At the beginning of the AGC period, the tadpoles were at the developmental stages 33 to 36 (definition of stages, see [l I]). At this age, they had not developed the static VOR which firstly can be seen after hatching at the stages 42 to 43 [6]. During the exposure to AGC, the tadpoles were kept under complete darkness to exclude additional cues for spatial orientation. The space flight lasted 10 days; due to steering manoeuvres, the gravitational force varied between IO-2g and 10-59. During the space flight, a ground Igcontrol (G-lg) was also used. It was placed in a duplicate of the flown STATEX modul which was treated like the modul in space concerning temperature, oxygen supply, numbers of animals, etc. Hypergravity (hg) was produced by centrifugation causing 3g. The first behavioural observation was performed 24 to 30 hrs after termination of the hg- or ugexposure. For the behavioural measurements, the tadpoles were immobilized mechanically within an observation chamber. Both, the static and the dynamic VOR were induced in each animal during an experimentation period of about 20 min. To elicit the static VOR, the observation chamber was rolled in 15” steps once for 360”. The time for the movement from one to the next roll angle lasted 0.5 s; each step was kept constantly for 7.5 s. The compensatory eye responses of the tadpoles were video-taped in their frontal view. During the change of the roll angle, there was always an response overshoot, which adapts within 2 s and maintained at a constant level (Fig. 1). Therefore, all the data presented here, were taken precisely 7 s after the change of the roll angle. The dynamic VOR was induced by moving the tadpole with a frequency of 1 Hz and and amplitude of &I 5” horizontally. The compensatory eye responses of the animals were video-taped in their dorsal view. The angles of the VOR M 16:8,1*-H

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Fig. 1: A schematic presentation of the stimulus application (step function, lower part of the figure) and the response patterns during stimulation (upper plot). Due to the transient overshoot of the response during the roll movement of the machine, the static VOR characteristics were determined for those eye angles which were obtained precisely during the 7th second (x) after initiation of the passive roll.

were determined by a frame-to-frame analysis for 5 complete cycles. Using the Fast Fourier Transformation (FFT), the gain and phase angle of the response with respect to the stimulus were calculated. From each animal, the reflex characteristic was determined, which describes the relation between the roll angle and the angle of the compensatory eye movement, or in a similar way, the gain of the reflex. The characteristics of both eyes were recorded; because there was no significant difference, the mean of the amplitude values recorded from the right and left eye was used for the description of the efficiency of the otolith system. For all experiments in which the animals were exposed to microgravity or hypergravity, the mean response characteristics were calculated. Recordings were taken at different days after termination of the altered gravity exposure to determine the extent of re-adaptation to lg.

3. Results The characteristics of the static VOR were determined for each tadpole after the termination of altered gravity exposure. They were sinusoidal with maximum and minimum eye angles at roll angles between 75” and 120” independent of whether they were recorded from the exposed or from the control groups. These characteristics were used to describe the effects of the altered gravitational field on the static VOR and to analyse also the properties of readaptation. Suitable parameters obtained from

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these characteristics were the peak-to-peak amplitude of the response (amplitude) or the extent of compensatory eye movements for different roll angles which allowed the calculation of the gain by the ratio between the angle of the compensatory eye movement and the roll angle. 3.7. Microgravity 3. I. I. General Effects of Gravity Deprivation (Microgravity). The first recordings of the static VOR were performed 30 hrs after landing of the shuttle Columbia. The period of the experiments lasted 12 days and most of the animals were at the stages 45 and 46 during this period. The median VOR amplitudes obtained from the ug-tadpoles of the developmental stages 45 and 46 were 30.7” and 38.2”, respectively, while for the G-lg tadpoles the corresponding values were 45.6” and 50.8”, respectively. The levels of signifcances were pO.l). Similar results as described for the amplitude of the static VOR were obtained from the observation of the angular eye movements for the roll

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Fig. 2: Amplitude of the static VOR in stage 45 and 46 tadpoles with ugexperience (ug) compared to the inflight and ground lg-controls (F-19 and G-lg, respectively) and in stage 46 and 47 tadpoles with 3g-experience compared to the Ig-reared siblings of the same stock. Recordings of the ug-tadpoles and their Ig-controls were taken between the 2nd and 12th post-flight days. Recordings of the 3g-tadpoles and their lg-controls were taken between the 1st and 3rd post-hg-exposure days. Each dot presents one recording. Columns indicate the median values of the sample; numbers outside the columns represent the numbers of recordings. Bars indicate the standard errors of the medians.

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from the horizontal to the inclined position. Fig. 3, which presents some of’ these results representatively for the roll angles of 75” and QO”, shows this significant increase of the VOR gain from the first to the second recording in the ug-group, while in the ground Ig-control both recordings taken at a seven day interval were at the same level. The gain of the VOR for the movement from the inclined to the horizontal position remained unchanged between the first and second recording during the seven day interval for both the ug-group and the G-lg-group (Fig. 3, right). 3.7.3. No Effects of Microgravity on the Dynamic VOR Tadpoles of the amphibian Xenopus performed compensatory eye movements with a very low amplitude during right-left movements in the horizontal plane. The most pronounced response occurred during stimulation with 1 Hz and the amplitude of &15” for the passive body movement. So far, no significant differences between the gain and phase values recorded from the ug-, F-lg and G-19 tadpoles were found. All tadpoles of the ug-, F-lg- and G-lg-groups performed the dynamic VOR (Fig. 4, left plots). The mean gain values were very low and varied between 0.045 und 0.08. Due to a large interindividual gain variability, the differences between the ug-group and both the inflight and the ground lg-control are not significant (Fig. 4 right, lower plot). The phase angles, i.e. the angular distance between the movement reversal of the eyes with respect to the body showed a significant lead of the eye movement. The mean phase angles recorded for the three experimental groups of tadpoles varied between 45” and 55”; the differences were not significant (Fig. 4 right, upper plot) (see also [12, 131).These recordings showed that ug does not affect the development of the dynamic VOR. Furthermore, the statistical correlation analysis demonstrated that the both types of VOR develop independently. In particular, this analysis showed that, for the tapoles of Xenopus, the gain of the static VOR was not correlated with the gain of the dynamic VOR (1 Hz; &15”) independent of whether the gain of the static VOR for small or large postural changes were used (roll angles 15” or 90’). The correlation coefficients were r=0.15 and 0.2 for the ug-group (n=lQ), r=O.23 and 0.25 for the F-lg-group (n=14) and 1=0.28 and 0.44 for the G-lg-group (n=18), which are all not significant. 3.2. Hypergravity 3.2.7. General Effects of 3g-Exposure The first VOR recordings were taken 24 hrs after termination of the 9 days lasting 3g-exposure. The period of the experiments lasted 11 days.

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Fig. 3: Readaptation to lg-conditions in tadpoles with ug-experience compared to the developmental progress for the static VOR gain in ground lgreared tadpoles of the same strain.The first recordings (white columns) were taken during the 2nd and 5th day after termination of ug condition, while the second recording (hatched columns) were taken 7 days later between the 9th and 12th post-flight day. Dots indicate individual values. Left side: rotation of the animals from the horizontal to the inclined position. Right side: Rotation of the animals from the inclined to the horizontal position (see insets). n.s., non signficant (~~0.2). DV, dorsoventral axis of the tadpoles. The insets show the movement paradigms.

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Fig. 4: Effects of microgravity on the dynamic VOR in the amphibian Xenopus Eaevis.Left: The dynamic VOR recorded for the right and left eyes of a tadpoles with ug-experience and of another tadpole from the ground lg-control. These animals are representative examples, showing their ability to perform the dynamic VOR. The sine-wave between the eye characteristics demonstrate the time course of the stimulus, i.e. the passive right-left movement of the animals at an amplitude of k15” and a frequency of 1 Hz. - Right: Median Values and statistical levels of significances are given for the phase (upper plot) and the gain (lower plot) of the response. For each animal, 5 cycles of a passive left-right movement of the body at a frequency of 1 Hz and an amplitude of &I 5” were used for the calculation of the data.

The animals were at the developmental stages 46 and 47 during this period. Generally, tadpoles with a 9 days lasting 3g-experience showed clear compensatory eye movements during lateral roll as the lg-reared controls of the same strain. In both groups, the response characteristics of the individual animals were sinusoidal with maximal eye deviations from the normal posture at roll angles between 75” and 120”.

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to lg-Conditions

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The VOR amplitudes determined for the 3g-group between the 2nd and 4th day after the end of 3g-exposure were 25.6” for the stage 46 and 26.5” for the stage 47 tadpoles; the corresponding VOR amplitudes for the lg-controls were 34.1’ and 38.5, respectively. The differences were significant at the levels of pdO.01 and pcO.001, respectively (Fig. 2, lower plot). Readaptation to 1g-condition after 3g-exposure was investigated in the 3g-group for both the stage 46 and 47 groups by recording the static VOR for the second time. The same procedure was performed in the lgcontrol to measure the progress of normal VOR development during lgrearing. The second recordings were always taken between the days 8 and 11 after the end of Sg-exposure. Between the first and second measurement, a significant increase of the amplitude of the static VOR occurred. Interestingly, the stage 47 tadpoles but not the stage 46 tadpoles were able to readapt to the level of normal VOR development during the recording period, which was recorded from the Ig-reared group. In particular, during the second recording, the 3g-group of the stage 46 tadpoles had a median VOR amplitude of 28.4”, while the VOR amplitude in the Ig-controls at the same developmental stage amounted to 53.0” (p
4. Discussion 4.1. A Time Window for Gravity Influences on the VOR Development The reduced extent of the static VOR, recorded in Xenopus tadpoles after microgravity or hypergravity exposure, clearly demonstrates that gravitational input is necessary for the normal development of the static VOR. Size reduction or demineralisation of the otoliths were never observed in frogs [14, 151. It is also unlikely that unspecific effects due to AGC were responsible for this weaker response. This was shown by the

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Fig. 5: Readaptation to lg-conditions in tadpoles with 3g-experience compared to the developmental progress for the static VOR gain in the lg-reared siblings of the same strain. Hypergravity exposure of the tadpoles lasted 9 days; at the end of the 3g-stimulation, tadpoles were 11 days old and have developed either to stage 46 (upper plots) or to stage 47 (lower plots). Each dot represents one recording of one tadpole. The tadpoles of the recording period between day 8 and 11 were also tested between the days 1 and 3 post-AGC, while those of the recording period between day 4 to 6 were investigated only once. Columns indicate the median values of the sample; numbers outside the columns represent the numbers of recordings, i.e. the numbers of animals. Bars indicate the standard errors of the medians.

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fact that the dynamic VOR of the same animals was not affected by ugexposure (cf. [I 2, 131; Fig. 4). The decreased gain of the static VOR in the ug- and hg-tadpoles was rather caused by processes outside of the stimulus transducing morphological apparatus, i.e. by processes acting on central neuronal mechanisms. Recently, a failure of microgravity on the static VOR of fishes was described [8]. It was proposed to relate the different effects of microgravity to the first appearence of the static VOR and the onset of the period of gravity deprivation. In fact, while in the tadpoles, the AGC period started before the first appearence of the static VOR (Fig. 2) in the fishes its onset was thereafter [8]. In chickens, exposure of fertilized eggs for 5 days to near-weightlessness caused significant sensitivity changes for the detection of pulsed linear acceleration of chickens at an age of 21 days [16]. This observation supports the hypothesis that gravity is necessary for the normal development of the static VOR. However, the period of sensitivity to AGC is connected to the period before the onset of the behavioural reflex expression. This assumption can be transferred even to the hypergravity influences. In fact, fish youngsters which were exposed to 3g before they could perform their static VOR, so that the period of reflex formation fell into the period of 3g exposure, showed for at least one week a lower level of their static VOR than their lg-reared control siblings

PI. In conclusion, from the observations in tadpoles (Xenopus laevis) (Frg. 2) and in fish youngsters (Oreochromis mossambicus) (see [8, 91) it can be postulated that gravity is necessarily involved in the normal development of the static VOR. But the extent of its influence is strongly coupled to the period of reflex appearence during development. If animals have no reflex experience before onset of AGC, vestibular reflexes will be modified by them (Fig. 6, left plots). If, however, animals have gravity experience concerning the reflex function, the functional development of the vestibular system is independent of the adequate stimulus (Fig. 6, right plots). 4.2. Mechanisms

Involved in Readaptation

to lg-Condition

The development of sensory systems is characterized by the sensitive period. In some instances, changes of the specific field of stimulus during this period causes irreversible changes of the physiological properties of developing neurons or structural changes of their anatomical projections [I - 41. In organisms which are exposed to AGC during their development, the mechanisms of readaptation are superimposed by the processes of sensory development. Therefore, changes during the post-AGC period can only be projected to mechanisms of readaptation if the corresponding

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Long-Term Altered Gravitational Stimulation Is Effective Is Uneffective If It Begins Before If It Begins After the First Appearence of the Static VOR

Age of the Animals [Days; Developmental Stages]

Fig. 6: A working hypothesis: It postulates that altered gravitational conditions (AGC) exert significant influences on the development of the static VOR only, if the animals were exposed to AGC before the first behavioural response emerged. The dark areas indicate the likely range of developmental progress of the response. The bold curve which is included in all the four figures describes the normal development of the vestibular-induced response. ug, microgravity; hg, hypergravity.

data of the lg-controls were taken into account. The present data did not allow to postulate a sensitive period, because the observation period was too short. Usually, the AGC-tadpoles increased their gain of the static VOR approximately to the level of that obtained from the lg-controls. This means, that despite of the long-term disturbance by the AGC, the extent of readaptation is preprogrammed by a rigid set point within the neuronal activity which determines the gain of the static VOR. However, the development of irreversible changes, which will be characterized by maintained incomplete readaptation to the VOR expression of lg-reared tadpolescan not be excluded for two reasons: firstly, the post-AGC observation period was too short, and secondly, only one duration of AGC was used.

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In fact, there was the remarkable observation that tadpoles with a retarded development during 3g-exposure did not show any tendency to readapt to normal developmental levels during a post-AGC period of 11 days (Fig. 5, upper plot). Generally, the vestibular system is characterized by a highly developed neuroplasticity which has led to the phenomenon of “vestibular compensation”, i.e. to a partial or complete disappearence of pathological symptoms induced by labyrinthine lesions (see [5, 171). The gain of the static VOR compensates only partially [18]. Therefore, whether the failure of readaptation in the slowly developing tadpoles points to the existence of a sensitive period or whether it is caused only by a delayed activation of central nervous readaptation mechanisms remains open and makes more ug- and hg-experiments with different durations of the AGC periods necessary. Mechanisms of readaptation can also be related to the specific vestibular pathways. It was described that microgravity and hypergravity induce looping swimming. Both the static VOR and the looping swimming readapt to normal behaviour under lg-conditions and laboratory light exposure. However, the time constants of this readaptation differ considerably. While looping swimming in Xenopus laevis tadpoles disappears within two days [19, 201, the readaptation of the static VOR needs at least one week, and obviously depends on the progress of the developmental processes during the period of altered gravitational environment (Fig. 5). Supposing that the vestibulo-spinal pathway is involved in the regulation of swimming, the time processes of readaptation to 1g conditions resembles those of vestibular compensation. Balance compensation following unilateral labyrinthectomy in Xenopus tadpoles was faster for the swimming behaviour than for the eye posture [21]. It is likely that readaptation to lg-conditions takes advantage of a higher degree of neuronal plasticity in the vestibulo-spinal pathway compared to that in the vestibulo-ocular one. Finally, the mechanisms of readaptation obviously depend on the actual level of arousal. As Fig. 3 demonstrates, ug-tadpoles showed readaptation if they were rotated from the normal to the inclined posture, but readaption was not significant in the acute test situation when these animals were rotated from the inclined to the normal (horjzontal) posture. In conclusion, the processes of readaptation in developing lower vertebrates are based on a multi-component mechanism. The components use not only the developmental progress but also the different neuroplastic properties of specific vestibular pathways as well as the actual state of arousal.

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Acknowlegmenfs. This study was supported by the Deutsche Agentur Mr Raumfahrtangelegenheiten (DARA), grant no. OlQV8925-5 to E. Horn. We thank the crew of the space shuttle Columbia for their excellent job during the mission. We are also grateful to the Bionetics team at Hangar L for technical support at the KSC. The permission for these experiments was given by the Regierungsprasidium in Tubingen (Germany), no. 399.

5. References 1. K.L. Chow , Neuronal changes in the visual system following visual deprivation. In: Central Processing of Visual Information A: lnfegrafive Functions and Comparative Data (R. Jung, ed.) (Handbook of Sensory Physiology Vll/3), pp. 599-627, Springer Verlag, Berlin, Heidelberg, New York, (1973). 2. T.N. Wiesel, Postnatal development of the visual cortex and influence of environment. Nafure 299, 583-597 (7982). 3. D.J. Withington-Wray, K.E. Binns, S.S. Dhanjal, S.G. Brickley and M.J. Keating, The maturation of the superior collicular map of auditory space in the Guinea Pig is disrupted by developmental auditory deprivation. Eur. J. Neurosci. 2, 693-703 (7990). 4. van der Loos and T.A. Woolsey, Somatosensory cortex: structural alterations following early injury to sense organs. Science 779, 395-398 (1973). 5. K.P.Schaefer and D.L. Meyer, Compensation of vestibular lesions. In: Vesfibular System, Part 2: Psychophysics, Applied Aspects and Genera/ lnferprefafions (H.H. Kornhuber, ed.), pp. 463490, Springer Verlag, Berlin, Heidelberg, New York (1974). 6. E. Horn, H.G. Lang and B. Rayer, The development of the static vestibulo-ocular reflex in the Southern Clawed Toad, Xenopus laevis. I. Intact animals. J. Comp. Physiol. 759, 869-878 (7986a). 7. E. Horn, R. Mack and H.G. Lang, The development of the static vestibule-ocular reflex in the Southern Clawed Toad, Xenopus laevis. II. Animals with acute vestibular lesions. J. Comp. Physiol. 759, 879-885 (7986b). 8. E. Horn, C. Sebastian, K. E13elingand J. Neubert, The static vestibuloocular reflex in lower vertebrates after a transient gravity deprivation during an early period of life. NafurWssenschaffen (in press) (7995).

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9. E. Horn, C. Sebastian, K. EBering, H. Rahmann, K. Slenzka, J. Neubert, W. Briegleb and A. Schatz, Effects of a transient change of the gravitational force on the development of the static vestibuloocular reflex in a fish. Proc 5th Eur. Symp. Life Sci. Res. Space, ESA SP-366, pp. 383386 (1994). 10. J. Neubert, W. Briegleb and A. Schatz, Embryonic development the vertebrate gravity receptors. Nafurwissenschaf?en 76, 428-430 (7 986).

of

11. P.D. Nieuwkoop and J. Faber, Normal Table of Xenopus laevis (Daudin). North Holland Publ. Co., Amsterdam (1967). 12. K. EI3eling, C. Sebastian, J. Neubert and E. Horn, Independent functional development of the vestibular acceleration detectors in young tadpoles (Xenopus laevis). Eur. J. Neurosci. Suppl. 7, 278 (1994a). 13. K. Eaeling, C. Sebastian, J. Neubert and E. Horn, Divergent effects of near weightlessness on the static and dynamic reflex in tadpoles, failure of effects in fish youngsters. In: GGttingen Neurobiology Report 1994 (N. Elsner and H. Breer, eds.), p. 399, Georg Thieme Verlag, Stuttgart, New York (1994b). 14. J.A. Vinnikov, O.G. Gazenko, D.V. Lychakov and L.R. Palmbach, Formation of the vestibular apparatus in weightlessness. In: Development of auditory and vesfibular systems (R. Romand, ed.), pp. 537-560, Academic Press, New York, London, Paris (1983). 15. W. Briegleb, J. Neubert, A. Schatz and B. Kruse, Light microscopic analysis of the graviceptor in Xenu larvae developed in hypogravity. Adv. Space Res. 9, 241-244 (1989). 16. T.A. Jones, J. Vellinger, P.Y. Hester and C. Fermin, Weightlessness and the ontogeny of vestibular function: evidence for persistent vestibular threshold shifts in chicks incubated in space. Physiologisf 34, S743-S144 (1991). 17. W. Precht, Characteristics of vestibular neurons after acute and chronic labyrinthine destruction. In: Vesfibular System, Part 2: Psychophysics, Applied Aspects and General lnfetprefafions (H . H . Kornhuber, ed.) (Handbook of Sensory Physiology, Vol. Vl/2), pp. 451462, Springer Verlag, Berlin, Heidelberg, New York (1974). 18. B. Rayer and E. Horn, The development of the static vestibulo-ocular reflex in the Southern Clawed Toad, Xenopus laevis. Ill. Chronic hemilabyrinthectomized tadpoles. J. Comp. Physiol. l59A, 887-895 (1986).

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19. J. Neubert, W. Briegleb, A. Schatz, I. Hertwig and B. Kruse, The response of structure and function of the gravireceptor in a vertebrate to near weightlessness. Ada Astronautica 771257-262 (7988). 20. J. Neubert, H. Rahmann, W. Briegleb, K. Slenzka, A. Schatz and B. Bromeis, STATEX II on Spacelab Mission D2 - an overview of the joint project “Gravity perception and neuronal plasticity” and preliminary preflight results. Microgravity Q. 1, 773-182 (7997). 21. B. Rayer, E. Cagol and E. Horn, Compensation of vestibular -induced deficits in relation to the development of the Southern Clawed Toad, Xenopus laevis Daudin. J. Comp. Physiol. 757, 487-498 (1983).

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