Function of otolith organ in goldfish revealed from analysis of eye movement induced by acceleration.

An otolith organ on ground behave as a detector of both gravity and linear acceleration, and play an important role in controlling posture and eye movement for tilt of the head or translational motion. On the other hand, a gravitational acceleration ingredient to an otolith organ disappears in microgravity environment. However, linear acceleration can be received by otolith organ and produce a sensation that is different from that on Earth. It is suggested that in microgravity signal from the otolith organ may cause abnormality of posture control and eye movement. Therefore, the central nervous system may re-interprets all output from the otolith organ to indicate linear motion. A study of eye movement has been done a lot as one of a reflection related to an otolith organ system. In this study, we examined function of otolith organ in goldfish revealed from analysis of eye movement induced by linear acceleration or the tilt of body. We analyzed both torsional and vertical eye movements from video images frame by frame. For tilting stimulation, torsional eye movements induced by head down was larger than that induced by head up for larger tilt angle than 30 degrees. In the case of linear acceleration below 0.4 G, however, no clear differences were observed in both torsional and vertical eye movement. These results suggest that body tilt and linear acceleration may not be with equivalent stimulation to cause eye movement on the ground.     

Effects of linear acceleration on fish behavior and eye movements.

Behavioral responses and eye movements of fish during linear acceleration were reviewed. It is known that displacement of otoliths in the inner ear leads to body movements and/or eye movements. On the ground, the utriculus of the vestibular system is stimulated by otolith displacement caused by gravitational and inertial forces during horizontal acceleration of whole body. When the acceleration is imposed on the fish's longitudinal axis, the fish showed nose-down and nose-up posture for tailward and noseward displacement of otolith respectively. These responses were understood that the fish aligned his longitudinal body axis in a plane perpendicular to the direction of resultant force vector acting on the otoliths. When the acceleration was sideward, the fish rolled around his longitudinal body axis so that his back was tilted against the direction in which the inertial force acted on the otoliths. Linear acceleration applied to fish's longitudinal body axis evoked torsional eye movement. Direction of torsion coincided with the direction of acceleration, which compensate the change of resultant force vector produced by linear acceleration and gravity. Torsional movement of left and right eye coordinated with each other. In normal fish, both sinusoidal and rectangular acceleration of 0.1G could evoke clear eye torsion. Though the amplitude of response increased with increasing magnitude of acceleration up to 0.5 G, the torsion angle did not fully compensate the angle calculated from gravity and linear acceleration. Removal of the otolith on one side reduced the response amplitude of both eyes. The torsion angle evoked by rectangular acceleration was smaller than that evoked by sinusoidal acceleration in both normal and unilaterally labyrinthectomized fish. These results suggest that eye torsion of fish include both static and dynamic components.     

Eye movements of goldfish depending on the relationship between acceleration vector and otolith organ.

Prior experiments demonstrated that the acceleration deviating 15 degrees to the right (left) from the longitudinal body axis could not produce vertical eye movement in left (right) eye of the goldfish. From these results, we expected that vertical eye movement of goldfish for the acceleration perpendicular to the longitudinal body axis might different between right and left eye. However, in this experiments, there were no clear difference in magnitude of vertical eye movements for the acceleration shifted 15 degrees around the left-right body axis. On the other hand, the response of right eye was larger than that of left eye for the acceleration applied from left to right of the body. These results suggest that stimulation from medial to lateral and lateral to medial of the otolith organ has different effect on vertical eye movement in each eye of goldfish.     

Studies on spatial orientation and posture control and changes in otolith function due to linear acceleration loading.

Otolith function is directly affected by weightlessness at the time of movement in outer space, and changes occur in the mode of response. It has been known for some time that such changes occur in the posture and gait of astronauts just after they return from a trip into space. It is thought that the cause of these changes is disuse atrophy of the antigravity muscles. However, in the present study, experimental subjects underwent repeated linear acceleration loading over a long period of time, and instability of the head and a decrease in posture control, especially in relation to the gait, were observed for the first time. To date, it has been said that the otolith function has a close relationship with ocular counter rolling. However, when the otolith organ was stimulated, the response was seen to be head instability and an irregular effect on the gait. It is surmised that these findings will facilitate future research into the otolith function under gravity-free conditions.     

A linear canal-otolith interaction model to describe the human vestibulo-ocular reflex

A control systems model of the vestibulo-ocular reflex (VOR) originally derived for yaw rotation about an eccentric axis (Crane et al. 1997) was applied to data collected during ambulation and dynamic posturography. The model incorporates a linear summation of an otolith response due to head translation scaled by target distance, adding to a semi-circular canal response that depends only on angular head rotation. The results of the model were compared with human experimental data by supplying head angular velocity as determined by magnetic search coil recording as the input for the canal branch of the model and supplying linear acceleration as determined by flux gate magnetometer measurements of otolith position. The model was fit to data by determining otolith weighting that enabled the model to best fit the data. We fit to the model experimental data from normal subjects who were: standing quietly, walking, running, or making active sinusoidal head movements. We also fit data obtained during dynamic posturography tasks of: standing on a platform sliding in a horizontal plane at 0.2 Hz, standing directly on a platform tilting at 0.1 Hz, and standing on the tilting platform buffered by a 5-cm thick foam rubber cushion. Each task was done with the subject attending a target approximately 500, 100, or 50 cm distant, both in light and darkness. The model accurately predicted the observed VOR response during each test. Greater otolith weighting was required for near targets for nearly all activities, consistent with weights for the otolith component found in previous studies employing imposed rotations. The only exceptions were for vertical axis motion during standing, sliding, and tilting when the platform was buffered with foam rubber. In the horizontal axis, the model always fit near target data better with a higher otolith component. Otolith weights were similar with the target visible and in darkness. The model predicts eye movement during both passive whole-body rotation and free head movement in space implying that the VOR is controlled by a similar mechanism during both situations. Factors such as vision, proprioception, and efference copy that are available during head free motion but not during whole-body rotation are probably not important to gaze stabilization during ambulation and postural stabilizing movement. The linearity of the canal-otolith interaction was tested by re-analysis of the whole body rotation data on which the model is based (Crane et al. 1997). Normalized otolith-mediated gain enhancement was determined for each axis of rotation. This analysis uncovered minor non-linearities in the canal-otolith interaction at frequencies above 1.6 Hz and when the axis of rotation was posterior to the head. Received: 11 March 1998 / Received in revised form: 1 March 1999     

Three-dimensional head angular velocity detection from otolith afferent signals

Afferent signals from the otolith organs can produce compensatory eye position and velocity signals which has been described as linear vestibulo-ocular reflex (LVOR). The afferent otolith signals carry information about head orientation and changes of head orientation relative to gravity. A head orientation (tilt) related position signal can be obtained from population vector coding of tonic otolith afferent signals during static or dynamic head tilts, which in turn could produce compensatory eye position signals in the LVOR. On the other hand, eye angular velocity signals may be extracted, as proposed in this study, from the population response of tilt-velocity sensitive otolith afferents. Such afferents are shown to encode instantaneous head orientation relative to gravity at onset of a head movement and, as the movement continues, the projection of head angular velocity onto the earth-horizontal plane, indicating the instantaneous direction of movement relative to gravity. Angular velocity components along the earth-vertical direction which are not directly encoded by otolith afferents can be detected by central signal processing. Central reconstruction of 3D head angular velocity allows to obtain information about absolute head orientation in space even in the absence of semicircular canal related information. Such information is important for generating compensatory eye movements as well as for dynamic control of posture.     

Effect of active head movements about the pitch, roll, and yaw axes on human optokinetic afternystagmus

Effects of active head movements about the pitch, roll, or yaw axes on horizontal optokinetic afternystagmas (OKAN) were examined in 16 subjects to test the hypothesis that otolith organ mediated activity induced by a change in head position can couple to the horizontal velocity storage in humans. Active head movements about the pitch axis, forwards or backwards, produced significant OKAN suppression. Pitch forward head movements exerted the strongest effect. Active head movements about the roll axis towards the right also produced OKAN suppression but only if the tilted position was sustained. No suppression was observed following sustained yaw. However, an unsustained yaw left movement after rightward drum rotation significantly enhanced OKAN. Sustained head movement trials did not significantly alter subsequent control trials. In contrast, unsustained movements about the pitch axis, which involve more complex interactions, exerted long-term effects on subsequent control trials. We conclude that otolith organ mediated activity arising from pitch or roll head movements couples to the horizontal velocity storage in humans, thereby suppressing ongoing OKAN. Activity arising from the horizontal canals during an unsustained yaw movement (observed mainly with yaw left), following drum rotation in a direction contralateral to the movement, may also couple to the velocity storage, resulting in increased activity instead of suppression.     

Motor function in microgravity: movement in weightlessness

Microgravity provides unique, though experimentally challenging, opportunities to study motor control. A traditional research focus has been the effects of linear acceleration on vestibular responses to angular acceleration. Evidence is accumulating that the high-frequency vestibulo-ocular reflex (VOR) is not affected by transitions from a 1 g linear force field to microgravity (<1 g); however, it appears that the three-dimensional organization of the VOR is dependent on gravitoinertial force levels. Some of the observed effects of microgravity on head and arm movement control appear to depend on the previously undetected inputs of cervical and brachial proprioception, which change almost immediately in response to alterations in background force levels. Recent studies of post-flight disturbances of posture and locomotion are revealing sensorimotor mechanisms that adjust over periods ranging from hours to weeks.     

A model of the nystagmus induced by off vertical axis rotation

A three-dimensional model is proposed that accounts for a number of phenomena attributed to the otoliths. It is constructed by extending and modifying a model of vestibular velocity storage. It is proposed that the otolith information about the orientation of the head to gravity changes the time constant of vestibular responses by modulating the gain of the velocity storage feedback loop. It is further proposed that the otolith signals, such as those that generate L-nystagmus (linear acceleration induced nystagmus), are partially coupled to the vestibular system via the velocity storage integrator. The combination of these two hypotheses suggests that a vestibular neural mechanism exists that performs correlation in the mathematical sense which is multiplication followed by integration. The multiplication is performed by the otolith modulation of the velocity storage feedback loop gain and the integration is performed by the velocity storage mechanism itself. Correlation allows calculation of the degree to which two signals are related and in this context provides a simple method of determining head angular velocity from the components of linear acceleration induced by off-vertical axis rotation. Correlation accounts for the otolith supplementation of the VOR and the sustained nystagmus generated by off-vertical axis rotation. The model also predicts the cross-coupling of horizontal and vertical optokinetic afternystagmus that occurs in head-lateral positions and the reported effects of tilt on vestibular responses.     

The cerebellar nodulus/uvula integrates otolith signals for the translational vestibulo-ocular reflex

BACKGROUND: The otolith-driven translational vestibulo-ocular reflex (tVOR) generates compensatory eye movements to linear head accelerations. Studies in humans indicate that the cerebellum plays a critical role in the neural control of the tVOR, but little is known about mechanisms of this control or the functions of specific cerebellar structures. Here, we chose to investigate the contribution of the nodulus and uvula, which have been shown by prior studies to be involved in the processing of otolith signals in other contexts. METHODOLOGY/PRINCIPAL FINDINGS: We recorded eye movements in two rhesus monkeys during steps of linear motion along the interaural axis before and after surgical lesions of the cerebellar uvula and nodulus. The lesions strikingly reduced eye velocity during constant-velocity motion but had only a small effect on the response to initial head acceleration. We fit eye velocity to a linear combination of head acceleration and velocity and to a dynamic mathematical model of the tVOR that incorporated a specific integrator of head acceleration. Based on parameter optimization, the lesion decreased the gain of the pathway containing this new integrator by 62%. The component of eye velocity that depended directly on head acceleration changed little (gain decrease of 13%). In a final set of simulations, we compared our data to the predictions of previous models of the tVOR, none of which could account for our experimental findings. CONCLUSIONS/ SIGNIFICANCE: Our results provide new and important information regarding the neural control of the tVOR. Specifically, they point to a key role for the cerebellar nodulus and uvula in the mathematical integration of afferent linear head acceleration signals. This function is likely to be critical not only for the tVOR but also for the otolith-mediated reflexes that control posture and balance.     

Interaction of the angular and linear components of the horizontal vestibulo-ocular reflex in the pigeon

Pigeons were exposed to centric and eccentric horizontal rotations in darkness by velocity trapezoid. Different in sign the duration alterations of the opposite directed horizontal eye nystagmus occurred during otolith membrane shifts in sagittal as well as frontal planes. A direct dependence was found between the duration alterations of the primary nystagmus phase and the peak value alterations of its slow phase velocity under increased (but not decreased) centrifugal force. In the both cases, if duration of the primary nystagmus phase was enlarged, duration of its secondary phase was diminished and vice versa. It suggests the otolith component does not decay up to zero by constant velocity and at once after rotation; by deceleration it is biphasic. In affirms the own hypothesis that the linear component is asymmetric central neuronal activity that modifies the canal component even if this activity by itself is not enough for eye movement initiation.     

Sensory convergence solves a motion ambiguity problem

Our inner ear is equipped with a set of linear accelerometers, the otolith organs, that sense the inertial accelerations experienced during self-motion. However, as Einstein pointed out nearly a century ago, this signal would by itself be insufficient to detect our real movement, because gravity, another form of linear acceleration, and self-motion are sensed identically by otolith afferents. To deal with this ambiguity, it was proposed that neural populations in the pons and midline cerebellum compute an independent, internal estimate of gravity using signals arising from the vestibular rotation sensors, the semicircular canals. This hypothesis, regarding a causal relationship between firing rates and postulated sensory contributions to inertial motion estimation, has been directly tested here by recording neural activities before and after inactivation of the semicircular canals. We show that, unlike cells in normal animals, the gravity component of neural responses was nearly absent in canal-inactivated animals. We conclude that, through integration of temporally matched, multimodal information, neurons derive the mathematical signals predicted by the equations describing the physics of the outside world.     

Stimulus dependence of the development of the zebrafish (Danio rerio) vestibular system

ABSTRACT: It has been suggested that stimulus dependence is a general feature of all developing sensory systems. We tested this idea for the developing zebrafish vestibular system using a bioreactor the National Aeronautic and Space Agency designed to simulate microgravity for cells in culture on earth. We replaced the culture medium with aquarium water and maintained zebrafish eggs/hatchlings in the bioreactor for either 72 or 96 h postfertilization. These experimental animals displayed a swimming behavior that was indistinguishable from the control animals when illuminated from above. However, when illuminated from below, experimental animals swam not only dorsal surface up, but also lying on their side; they corkscrewed, swam vertical loops, and occasionally even swam upside down. When incubated in the bioreactor for 96 h, the saccular otolith was significantly smaller than normal, suggesting that otolith development was either delayed or slower than normal. When incubated in the bioreactor for 72 h, some animals were missing one or more otoliths. In contrast, control animals all had two otoliths on each side. This supports the idea that otolith development was delayed. Immediately upon removal from the bioreactor at 96 h, experimental animals showed some signs of compensatory eye rotation, but with a much less clear relationship between the orientation of the eye and the direction of gravity than the age-matched control animals. This difference was still obvious 1 day later. These results support the idea that development of the vestibular system in zebrafish is dependent on the presence of the normal stimulus the system is designed to detect.     

The Temporal Structure of Vertical Arm Movements

The present study investigates how the CNS deals with the omnipresent force of gravity during arm motor planning. Previous studies have reported direction-dependent kinematic differences in the vertical plane; notably, acceleration duration was greater during a downward than an upward arm movement. Although the analysis of acceleration and deceleration phases has permitted to explore the integration of gravity force, further investigation is necessary to conclude whether feedforward or feedback control processes are at the origin of this incorporation. We considered that a more detailed analysis of the temporal features of vertical arm movements could provide additional information about gravity force integration into the motor planning. Eight subjects performed single joint vertical arm movements (45° rotation around the shoulder joint) in two opposite directions (upwards and downwards) and at three different speeds (slow, natural and fast). We calculated different parameters of hand acceleration profiles: movement duration (MD), duration to peak acceleration (D PA), duration from peak acceleration to peak velocity (D PA-PV), duration from peak velocity to peak deceleration (D PV-PD), duration from peak deceleration to the movement end (D PD-End), acceleration duration (AD), deceleration duration (DD), peak acceleration (PA), peak velocity (PV), and peak deceleration (PD). While movement durations and amplitudes were similar for upward and downward movements, the temporal structure of acceleration profiles differed between the two directions. More specifically, subjects performed upward movements faster than downward movements; these direction-dependent asymmetries appeared early in the movement (i.e., before PA) and lasted until the moment of PD. Additionally, PA and PV were greater for upward than downward movements. Movement speed also changed the temporal structure of acceleration profiles. The effect of speed and direction on the form of acceleration profiles is consistent with the premise that the CNS optimises motor commands with respect to both gravitational and inertial constraints.     

Studies on vestibular organs in the fry of mutant Medaka.

We provide an overview of the features of vestibular organs, especially of otolith organs in mutant Medaka ha. The ha fish have a dysfunction in sensing gravity due to the absence of utricular otoliths either unilaterally or bilaterally. Especially in their early developmental stages, the posture control is predominantly depend on light rather than on gravity seen in the wild-type. The ha juveniles that were kept and tolerated in an environment with altered light directions indicated a strong light dependency on the posture maintenance, while the fish under an ordinary light environment gradually changed their posture control by sensing light to gravity around 30 days after hatching and beyond. Their behavior under microgravity agreed with such phenomena observed in ground laboratory.     

Apoptosis controls the speed of looping morphogenesis in Drosophila male terminalia

In metazoan development, the precise mechanisms that regulate the completion of morphogenesis according to a developmental timetable remain elusive. The Drosophila male terminalia is an asymmetric looping organ; the internal genitalia (spermiduct) loops dextrally around the hindgut. Mutants for apoptotic signaling have an orientation defect of their male terminalia, indicating that apoptosis contributes to the looping morphogenesis. However, the physiological roles of apoptosis in the looping morphogenesis of male terminalia have been unclear. Here, we show the role of apoptosis in the organogenesis of male terminalia using time-lapse imaging. In normal flies, genitalia rotation accelerated as development proceeded, and completed a full 360° rotation. This acceleration was impaired when the activity of caspases or JNK or PVF/PVR signaling was reduced. Acceleration was induced by two distinct subcompartments of the A8 segment that formed a ring shape and surrounded the male genitalia: the inner ring rotated with the genitalia and the outer ring rotated later, functioning as a 'moving walkway' to accelerate the inner ring rotation. A quantitative analysis combining the use of a FRET-based indicator for caspase activation with single-cell tracking showed that the timing and degree of apoptosis correlated with the movement of the outer ring, and upregulation of the apoptotic signal increased the speed of genital rotation. Therefore, apoptosis coordinates the outer ring movement that drives the acceleration of genitalia rotation, thereby enabling the complete morphogenesis of male genitalia within a limited developmental time frame.     

Functional asymmetry estimated by measurements of otolith in fish.

It is widely accepted that the incidence of space adaptation syndrome (SAS) is due to a mismatch of sensory information from various receptors to the central nervous system. We investigated the functional asymmetry of vestibular organ, which may caused sensory conflict in space, by measuring the weight difference of otolith between left and right side in goldfish and carp. In the goldfish utricular otolith, the maximum difference was 0.8 mg and the mean difference was 0.091 mg. The percentage of weight difference to the heavier otolith was calculated. The maximum difference was 20.57% and the mean was 3.035%. A difference exceeding 10% was found in only 2 goldfish. In the carp utricular otolith, the maximum percentage difference of weight was 24.8% and the mean was 3.491%. A difference exceeding 10% was found in only 3 carp. The maximum difference of saccular otolith was 11.8% with the mean of 6.92%, and that of lagenar otolith was 32% with the mean of 5.6% in goldfish. The close relationship of utricular otolith weight between both sides suggested that the otolith asymmetry might not be the main factor inducing SAS at least in goldfish and carp.     

Cross axis VOR induced by pursuit training in monkeys: further properties of adaptive responses

We have shown recently in alert monkeys that repeated interaction between the pursuit and vestibular systems in the orthogonal plane induces adaptive changes in the VOR. To examine further properties of adaptive cross axis VOR induced by pursuit training, sinusoidal whole body rotation was applied either in the pitch or yaw plane while presenting a target spot that moved orthogonally to the rotation plane with either 90 degrees phase-lead or 90 degrees phase-lag to the chair signal. After one hour of training at 0.5 Hz (+/- 10 degrees), considerable phase-shift was observed in orthogonal eye movement responses consistent with the training paradigms by identical chair rotation in complete darkness, with further lead at lower frequencies and lag at higher frequencies. However, gains (eye/chair) induced by phase- shift pursuit training was different during pitch and yaw rotation. Although frequency tuning was maintained during pitch in the phase-shift paradigms, it was not maintained during yaw, resulting in higher gains at lower stimulus frequencies compared to the gains during yaw. This difference may reflect otolith contribution during pitch rotation. To understand further the nature of signals that induce adaptive cross axis VOR, we examined interaction of pursuit, whole field-visual pattern and vestibular stimuli. Magnitudes of the cross axis VOR with a spot alone on one hand and with a spot and pattern moving together in the same plane on the other during chair rotation were similar, and when one of the two visual stimuli was stationary during chair rotation, our well trained monkeys did not induce the cross axis VOR. These results suggest that the cross axis VOR induced by pursuit training shares common mechanisms with the cross axis VOR induced by whole field-slip stimuli and that if conflicting information is given between the two visual stimuli, adaptive changes are inhibited. Horizontal GVPs were recorded in the cerebellar floccular lobe during pitch rotation coupled with horizontal pursuit stimuli. These GVPs did not respond to pitch in the dark before training, but responded after 60 min of pursuit training with eye velocity sensitivities similar to those before training. Adaptive change in the VOR was specific to smooth eye movements but not to saccades in our paradigms.     

Eye movements of flatfish for the changes of gravity (II)

In this study, we analysed the eye movements of flatfish for body tilting and compared with that of goldfish. The fish was fixed on the tilting table controlled by computer. The eye movements for body tilting along the different body axis were video-recorded. The vertical and torsional eye rotations were analysed frame by frame. In normal flatfish, vertical eye movement of left eye to leftward tilting was larger than that to rightward tilting. For head up or head down tilting, clear vertical eye movements were observed. On the other hand, torsional eye movements showed similar characteristics as goldfish. These results suggested that sacculus and lagena were important for otolith-ocular eye movements in flatfish.     

Asymmetries in the sense organs and central nervous system of the squid Histioteuthis

The visual system of Histioteuthis is markedly asymmetrical, in that the eyes and optic lobes are considerably larger on the left side, and the lens of the left eye is often yellower in colour than that of the right eye. At the histological level, the rhabdomes of the retinas of both eyes show the usual rectilinear pattern typical of cephalopods. Unlike other species described, however, the orientation of the pattern is not uniform over the retina. The optic lobes are well developed on both sides, again following the typical squid pattern, although the plexiform and inner granular layers are thicker on the left side. In life it is likely that the animals orient at an oblique angle with the arms downward, and the left eye pointing upwards and the right eye downwards, and the asymmetries of the visual system are probably related to this posture. No corresponding asymmetries in the statocysts or other parts of the central nervous system have, however, been detected