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We have reported that calretinin and calbindin staining of calyxes in the apical region of the cristae is reduced or absent in old gerbils (>or=35 months) that had normal numbers of hair cells [Kevetter GA, Leonard RB (2002) Decreased expression of calretinin and calbindin in the labyrinth of old gerbils. Brain Res 957:362-365]. Here we examine the ability of primary afferents in aged gerbils to carry a tracer injected into the vestibular nuclear complex to their terminals in the cristae. Calyxes throughout the cristae were well labeled in a young animal with such an injection. In the aged animals, many calyxes were only partially filled or not filled at all. In some cases labeled axons were also missing from the stroma underlying the missing calyxes. There is a strong correspondence between the region where the calyxes were not filled and the absence of calretinin immunostaining. To determine if afferents from the cristae are functionally abnormal, we recorded from their axons and attempted to activate them with natural stimulation. Among afferents that could be activated, we encountered many afferents that had spontaneous activity but could not be modulated with natural stimulation. When tested, the firing rate of these afferents could be modulated with galvanic stimulation, and/or they could be activated by pulsed electrical stimulation. We also encountered afferents that had no spontaneous activity. The presence of these axons was revealed by an injury discharge that could not be modulated with natural stimulation. When tested, these axons could be activated with pulsed electrical stimulation. In some instances we encountered two or more such afferents in a row, an event we have not seen in young animals. We suggest that the simplest explanation for these observations is that calyxes are being lost in old animals.

The function of semicircular canals (SC) is based on the precise equality of densities of the cupula and endolymph. Otherwise the information provided by SC would depend on the orientation of both the gravity vector relative to canal plane and the axis of rotation. It would also depend on the distance between the axis of rotation and the center of the SC. We believe that the equality of densities is approximate and expect that due to the high sensitivity of the SC, even the small differences of densities (approximately 10(-4) g/cm3) can influence the SC dynamics, and this influence depends on the conditions of canal stimulation. The work aims to examine this hypothesis and analyze the parameters of the SC and mechanical stimulation under which the effect of the difference of densities on the SC functioning could be observed.

The ability to orient and navigate through the terrestrial environment represents a computational challenge common to all vertebrates. It arises because motion sensors in the inner ear, the otolith organs, and the semicircular canals transduce self-motion in an egocentric reference frame. As a result, vestibular afferent information reaching the brain is inappropriate for coding our own motion and orientation relative to the outside world. Here we show that cerebellar cortical neuron activity in vermal lobules 9 and 10 reflects the critical computations of transforming head-centered vestibular afferent information into earth-referenced self-motion and spatial orientation signals. Unlike vestibular and deep cerebellar nuclei neurons, where a mixture of responses was observed, Purkinje cells represent a homogeneous population that encodes inertial motion. They carry the earth-horizontal component of a spatially transformed and temporally integrated rotation signal from the semicircular canals, which is critical for computing head attitude, thus isolating inertial linear accelerations during navigation.

We are developing prosthetics for patients suffering from peripheral vestibular dysfunction. We tested a sensory-replacement prosthesis that stimulates neurons innervating the vestibular system by providing chronic pulsatile stimulation to electrodes placed in monkeys' lateral semicircular canals, which were plugged bilaterally, and used head angular velocity to modulate the current pulse rate. As an encouraging finding, we observed vestibulo-ocular reflexes that continued to be evoked by the motion-modulated stimulation months after the nystagmus evoked by the constant-rate baseline stimulation had dissipated. This suggests that long-term functional replacement of absent vestibular function is feasible.

Purpose: With the head upright and stationary, ocular torsion is confined by Listing's Law (LL), so that three-dimensional eye rotational axes form Listing's plane (LP). During head rotation, the vestibulo-ocular reflex violates LL by driving ocular torsion opposite to head torsion, sometimes out of LP. Saccades originating from non-Listing's initial torsional positions remain in a plane offset from, but parallel to, the original LP. The present study was conducted to determine whether whole-body yaw alters the position and orientation of LP., Methods: Eight normal subjects and six with unilateral vestibular deafferentation (UVD) underwent binocular eye and head movement recordings with 3-D magnetic search coils. Visual fixations were used to define LP, after which subjects underwent whole-body yaw rotation of 30 degrees or 70 degrees , at peak accelerations from 125 deg/s(2) to 2800 deg/s(2). Gaze during rotation was either central or 20 degrees up. After rotation, a dynamic LP (DLP) was defined during fixations., Results: Orientation and thickness of the DLP did not vary significantly from the previously defined LP; however, DLP was offset an average of 4 degrees +/- 4 degrees (mean +/- SD), 87% of head torsion relative to LP. Stimulus intensity, UVD, and starting vertical gaze direction had no effect on DLP offset or orientation. The DLP torsional offset declined toward the original LP with a time constant of approximately 1 minute, suggesting mediation by neural integration., Conclusions: Yaw rotation can cause stable torsional offsets in the location of Listing's Plane.

Introduction: Vestibular activation of semicircular canals has been linked to increased activity of parasympathetic neurons and has been proposed as a contributing factor to orthostatic intolerance. However, the functional consequences of head yaw rotation during orthostasis on human autonomic function have not been documented. The purpose of this study was to determine the effects of voluntary head rotation on autonomic function during upright tilt., Methods: ECG, beat-by-beat finger arterial pressure, respiratory rate, PetCO2, and cerebral blood flow velocity were recorded in 10 healthy subjects. Subjects were studied supine and during two separate 5-min periods of upright tilt to 70 degrees with and without continuous head yaw rotation (180 degrees at 0.25 Hz). Breathing frequency was controlled strictly at 0.25 Hz during each trial and data were analyzed in both time and frequency domains. Cross-spectral techniques (transfer functions) were used to assess cardiovagal baroreflex sensitivity and dynamic cerebral autoregulation., Results: Head rotation during upright tilt increased transfer function magnitude between systolic pressure and R-R interval at the low frequency (0.04-0.15 Hz) from 8.1 +/- 2.3 to 10.4 +/- 1.6 ms x mmHg(-1) (p = 0.04), but did not affect estimates of vagal-cardiac efferent activity or cerebral blood flow velocity, hemodynamic oscillations, or dynamic cerebral autoregulation., Conclusions: Increased cardiovagal baroreflex sensitivity in conjunction with preserved cerebral autoregulation suggests that head rotation during upright tilt is unlikely to trigger orthostatic instability in normal, healthy humans.

Central vestibular neurons process head movement-related sensory signals over a wide dynamic range. In the isolated frog whole brain, second-order vestibular neurons were identified by monosynaptic responses after electrical stimulation of individual semicircular canal nerve branches. Neurons were classified as tonic or phasic vestibular neurons based on their different discharge patterns in response to positive current steps. With increasing frequency of sinusoidally modulated current injections, up to 100 Hz, there was a concomitant decrease in the impedance of tonic vestibular neurons. Subthreshold responses as well as spike discharge showed classical low-pass filter-like characteristics with corner frequencies ranging from 5 to 20 Hz. In contrast, the impedance of phasic vestibular neurons was relatively constant over a wider range of frequencies or showed a resonance at approximately 40 Hz. Above spike threshold, single spikes of phasic neurons were synchronized with the sinusoidal stimulation between approximately 20 and 50 Hz, thus showing characteristic bandpass filter-like properties. Both the subthreshold resonance and bandpass filter-like discharge pattern depend on the activation of an I(D) potassium conductance. External current or synaptic stimulation that produced impedance increases (i.e., depolarization in tonic or hyperpolarization in phasic neurons) had opposite and complementary effects on the responses of the two types of neurons. Thus, membrane depolarization by current steps or repetitive synaptic excitation amplified synaptic inputs in tonic vestibular neurons and reduced them in phasic neurons. These differential, opposite membrane response properties render the two neuronal types particularly suitable for either integration (tonic neurons) or signal detection (phasic neurons), respectively, and dampens variations of the resting membrane potential in the latter.

Objectives: Although numerous studies have identified damage to the cochlear and vestibular end organs as the primary site of aminoglycoside-induced ototoxicity, the effect on the saccule remains poorly understood, possibly due to lack of monitoring saccular function in experimental animals. Therefore, this study applied three kinds of aminoglycosides into the tympanic space of guinea pigs to examine their toxic impact on the saccule by way of click-evoked myogenic potential test coupled with morphologic assessment., Design: Albino guinea pigs were treated with saline, gentamicin, tobramycin, or amikacin, with 10 animals assigned to each group. Each compound was injected directly overlying but not through the round window membrane on the left ear, with the right ear serving as a control. One week after injection, each animal underwent auditory brain stem response, caloric test, and click-evoked myogenic potential test. Animals were then killed for morphologic assessment through the use of light and electron microscopic examinations., Results: The animals treated with saline, gentamicin, tobramycin, or amikacin exhibited abnormal auditory brain stem response in 0%, 30%, 100%, and 30% of cases; abnormal caloric responses were found in 0%, 100%, 40%, and 40% of cases; absent click-evoked myogenic potentials were found in 0%, 100%, 30%, and 40% of cases, respectively. Gentamicin and other groups differed significantly in abnormal rates of caloric responses and click-evoked myogenic potentials. Morphologic study of the gentamicin-treated animals confirmed that the absence of click-evoked myogenic potential originated from the lesion in the saccular macula., Conclusions: Gentamicin represents the dominant susceptibility of aminoglycoside-induced vestibulotoxicity for eliminating both semicircular canal and saccular functions. This study further confirms the findings of human studies in which the caloric and vestibular evoked myogenic potentials responses were monitored to assess the abolition of vestibular function in patients treated with intratympanic gentamicin injection.

We investigated the possible contribution of signals carried by vestibular-nerve afferents to long-term processes of vestibular compensation after unilateral labyrinthectomy. Semicircular canal afferents were recorded from the contralesional nerve in three macaque monkeys before [horizontal (HC) = 67, anterior (AC) = 66, posterior (PC) = 50] and 1-12 mo after (HC = 192, AC = 86, PC = 57) lesion. Vestibular responses were evaluated using passive sinusoidal rotations with frequencies of 0.5-15 Hz (20-80 degrees /s) and fast whole-body rotations reaching velocities of 500 degrees /s. Sensitivities to nonvestibular inputs were tested by: 1) comparing responses during active and passive head movements, 2) rotating the body with the head held stationary to activate neck proprioceptors, and 3) encouraging head-restrained animals to attempt to make head movements that resulted in the production of neck torques of < or =2 Nm. Mean resting discharge rate before and after the lesion did not differ for the regular, D (dimorphic)-irregular, or C (calyx)-irregular afferents. In response to passive rotations, afferents showed no change in sensitivity and phase, inhibitory cutoff, and excitatory saturation after unilateral labyrinthectomy. Moreover, head sensitivities were similar during voluntary and passive head rotations and responses were not altered by neck proprioceptive or efference copy signals before or after the lesion. The only significant change was an increase in the proportion of C-irregular units postlesion, accompanied by a decrease in the proportion of regular afferents. Taken together, our findings show that changes in response properties of the vestibular afferent population are not likely to play a major role in the long-term changes associated with compensation after unilateral labyrinthectomy.

This paper presents a biomechanical model of the sensorial cells in otolithic organs and a design of a 3D device that imitates the biological system. Starting from anatomical and physiological data, mechanical and structural parameters have been identified and a mechanical model has been formulated, by considering the cilia and kinocilium as a interconnected structure. The mechanical model was used to simulate the behavior of the system under known conditions. Furthermore, the behavior of a proximal link to the kinocilium were investigated for a better comprehension regarding the polymeric materials that could be used to model and manufacture the biological organs. The results obtained from the models were used to design a biomimetic organ.

Two central, related questions in motor control are 1) how the brain represents movement directions of various effectors like the eyes and head and 2) how it constrains their redundant degrees of freedom. The interstitial nucleus of Cajal (INC) integrates velocity commands from the gaze control system into position signals for three-dimensional eye and head posture. It has been shown that the right INC encodes clockwise (CW)-up and CW-down eye and head components, whereas the left INC encodes counterclockwise (CCW)-up and CCW-down components, similar to the sensitivity directions of the vertical semicircular canals. For the eyes, these canal-like coordinates align with Listing's plane (a behavioral strategy limiting torsion about the gaze axis). By analogy, we predicted that the INC also encodes head orientation in canal-like coordinates, but instead, aligned with the coordinate axes for the Fick strategy (which constrains head torsion). Unilateral stimulation (50 microA, 300 Hz, 200 ms) evoked CW head rotations from the right INC and CCW rotations from the left INC, with variable vertical components. The observed axes of head rotation were consistent with a canal-like coordinate system. Moreover, as predicted, these axes remained fixed in the head, rotating with initial head orientation like the horizontal and torsional axes of a Fick coordinate system. This suggests that the head is ordinarily constrained to zero torsion in Fick coordinates by equally activating CW/CCW populations of neurons in the right/left INC. These data support a simple mechanism for controlling head orientation through the alignment of brain stem neural coordinates with natural behavioral constraints.

The vestibular function was investigated in 13 Russian crew members of the ISS missions on days 1(2), 4(5), and 8(9) after prolonged exposure to microgravity (126 to 195 days). The static torsional otolith-cervico-ocular reflex was studied, as well as the dynamic vestibulo-cervico-ocular responses, vestibular reactivity, and spontaneous oculomotor activity using videooculography (VOG) and electrooculography (EOG) for simultaneous recording of eye movements. On days 1-2 of return to the gravity (R+1-2), the cosmonauts were found to increase the spontaneous oculomotor activity (floating eye movements, both typical and atypical forms of spontaneous nystagmus, square wave jerks, gaze nystagmus) with the head held in the vertical position. The otolith function during static head inclinations to the right or left shoulder at 30 degrees was suppressed as determined by the inversion or absence, or reduction by half of the amplitude of torsional compensatory eye counter-rolling and the vestibular reactivity during head yaw movements at 0.125 Hz was increased as revealed by a lowered threshold and an increased intensity of vestibular nystagmus. The pattern, depth, dynamics, and velocity of the vestibular function recovery varied with individual participants in the investigation. However, the suppressed otolith functioning in the period of readaptation to the normal gravity was, as a rule, accompanied by an exaggerated vestibular reactivity.

Vestibular evoked myogenic potentials (VEMP) in response to sound stimulation (500 Hz tone burst, 129 dB SPL) were studied in 1000 consecutive patients. VEMP from the ear with the larger amplitude were evaluated based on the assumption that the majority of the tested patients probably had normal vestibular function in that ear. Patients with known bilateral conductive hearing loss, with known bilateral vestibular disease and those with Tullio phenomenon were not included in the evaluation. It was found that there was an age-related decrease in VEMP amplitude and an increase in VEMP latency that appeared to be rather constant throughout the whole age span. The VEMP data were also compared to an additional group of 10 patients with Tullio phenomenon. Although these 10 patients did have rather large VEMP, equally large VEMP amplitudes were observed in a proportion of unaffected subjects of a similar age group. Thus, the finding of a large VEMP amplitude in response to a high-intensity sound stimulation is not, per se, distinctive for a significant vestibular hypersensitivity to sounds., (Copyright 2007 S. Karger AG, Basel.)

The vestibular semicircular canals are responsible for detection of rotational head motion although the precise mechanisms underlying the transduction and encoding of movement information are still under study. In the present investigation, we utilized neural tracers and immunohistochemistry to quantitatively examine the topology and afferent innervation patterns of the horizontal semicircular canal crista (HCC) in pigeons (Columba livia). Two hundred and eighty-six afferents from five horizontal canal organs were identified of which 92 units were sufficiently labeled and isolated to perform anatomical reconstructions. In addition, a three-dimensional contour map of the crista was constructed. Bouton afferents were located only in the peripheral regions of the receptor epithelium. Bouton afferents had the most complex innervation patterns with significantly longer and more numerous branches as well as a higher branch order than any other fiber type. Bouton fibers also contained significantly more bouton terminals than did dimorph afferents. Calyx afferents were located only in the apex and central planar regions. Calyx fibers had the largest axonal diameters yet the smallest fiber lengths and innervation areas, the fewest number of branches, the lowest branch order, and the fewest total number of terminals of all fiber types. Dimorph afferents were located throughout the central crista with afferent terminations that were larger and more complex than calyx fibers but less so than bouton fibers. Overall, the pigeon HCC morphology and innervation shares many common features with those of other animal classes.

We sought to determine whether the dynamic visual acuity (DVA) test, which has been used to measure the function of the two horizontal semicircular canals (SCCs), could be adapted to measure the individual function of all six SCCs using transient, rapid, unpredictable head rotation stimuli (head thrusts) in the direction of maximum sensitivity of each SCC. We examined head-thrust DVA (htDVA) performance in 19 healthy control subjects, five patients before and six patients after plugging of one superior SCC for treatment of superior canal dehiscence, and two subjects with unilateral vestibular deafferentation (UVD) by vestibular neurectomy. We compared htDVA results for each SCC to vestibulo-ocular reflex gains measured using 3-D scleral coil recordings during a passive head-thrust-test paradigm. Individuals with normal vestibular function had similar htDVA scores for each of the six directions (canals) tested (mean 0.058 +/- 0.050 LogMAR). Individuals tested after surgical plugging of one superior SCC were similar to normal for all SCCs except the plugged SCC, which had significantly worse htDVA scores (mean 0.270 +/- 0.08 LogMAR). Individuals with UVD had significantly worse htDVA scores for head rotations maximally exciting any of the ipsilesional SCC (mean 0.317 +/- 0.129 LogMAR) and scores similar to normal subjects for contralesional rotations (0.063 +/- 0.051 LogMAR). These findings suggest that the htDVA test, which does not require scleral coil placement, magnetic field coils, or expensive oculography equipment, can provide a useful quantitative measure of individual SCC function.

A neural network model was developed to explain the gravity-dependent properties of gain adaptation of the angular vestibuloocular reflex (aVOR). Gain changes are maximal at the head orientation where the gain is adapted and decrease as the head is tilted away from that position and can be described by the sum of gravity-independent and gravity-dependent components. The adaptation process was modeled by modifying the weights and bias values of a three-dimensional physiologically based neural network of canal-otolith-convergent neurons that drive the aVOR. Model parameters were trained using experimental vertical aVOR gain values. The learning rule aimed to reduce the error between eye velocities obtained from experimental gain values and model output in the position of adaptation. Although the model was trained only at specific head positions, the model predicted the experimental data at all head positions in three dimensions. Altering the relative learning rates of the weights and bias improved the model-data fits. Model predictions in three dimensions compared favorably with those of a double-sinusoid function, which is a fit that minimized the mean square error at every head position and served as the standard by which we compared the model predictions. The model supports the hypothesis that gravity-dependent adaptation of the aVOR is realized in three dimensions by a direct otolith input to canal-otolith neurons, whose canal sensitivities are adapted by the visual-vestibular mismatch. The adaptation is tuned by how the weights from otolith input to the canal-otolith-convergent neurons are adapted for a given head orientation.

Studies have reported a functional link between the arc size of the semicircular canals and locomotor agility across adult primates. However, canal size is spatially interlinked with the subarcuate fossa. This fossa can house the petrosal lobule of the paraflocculus, which also plays a role in coordinating head and eye movements. Consequently, it could be that it is the size of the petrosal lobule and fossa that are directly associated with locomotor agility, and not canal arc size. The apparent association of the latter would only follow from the spatial requirement of the canals to accommodate a suitably enlarged subarcuate fossa and petrosal lobule. This study aims to test the ontogenetic basis of this argument by examining high-resolution magnetic resonance images of fetal samples of Homo sapiens, Macaca nemestrina, and Alouatta caraya. Falsifiable null hypotheses examined are (1) that development of the subarcuate fossa is initiated by growth of the petrosal lobule, and (2) that growth of the semicircular canals and of the subarcuate fossa are independent. The findings confirm that the subarcuate fossa forms independently of a petrosal lobule in all three species, thereby falsifying the first hypothesis. Significant correlations were observed between size variables of the semicircular canals and the subarcuate fossa, particularly between the anterior canal and the opening of the fossa. These results falsify the hypothesis that the canals and fossa grow entirely independently. In the human sample, canal growth outpaces fossa growth, possibly because no petrosal lobule is present in humans. In the other two species, the subarcuate fossa simply seems to fill the space made available by canal growth. However, fossa enlargement cannot be excluded as an influence on size increase in the canals. Nevertheless, taken together, the results suggest that canal size is unlikely to be determined primarily by the spatial requirements of the subarcuate fossa and petrosal lobule, rather than by sensory demands reflected in the empirically established link with locomotor agility.

The main objective of this study was to determine whether bone-conducted vibration (BCV) is equally effective in activating both semicircular canal and otolith afferents in the guinea pig or whether there is preferential activation of one of these classes of vestibular afferents. To answer this question a large number (346) of single primary vestibular neurons were recorded extracellularly in anesthetized guinea pigs and were identified by their location in the vestibular nerve and classed as regular or irregular on the basis of the variability of their spontaneous discharge. If a neuron responded to angular acceleration it was classed as a semicircular canal neuron, if it responded to maintained roll or pitch tilts it was classified as an otolith neuron. Each neuron was then tested by BCV stimuli-either clicks, continuous pure tones (200-1,500 Hz) or short tone bursts (500 Hz lasting 7 ms)-delivered by a B-71 clinical bone-conduction oscillator cemented to the guinea pig's skull. All stimulus intensities were referred to that animal's own auditory brainstem response (ABR) threshold to BCV clicks, and the maximum intensity used was within the animal's physiological range and was usually around 70 dB above BCV threshold. In addition two sensitive single axis linear accelerometers cemented to the skull gave absolute values of the stimulus acceleration in the rostro-caudal direction. The criterion for a neuron being classed as activated was an audible, stimulus-locked increase in firing rate (a 10% change was easily detectable) in response to the BCV stimulus. At the stimulus levels used in this study, semicircular canal neurons, both regular and irregular, were insensitive to BCV stimuli and very few responded: only nine of 189 semicircular canal neurons tested (4.7%) showed a detectable increase in firing in response to BCV stimuli up to the maximum 2 V peak-to-peak level we delivered to the B-71 oscillator (which produced a peak-to-peak skull acceleration of around 6-8 g and was usually around 60-70 dB above the animal's own ABR threshold for BCV clicks). Regular otolithic afferents likewise had a poor response; only 14 of 99 tested (14.1%) showed any increase in firing rate up to the maximum BCV stimulus level. However, most irregular otolithic afferents (82.8%) showed a clear increase in firing rate in response to BCV stimuli: of the 58 irregular otolith neurons tested, 48 were activated, with some being activated at very low intensities (only about 10 dB above the animal's ABR threshold to BCV clicks). Most of the activated otolith afferents were in the superior division of the vestibular nerve and were probably utricular afferents. That was confirmed by evidence using juxtacellular injection of neurobiotin near BCV activated neurons to trace their site of origin to the utricular macula. We conclude there is a very clear preference for irregular otolith afferents to be activated selectively by BCV stimuli at low stimulus levels and that BCV stimuli activate some utricular irregular afferent neurons. The BCV generates compressional and shear waves, which travel through the skull and constitute head accelerations, which are sufficient to stimulate the most sensitive otolithic receptor cells.

Using collision tests of orthodromically and antidromically generated spikes, we studied the axonal pathways, axonal projection levels, and soma location of anterior semicircular canal (AC) nerve-activated vestibulospinal neurons in decerebrate cats. AC nerve-activated vestibulospinal neurons (n=74) were mainly located in the ventral portion of the lateral vestibular nuclei and the rostral portion of the descending vestibular nucleus, which is consistent with previous studies. Of these neurons, 15% projected through the ipsilateral (i-) lateral vestibulospinal tract (LVST), 74% projected through the medial vestibulospinal tract (MVST), and 11% projected through the contralateral (c-) LVST. The vast majority (78%) of AC nerve-activated vestibulospinal neurons were activated antidromically only from the cervical segment of the spinal cord; 15% of neurons were activated from the T1 segment and only one neuron was activated from the L3 segment. AC nerve-activated vestibulospinal neurons may primarily target the neck muscles and thus contribute to the vestibulocollic reflex. Most of the c-LVST neurons were also activated antidromically from the oculomotor nucleus, suggesting that they are closely related to the control of combined eye-head movements.

Perception of tilt (somatogravic illusion) in response to sustained linear acceleration is generally attributed to the otolithic system which reflects either a translation of the head or a reorientation of the head with respect to gravity (tilt/translation ambiguity). The main aim of this study was to compare the tilt perception during prolonged static tilt and translation between 8 and 20 degrees of tilt relative to the gravitoinertial forces (i.e., G and GIF, respectively) when the semicircular cues were no more available. An indirect measure of tilt perception was estimated by means of a visual and kinesthetic judgment of the gravitational horizon. The main results contrast with the interpretation regarding the tilt/translation ambiguity as the same orientation relative to the shear forces G for the true tilt or GIF in the centrifuge did not induce the same horizon perception. Visual adjustment and arm pointing in the centrifuge were always above the ones observed in a G environment. Part of the lowering of the judgment in the centrifuge may be related to the mechanical effect of GIF on the effectors as shown by the shift of the egocentric coordinates in the direction of GIF. The role of the extravestibular graviceptors in the judgment of the degree of tilt of one's own body relative to G or GIF was discussed.

Alignment of the body to the gravitational vertical is considered to be the key to human bipedalism. However, changes to the semicircular canals during human evolution suggest that the sense of head rotation that they provide is important for modern human bipedal locomotion. When walking, the canals signal a mix of head rotations associated with path turns, balance perturbations, and other body movements. It is uncertain how the brain uses this information. Here, we show dual roles for the semicircular canals in balance control and navigation control. We electrically evoke a head-fixed virtual rotation signal from semicircular canal nerves as subjects walk in the dark with their head held in different orientations. Depending on head orientation, we can either steer walking by "remote control" or produce balance disturbances. This shows that the brain resolves the canal signal according to head posture into Earth-referenced orthogonal components and uses rotations in vertical planes to control balance and rotations in the horizontal plane to navigate. Because the semicircular canals are concerned with movement rather than detecting vertical alignment, this result shows the importance of movement control and agility rather than precise vertical alignment of the body for human bipedalism.

Cathodal galvanic currents activate primary vestibular afferents, whereas anodal currents inhibit them. Pulsed galvanic vestibular stimulation (GVS) was used to determine the latency and initiation of the human vestibuloocular reflex. Three-dimensional galvanic vestibuloocular reflex (g-VOR) was recorded with binocular dual-search coils in response to a bilateral bipolar 100-ms rectangular pulse of current at 0.9 (near-threshold), 2.5, 5.0, 7.5, and 10.0 mA in 11 normal subjects. The g-VOR consisted of three components: conjugate torsional eye rotation away from cathode toward anode; vertical divergence (skew deviation) with hypertropia of the eye on the cathodal and hypotropia of the eye on the anodal sides; and conjugate horizontal eye rotation away from cathode toward anode. The g-VOR was repeatable across all subjects, its magnitude a linear function of the current intensity, its latency about 9.0 ms with GVS of >or=2.5 mA, and was not suppressed by visual fixation. At 10-mA stimulation, the g-VOR [x, y, z] on the cathodal side was [0.77 +/- 0.10, -0.05 +/- 0.05, -0.18 +/- 0.06 degrees ] (mean +/- 95% confidence intervals) and on the anodal side was [0.79 +/- 0.10, 0.16 +/- 0.05, -0.19 +/- 0.06 degrees ], with a vertical divergence of 0.20 degrees . Although the horizontal g-VOR could have arisen from activation of the horizontal semicircular canal afferents, the vertical-torsional g-VOR resembled the vestibuloocular reflex in response to roll-plane head rotation about an Earth-horizontal axis and might be a result of both vertical semicircular canal and otolith afferent activations. Pulsed GVS is a promising technique to investigate latency and initiation of the human vestibuloocular reflex because it does not require a large mechanical apparatus nor does it pose problems of head inertia or slippage.

Few data are available concerning single Ca channel properties in inner ear hair cells and particularly none in vestibular type I hair cells. By using the cell-attached configuration of the patch-clamp technique in combination with the semicircular canal crista slice preparation, we determined the elementary properties of voltage-dependent Ca channels in chicken embryo type I and type II hair cells. The pipette solutions included Bay K 8644. With 70 mM Ba(2+) in the patch pipette, Ca channel activity appeared as very brief openings at -60 mV. Ca channel properties were found to be similar in type I and type II hair cells; therefore data were pooled. The mean inward current amplitude was -1.3 +/- 0.1 (SD) pA at - 30 mV (n = 16). The average slope conductance was 21 pS (n = 20). With 5 mM Ba(2+) in the patch pipette, very brief openings were already detectable at -80 mV. The mean inward current amplitude was -0.7 +/- 0.2 pA at -40 mV (n = 9). The average slope conductance was 11 pS (n = 9). The mean open time and the open probability increased significantly with depolarization. Ca channel activity was still present and unaffected when omega-agatoxin IVA (2 microM) and omega-conotoxin GVIA (3.2 microM) were added to the pipette solution. Our results show that types I and II hair cells express L-type Ca channels with similar properties. Moreover, they suggest that in vivo Ca(2+) influx might occur at membrane voltages more negative than -60 mV.

Background: Spatial disorientation is an important problem in aviation. The significance of the C level for illusions elicited from the semicircular canals is not clear. The aim of the present investigation was to elucidate how a gravitoinertial force, acting in parallel with the subject's long (z) axis, may influence the magnitude and persistence of canal-induced tilts of the subjective visual horizontal (SVH) present after acceleration in a gondola centrifuge., Methods: The SVH was measured by means of an adjustable luminous line in darkness. Two series of experiments were performed. In series 1, the SVH was measured in 13 subjects at 1.1 G, 1.7 G, and 2.5 G. In series 2, it was measured in 8 subjects at 2.5 G and 4.5 G., Results: After acceleration of the centrifuge the SVH was tilted relative to the gravitoinertial horizontal. The direction of tilt was compensatory to the gondola inclination. In series 1 the initial SVH tilt was: 16.2 +/- 7.0 degrees (1.1 G), 24.2 +/- 10.2 degrees (1.7 G), and 27.1 +/- 13.9 degrees (2.5 G). In series 2 it was: 27.6 +/- 14.6 degrees (2.5 G), and 31.2 +/- 18.8 degrees (4.5 G). The gain for this response, defined as the ratio between the initial tilt and the inclination of the gondola, was: 0.65 +/- 0.28 (1.1 G), 0.45 +/- 0.19(1.7 G), 0.41 +/- 0.21 (2.5 G) (series 1); and 0.42 +/- 0.22 (2.5 G), and 0.40 +/- 0.24 (4.5 G) (series 2). Thus, an increase from 1.1 G to 1.7 G caused a reduction in the gain, but at G levels beyond 1.7 G there was no further decrease. The time constant for exponential decay tended to increase with the G level. It was: 61 +/- 31 s (1.1 G), 84 +/- 36 s (1.7 G), 89 +/- 42 s (2.5 G) (series 1); and 67 +/- 49 s (2.5 G), and 101 +/- 73 s (4.5 G) (series 2)., Conclusion: It appears that otolithic stimulation via an increased gravitoinertial force vector, acting in parallel with the head and body long axis, does not substantially influence the magnitude of the canal-mediated sensation of roll-tilt after acceleration in a swing-out gondola centrifuge. Nor does it reduce the duration of this sensation.

Multiunit activity during horizontal sinusoidal motion was recorded from pairs of oculomotor, trochlear, or abducens nerves of an in vitro turtle brainstem preparation that received inputs from intact semicircular canals. Responses of left oculomotor, right trochlear and right abducens nerves were approximately aligned with leftward head velocity, and that of the respective contralateral nerves were in-phase with rightward velocity. We examined the effect of sectioning or injecting lidocaine (1-2 microL of 0.5%) into the right vestibular nerve. Nerve block caused a striking phase shift in the evoked response of right oculomotor and left trochlear nerves, in which (rightward) control responses were replaced by a smaller-amplitude response to leftward table motion. Such "phase-reversed" responses were poorly defined in abducens nerve recordings. Frequency analysis demonstrated that this activity was advanced in phase relative to post-block responses of the respective contralateral nerves, which were in turn phase-advanced relative to pre-block controls. Phase differences were largest (approximately 10 degrees) at low frequencies (approximately 0.1 Hz) and statistically absent at 1 Hz. The phase-reversed responses were further investigated by eliminating individual canal input from the left labyrinth following right nVIII block, which indicated that the activation of the vertical canal afferents is the source of this activity.

Background: When exposed to an increased gravitoinertial force, a subject, sitting upright, experiences an illusion of being tilted backwards. This so-called "G-excess illusion" is generally ascribed to the otolith organs. The present study aimed at elucidating how stimulation of the semicircular canals may influence the development of the G-excess illusion., Methods: The visually perceived eye level (VPEL) was measured by means of a visual indicator in a large swing-out gondola centrifuge. The roll position of the gondola was controlled so that the subject was always upright with respect to the resultant vector of the Earth gravity force and the centrifugal force. Subjects (n = 8) underwent four centrifuge runs (2 G, 5 min), sitting in different positions, i.e., heading forwards, backwards, centripetally, and centrifugally., Results: At the 2-G plateau there was a depression of the VPEL which was initially small but increased with a time constant of 90 +/- 30 s toward an asymptote of -22.0 +/- 6.9 degrees (mean and 1 SD for all positions). The initial depression was significantly smaller for the centripetal (+2.0 +/- 14.6 degrees) than for the centrifugal position (-14.5 +/- 10.4 degrees). However, there was no difference between the forward (-5.6 +/- 4.8 degrees) and backward (-4.0 +/- 4.5 degrees) positions. Initially after deceleration of the centrifuge to 1 G there was still a significant depression of the VPEL (-13.5 +/- 7.9 degrees), decreasing with a time constant of 100 +/- 46 s., Conclusions: The considerable delay in the otolith-mediated changes in the VPEL is interpreted as due to the absence of adequate canal information for a change in head position. The difference in VPEL between the centripetal and centrifugal positions suggests an influence of canal change-in-position information. However, pitch-plane angular velocity, being of considerable magnitude but of opposite sign for the forward and backward positions, did not influence the VPEL.

The orientations of the semicircular canals determines the response of the canals to head rotations and, in turn, the brain's ability to interpret those motions. The geometry of chinchillas' semicircular canals has never been reported. Volumetric representations of three chinchilla skulls were generated using a microCT scanner. The centroids of each semicircular canal lumen were identified as they passed through the image slices and were regressed to a plane. Unit vectors normal to the plane representing canal orientations were used to calculate angles between canal pairs. Pitch and roll maneuvers required to bring any canal into the horizontal plane for physiologic investigation were calculated. The semicircular canals of the chinchilla were found to be relatively planar. The horizontal canal was found to be oriented 55.0 degrees anteriorly upward. Pairs of ipsilateral chinchilla canals were not orthogonal and contralateral synergistic pairs were not parallel. Despite this arrangement, the canal plane unit normal vectors were organized to respond with approximately equal overall sensitivity to rotations in any direction. The non-orthogonal chinchilla labyrinth may provide an opportunity to determine whether the frame of reference used by the central vestibular and oculomotor system is based on directions of afferent maximum sensitivity or prime directions.

Human spatial orientation relies on vision, somatosensory cues, and signals from the semicircular canals and the otoliths. The canals measure rotation, whereas the otoliths are linear accelerometers, sensitive to tilt and translation. To disambiguate the otolith signal, two main hypotheses have been proposed: frequency segregation and canal-otolith interaction. So far these models were based mainly on oculomotor behavior. In this study we investigated their applicability to human self-motion perception. Six subjects were rotated in yaw about an off-vertical axis (OVAR) at various speeds and tilt angles, in darkness. During the rotation, subjects indicated at regular intervals whether a briefly presented dot moved faster or slower than their perceived self-motion. Based on such responses, we determined the time course of the self-motion percept and characterized its steady state by a psychometric function. The psychophysical results were consistent with anecdotal reports. All subjects initially sensed rotation, but then gradually developed a percept of being translated along a cone. The rotation percept could be described by a decaying exponential with a time constant of about 20 s. Translation percept magnitude typically followed a delayed increasing exponential with delays up to 50 s and a time constant of about 15 s. The asymptotic magnitude of perceived translation increased with rotation speed and tilt angle, but never exceeded 14 cm/s. These results were most consistent with predictions of the canal-otolith-interaction model, but required parameter values that differed from the original proposal. We conclude that canal-otolith interaction is an important governing principle for self-motion perception that can be deployed flexibly, dependent on stimulus conditions.

Using vestibular sensors to maintain visual stability during changes in head tilt, crucial when panoramic cues are not available, presents a computational challenge. Reliance on the otoliths requires a neural strategy for resolving their tilt/translation ambiguity, such as canal-otolith interaction or frequency segregation. The canal signal is subject to bandwidth limitations. In this study, we assessed the relative contribution of canal and otolith signals and investigated how they might be processed and combined. The experimental approach was to explore conditions with and without otolith contributions in a frequency range with various degrees of canal activation. We tested the perceptual stability of visual line orientation in six human subjects during passive sinusoidal roll tilt in the dark at frequencies from 0.05 to 0.4 Hz (30 degrees peak to peak). Because subjects were constantly monitoring spatial motion of a visual line in the frontal plane, the paradigm required moment-to-moment updating for ongoing ego motion. Their task was to judge the total spatial sway of the line when it rotated sinusoidally at various amplitudes. From the responses we determined how the line had to be rotated to be perceived as stable in space. Tests were taken both with (subject upright) and without (subject supine) gravity cues. Analysis of these data showed that the compensation for body rotation in the computation of line orientation in space, although always incomplete, depended on vestibular rotation frequency and on the availability of gravity cues. In the supine condition, the compensation for ego motion showed a steep increase with frequency, compatible with an integrated canal signal. The improvement of performance in the upright condition, afforded by graviceptive cues from the otoliths, showed low-pass characteristics. Simulations showed that a linear combination of an integrated canal signal and a gravity-based signal can account for these results.

Previous studies of vestibulo-ocular function in patients with anxiety disorders have suggested a higher prevalence of peripheral vestibular dysfunction compared to control populations, especially in panic disorder with agoraphobia. Also, our recent companion studies have indicated abnormalities in postural control in patients with anxiety disorders who report a high degree of space and motion discomfort. The aim of the present study was to assess the VOR, including the semicircular canal-ocular reflex, the otolith-ocular reflex, and semicircular canal-otolith interaction, in a well-defined group of patients with anxiety disorders. The study included 72 patients with anxiety disorders (age 30.6 +/- 10.6 yrs; 60 (83.3% F) and 29 psychiatrically normal controls (age 35.0 +/minus; 11.6 yrs; 24 (82.8% F). 25 patients had panic disorder; 47 patients had non-panic anxiety. Patients were further categorized based on the presence (45 of 72) or absence (27 of 72) of height phobia and the presence (27 of 72) or absence (45 of 72) of excessive space and motion discomfort (SMD). Sinusoidal and constant velocity earth-vertical axis rotation (EVAR) was used to assess the semicircular canal-ocular reflex. Constant velocity off-vertical axis rotation (OVAR) was used to assess both the otolith-ocular reflex and static semicircular canal-otolith interaction. Sinusoidal OVAR was used to assess dynamic semicircular canal-otolith interaction. The eye movement response to rotation was measured using bitemporal electro-oculography. Results showed a significantly higher VOR gain and a significantly shorter VOR time constant in anxiety patients. The effect of anxiety on VOR gain was significantly greater in patients without SMD as compared to those with SMD. Anxiety patients without height phobia had a larger OVAR modulation. We postulate that in patients with anxiety, there is increased vestibular sensitivity and impaired velocity storage. Excessive SMD and height phobia seem to have a mitigating effect on abnormal vestibular sensitivity, possibly via a down-weighting of central vestibular pathways.

This paper presents a biomechanical model of the semicircular canals of the human vestibular system and the design of a 3D biomimetic structure that mimics the biological system. Starting from anatomical and physiological data, mechanical and structural parameters have been identified and a mathematical model has been formulated, by considering the semicircular organ as a canal filled by a liquid. The mathematical and mechanical models were used to simulate the behavior of the semicircular canals under known conditions of angular velocity and acceleration along three axes. Furthermore, the membrane inside the semicircular canals was simulated to understand what the mechanical properties of the membrane are and if polymeric materials can reproduce the mechanical characteristics of the biological organ. The results obtained from the model allow to design a biomimetic organ, as a part of a biomimetic vestibular system, by following this biomechatronic approach.

The subjective visual horizontal (SVH) was measured in the upright position and at 10, 20, and 30 degrees of head and body tilt to the right and left. Normal subjects (n=25) were tested on two separate occasions with an interval of 1-14 days. Test variables considered were the SVH in the upright position, the perception of tilt to the right and left, calculated on the basis of the SVH in the upright and tilted positions, and the asymmetry in tilt perception. There was no correlation between the perception of tilt to the right and to the left r=0.10). Neither was there any correlation between the SVH in the upright position, representing a resting asymmetry, and the asymmetry in tilt perception, i.e. the response asymmetry (r=0.17). However, for each variable, there was a high correspondence between data obtained at test and retest (r ranged from 0.68 to 0.89, p<0.001), suggesting that the independence between variables is not due to noise. Findings are discussed taking into consideration the possible roles of otoliths and semicircular canals in the formation of the SVH. In an attempt to explain the independence between the two measures of asymmetry it is hypothesized that while the otoliths must be essential for the perception of static lateral tilt, the SVH in the upright position to a considerable degree reflects semicircular canal function.

Vestibulo-ocular and second-order neurons in medial and superior vestibular nuclei of alert cats were identified by antidromic and orthodromic electrical stimulation, and their responses to whole body rotations were recorded in the dark. Neurons that had spatial sensitivity most closely aligned with the anterior canal (anterior canal neurons) were compared with neurons that had spatial sensitivity most closely aligned with the posterior canal (posterior canal neurons). Responses were recorded during low frequency earth-horizontal axis pitch rotations in the normal upright posture, and during earth-vertical axis pitch with the head and body lying on the left side. During upright pitch, response phases of anterior canal neurons slightly lagged those of posterior canal neurons or primary vestibular afferents, as previously reported. During on-side pitch, anterior canal neurons showed far greater phase leads with respect to head velocity than posterior canal neurons, primary vestibular afferents, or previously reported vestibulo-ocular reflex eye movements. These results provide challenges for vestibulo-ocular reflex models to incorporate central mechanisms for phase leads among the inputs to anterior canal neurons and to explain how the anterior canal neuron signals reported here combine with other signals to produce observed vestibulo-ocular reflex behavior.

Three subnuclei within the inferior olive are implicated in the control of eye movement; the dorsal cap (DC), the beta-nucleus and the dorsomedial cell column (DMCC). Each of these subnuclei can be further divided into clusters of cells that encode specific parameters of optokinetic and vestibular stimulation. DC neurons respond to optokinetic stimulation in one of three planes, corresponding to the anatomical planes of the semicircular canals. Neurons in the beta-nucleus and DMCC respond to vestibular stimulation in the planes of the vertical semicircular canals and otoliths. Each these olivary nuclei receives excitatory and inhibitory signals from pre-olivary structures. The DC receives excitatory signals from the ipsilateral nucleus of the optic tract (NOT) and inhibitory signals from the contralateral nucleus prepositus hypoglossi (NPH). The beta-nucleus and DMCC receive inhibitory signals from the ipsilateral nucleus parasolitarius (Psol) and excitatory signals from the contralateral dorsal Y group. Consequently, the olivary projection to the cerebellum, although totally crossed, still represents bilateral sensory stimulation. Inputs to the inferior olive from the NOT, NPH, Psol or Y-group discharge at frequencies of 10-100 imp/s. CFRs discharge at 1-5 imp/s; a frequency reduction of an order of magnitude. Inferior olivary projections to the contralateral cerebellum are sagittally arrayed onto multiple cerebellar folia. These arrays establish coordinate systems in the flocculus and nodulus, representing head-body movement. These climbing fiber-defined spatial coordinate systems align Purkinje cell discharge onto subjacent cerebellar and vestibular nuclei. In the oculomotor system, olivo-cerebellar circuitry enhances and modifies eye movements based on movement of the head-body in space.

Although the effectiveness of histamine-related drugs in the treatment of peripheral and central vestibular disorders may be explained by their action on the vestibular nuclei, it has also been shown that antivertigo effects can take place at the peripheral level. In this work, we examined the actions of H3 histaminergic agonists and antagonists on the afferent neuron electrical discharge in the isolated inner ear of the axolotl. Our results indicate that H3 antagonists such as thioperamide, clobenpropit, and betahistine (BH) decreased the electrical discharge of afferent neurons by interfering with the postsynaptic response to excitatory amino acid agonists. These results lend further support to the idea that the antivertigo action of histamine-related drugs may be caused, at least in part, by a decrease in the sensory input from the vestibular endorgans. The present data show that the inhibitory action of the afferent neurons discharge previously described for BH is not restricted to this molecule but is also shared by other H3 antagonists.

Type I and Type II hair cells, and Type II hair cells located in different zones of the semicircular canal crista, express different patterns of voltage-dependent K channels, each one specifically shaping the hair cell receptor potential. We report here that, close to hatching, chicken embryo semicircular canal Type I and Type II hair cells express a similar voltage-dependent L-type calcium current (I(Ca)), whose main features are: activation above -60 mV, fast activation kinetics, and scarce inactivation. I(Ca) should be already active at rest in Zone 1 Type II hair cells, whose resting membrane potential was on average slightly less negative than -60 mV. Conversely, I(Ca) would not be active at rest in Type II hair cells from Zone 2 and 3, nor in Type I hair cells, since their resting membrane potential was significantly more negative than -60 mV. However, even small depolarising currents would activate I(Ca) steadily in Zone 2 and 3 Type II hair cells, but not in Type I hair cells because of the robust repolarising action of their specific array of K(+) currents. The implications of the present findings in the afferent discharge are discussed.

Regional estimates of type I and type II vestibular hair cells (HC) and supporting cell (SC) numbers were obtained from the horizontal crista ampullaris by using design-based stereology in human. Cristae were microdissected from temporal bones obtained post-mortem (N=16, age range 26-98 years). Three groups were made according to age: group 1, n=5, ages between 26 and 67 years, average age 51 years; group 2, n=4, average age 84 years; and group 3, n=7, average age 94 years. For group 1, the average total HC number was 8,005+/-214, corresponding to 4,119+/-107 type I HC, 3,886+/-117 type II HC, and 10,274+/-224 SC. The type I:type II HC ratio was 1.06+/-0.01, and HC density was 0.80 cells/100 microm2. For group 2, the average total HC number was 7,074+/-489, corresponding to 3,733+/-212 type I HC, 3,341+/-314 type II HC, and 9,321+/-858 SC. The type I:II HC ratio was 1.12+/-0.06, and HC density was 0.75 cells/100 microm2. For group 3, the average HC number was 6,009+/-327, corresponding to 3,380+/-223 type I HC, 2,628+/-235 type II HC, and 10,185+/-182 SC. The type I:II HC ratio was 1.34+/-0.10, and HC density was 0.63 cells/100 microm2. A significant decline in type I, type II, and total HC number and density was found in groups 2 and 3, with individuals exceeding the average human life span., (Copyright (c) 2005 Wiley-Liss, Inc.)

During locomotion, retinal flow, gaze angle, and vestibular information can contribute to one's perception of self-motion. Their respective roles were investigated during active steering: Retinal flow and gaze angle were biased by altering the visual information during computer-simulated locomotion, and vestibular information was controlled through use of a motorized chair that rotated the participant around his or her vertical axis. Chair rotation was made appropriate for the steering response of the participant or made inappropriate by rotating a proportion of the veridical amount. Large steering errors resulted from selective manipulation of retinal flow and gaze angle, and the pattern of errors provided strong evidence for an additive model of combination. Vestibular information had little or no effect on steering performance, suggesting that vestibular signals are not integrated with visual information for the control of steering at these speeds., (((c) 2005 APA, all rights reserved).)

Background: Spatial disorientation is an important problem in aviation. The mechanisms behind the sensation of roll tilt during coordinated turns are not well known. The present study aimed at elucidating what kind of semicircular canal information might cause tilts of the subjective horizontal during gondola centrifugation., Methods: The subjective visual horizontal (SVH) was measured by means of an adjustable visual line in darkness. Subjects (n = 8) underwent four centrifuge runs (2 G, 5 min), sitting in different positions, i.e., heading forwards, backwards, centripetally, and centrifugally. The roll position of the gondola (60 degrees at 2 G) was controlled so that the subject was always upright with respect to the resultant gravitoinertial force vector. Thus, the semicircular-canal stimulus components in yaw, pitch, and roll were varied to some extent independently of each other., Results: For the forward position the SVH was substantially tilted in a direction compensatory with respect to the inclination of the gondola. For the backward position there was also a tendency to a compensatory SVH tilt. In all subjects the magnitude of tilt was larger for the forward position than for the backward. The group means were +20.9 +/- 8.4 degrees and -6.9 +/- 10.5 degrees (positive sign designates a clockwise deviation of the SVH), p < 0.001, n = 8. There were no significant SVH tilts for the centripetal (+6.4 +/- 10.7 degrees) and centrifugal (+2.1 +/- 4.8 degrees) positions. The effects of deceleration of the centrifuge were very small for all positions., Conclusion: These findings suggest that the substantial SVH tilt after acceleration heading forwards is not directly related to any single component of semicircular canal stimulation but depends on the ability of the brain to expediently process complex stimulus patterns.

The visually perceived eye level (VPEL) was measured during gondola centrifugation. Subjects (N = 11) were seated upright, facing motion in a swing-out gondola The head was adjusted so that Reid's baseline was tilted 10 degrees anterior end up. The subjects were requested to adjust the position of a small luminous dot so that it was perceived as gravitationally at eye level. In the 1-g environment, the VPEL was a few degrees below the true gravitational eye level (M = -1.75 degrees, SD = 1.90 degrees). After rapid acceleration of the centrifuge to 2 G (vectorial sum of the earth gravity force and the centrifugal force), there was an exponentially increasing depression of the VPEL. The initial value was -6.4 degrees +/- 5.2 degrees. During 10 min at 2 G, the VPEL approached an asymptotic value of -24.8 degrees +/- 5.4 degrees. The time constant showed a large interindividual variability, ranging from 59 to 1,000 sec (M = 261 sec, median = 147 sec). The findings are discussed, taking into consideration otolith-semicircular-canal interaction, as well as memory functions of the vestibular system.

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.

Analysis of vestibulo-ocular reflex experiments requires knowledge of the absolute orientations (with respect to skull landmarks) of semicircular canals (SCC). Data relating SCC orientations to accessible skull landmarks in humans are sparse, apart from a classic study of 10 skulls, which concluded that the horizontal and anterior SCC are not mutually orthogonal (111 +/- 7.6 degrees). Multiple studies of isolated labyrinths have shown the inter-SCC angles are close to 90 degrees. We hypothesized that a larger sample would yield mean absolute SCC orientations closer to the mutual orthogonality demonstrated for isolated labyrinths. We measured canal orientations with respect to accessible skull landmarks using 3-D multiplanar reconstructions of computerized tomography scans of the temporal bones of 22 human subjects. Images were acquired with 0.5-mm thickness and reconstructed with in-plane resolution of 234 microm. There was no significant difference between the left and a mirror image of the right (p > 0.57 on multiway ANOVA of orientation vector coefficients), so data were pooled for the 44 labyrinths. The angle between the anterior and posterior SCC was 94.0 +/- 4.0 degrees (mean +/- SD). The angle between the anterior and horizontal SCC was 90.6 +/- 6.2 degrees. The angle between the horizontal and posterior SCC was 90.4 +/- 4.9 degrees. The direction angles between a vector normal to the left horizontal SCC and the positive Reid's stereotaxic X (+nasal), Y (+left), and Z (+superior) axes were 108.7 +/- 7.5 degrees, 92.2 +/- 5.7 degrees, and 19.9 +/- 7.0 degrees, respectively. The angles between a vector normal to the left anterior SCC and the positive Reid's stereotaxic X, Y, and Z axes were 125.9 +/- 5.2 degrees, 38.4 +/- 5.1 degrees, and 100.1 +/- 6.2 degrees, respectively. The angles between a vector normal to the left posterior SCC and the positive Reid's stereotaxic X, Y, and Z axes were 133.6 +/- 5.3 degrees, 131.5 +/- 5.1 degrees, and 105.6 +/- 6.6 degrees, respectively. The mean anterior SCC-contralateral posterior SCC angle was 15.3 +/- 7.2 degrees. The absolute orientations of human SCC are more nearly orthogonal than previously reported.

The avian lumbosacral vertebral column and spinal cord show a number of specializations which have recently been interpreted as a sense organ of equilibrium. This sense organ is thought to support balanced walking on the ground. Although most of the peculiar structures have been described previously, there was a need to reevaluate the specializations with regard to the possible function as a sense organ. Specializations were studied in detail in the adult pigeon. The development of the system was studied both in the pigeon (semiprecocial at hatching) and in the chicken (precocial). Specializations in the vertebral canal consist of a considerable enlargement, which is not due to an increase in the size of the spinal nervous tissue, but to a large glycogen body embedded in a dorsal rhomboid sinus. The dorsal wall of the vertebral canal shows segmented bilateral dorsal grooves, which are covered by the meninges towards the lumen of the vertebral canal leaving openings in the midline and laterally. This results in a system of lumbosacral canals which look and may function similar to the semicircular canals in the inner ear. Laterally these canals open above ventrolateral protrusions or accessory lobes of the spinal cord which contain neurons. There are large subarachnoidal cerebrospinal fluid spaces, lateral and ventral to the accessory lobes. Movement of this fluid is thought to stimulate the lobes mechanically. As to the development of avian lumbosacral specializations, main attention was given to the organization of the lobes and the adjacent fluid spaces including the dorsal canals. In the pigeon the system is far from being adult-like at hatching but maturates rapidly after hatching. In the chicken the system looks already adult-like at hatching. The implications derived from the structural findings are discussed with regard to a possible function of the lumbosacral specializations as a sense organ of equilibrium. The adult-like organization in the newly hatched chickens, which walk around immediately after hatching, supports the assumed function as a sense organ involved in the control of locomotion on the ground.

In this review, based primarily on work from our laboratory, but related to previous studies, we summarize what is known about the convergence of vestibular afferent inputs onto single vestibular neurons activated by selective stimulation of individual vestibular nerve branches. Horizontal semicircular canal (HC), anterior semicircular canal (AC), posterior semicircular canal (PC), utricular (UT), and saccular (SAC) nerves were selectively stimulated in decerebrate cats. All recorded neurons were classified as either projection neurons, which consisted of vestibulospinal (VS), vestibulo-oculospinal (VOS), vestibulo-ocular (VO) neurons, or non-projection neurons, which we simply term "vestibular'' (V) neurons. The first three types could be successfully activated antidromically from oculomotor/trochlear nuclei and/or spinal cord, and the last type could not be activated antidromically from either site. A total of 1228 neurons were activated by stimulation of various nerve pair combinations. Convergent neurons were located in the caudoventral part of the lateral, the rostral part of the descending, and the medial vestibular nuclei. Otolith-activated vestibular neurons in the superior vestibular nucleus were extremely rare. A high percentage of neurons received excitatory inputs from two nerve pairs, a small percentage received reciprocal convergent inputs and even fewer received inhibitory inputs from both nerves. More than 30% of vestibular neurons received convergent inputs from vertical semicircular canal/otolith nerve pairs. In contrast, only half as many received convergent inputs from HC/otolith-nerve pairs, implying that convergent input from vertical semicircular canal and otolith-nerve pairs may play a more important role than that played by inputs from horizontal semicircular canal and otolith-nerve pairs. Convergent VS neurons projected through the ipsilateral lateral vestibulospinal tract (i-LVST) and the medial vestibulospinal tract (MVST). Almost all the VOS neurons projected through the MVST. Convergent neurons projecting to the oculomotor/trochlear nuclei were much fewer in number than those projecting to the spinal cord. Some of the convergent neurons that receive both canal and otolith input may contribute to the short-latency pathway of the vestibulocollic reflex. The functional significance of these convergences is discussed.

Immediate early gene expression in the cerebellar vermis of cats and squirrel monkeys was stimulated by prolonged whole body rotations. Continuous, earth-horizontal axis rotations that excited only otoliths or high velocity vertical axis rotations that excited only semicircular canals resulted in c-fos immunoreactive nuclei concentrated in the granular layer of lobules X and ventral IX (the nodulus and ventral uvula), which represent the medial parts of the vestibulo-cerebellum. Large clusters of labeled nuclei consisting mainly of granule cells and calretinin-positive unipolar brush cells were present in the granular layer, whereas Purkinje cell nuclei were unlabeled, and labeled basket and stellate cell nuclei were scattered in the molecular layer. In other vermal lobules there was a significant but less dense label than in the nodulus and ventral uvula. Generally, the extent of c-fos labeling of molecular layer interneurons was in relation to nuclear labeling of granular layer neurons: labeling of both basket and stellate cells accompanied nuclear labeling of neurons throughout the depth of the granular layer, whereas only stellate cells were labeled when nuclear labeling was restricted to the superficial granular layer. Yaw horizontal or roll vertical rotations each stimulated c-fos expression in the cat medial vestibulo-cerebellum to approximately the same extent. Low-velocity rotations resulted in much less c-fos expression. Similar, albeit less intense, patterns of c-fos activation were observed in monkeys. Concentrated c-fos expression in the medial vestibulo-cerebellum after exposure to a strong head velocity signal that could originate from either otolith or canal excitation suggests that granule and unipolar brush cells participate in a neuronal network for estimating head velocity, irrespective of the signal source.

Objective: To determine the effects of stimulation of bilateral lateral semicircular canals (LSCCs) by accelerated rotation and caloric stimulation of unilateral LSCC on vestibular evoked myogenic potentials (VEMPs) in healthy volunteers., Methods: In experiment 1, VEMPs were recorded while subjects (n = 11) were seated in a rotational chair and angular acceleration around the earth-vertical axis was provided. Amplitudes of p13-n23 were corrected using background muscle activities. In experiment 2, subjects (n = 8) in the semilateral position kept the LSCC in the vertical position and activated the sternocleidomastoid muscle by twisting the neck. After irrigating the external auditory canal with ice water, VEMPs were recorded on the irrigated side. In experiment 3, the same setting as experiment 2 was applied (n = 6), and hot water of 44 degrees C was used for irrigation., Results: There were no significant differences in latencies of p13 or n23, and in corrected amplitudes by either rotatory or caloric stimulation., Conclusions: Simultaneous stimulation of LSCCs has little effect on VEMPs., Significance: No functional interaction between the saccule and LSCC was detected in VEMPs, although convergence of semicircular canal and otolith nerve inputs onto single vestibular nucleus neurons has been demonstrated electrophysiologically in animal experiments.

Mammalian vestibular-nerve afferents innervating the semicircular canals have been divided into groups according to their discharge regularity, gain at 2-Hz rotational stimulation, and morphology. Low-gain irregular afferents terminate in calyx endings in the central crista, high-gain irregular afferents synapse more peripherally in dimorphic (bouton and calyx) endings, and regular afferents terminate in the peripheral zone as bouton-only and dimorphic endings. The response dynamics of these three groups have been described only up to 4 Hz in previous studies. Reported here are responses of chinchilla semicircular canal vestibular-nerve afferents to rotational stimuli at frequencies up to 16 Hz. The sensitivity of all afferents increased with increasing frequency with the sensitivity of low-gain irregular afferents increasing the most and matching the high-gain irregular afferents at 16 Hz. All afferents increased their phase lead with respect to stimulus velocity at higher frequencies with the highest leads in low-gain irregular afferents and the lowest in regular afferents. No attenuation of sensitivity or shift in phase consistent with the presence of a high-frequency pole over the range tested was noted. Responses were best fit with a torsion-pendulum model combined with a lead operator (tau(HF1)s + 1)(tau(HF2)s + 1). The discharge regularity of individual afferents was correlated to the value of each afferent's lead operator time constants. These findings suggest that low-gain irregular afferents are well suited for encoding the onset of rapid head movements, a property that would be advantageous for initiation of reflexes with short latency such as the vestibulo-ocular reflex.

The vestibular semicircular canals are internal sensors that signal the magnitude, direction, and temporal properties of angular head motion. Fluid mechanics within the 3-canal labyrinth code the direction of movement and integrate angular acceleration stimuli over time. Directional coding is accomplished by decomposition of complex angular accelerations into 3 biomechanical components-one component exciting each of the 3 ampullary organs and associated afferent nerve bundles separately. For low-frequency angular motion stimuli, fluid displacement within each canal is proportional to angular acceleration. At higher frequencies, above the lower corner frequency, real-time integration is accomplished by viscous forces arising from the movement of fluid within the slender lumen of each canal. This results in angular velocity sensitive fluid displacements. Reflecting this, a subset of afferent fibers indeed report angular acceleration to the brain for low frequencies of head movement and report angular velocity for higher frequencies. However, a substantial number of afferent fibers also report angular acceleration, or a signal between acceleration and velocity, even at frequencies where the endolymph displacement is known to follow angular head velocity. These non-velocity-sensitive afferent signals cannot be attributed to canal biomechanics alone. The responses of non-velocity-sensitive cells include a mathematical differentiation (first-order or fractional) imparted by hair-cell and/or afferent complexes. This mathematical differentiation from velocity to acceleration cannot be attributed to hair cell ionic currents, but occurs as a result of the dynamics of synaptic transmission between hair cells and their primary afferent fibers. The evidence for this conclusion is reviewed below.

How do we perceive the visual motion of objects that are accelerated by gravity? We propose that, because vision is poorly sensitive to accelerations, an internal model that calculates the effects of gravity is derived from graviceptive information, is stored in the vestibular cortex, and is activated by visual motion that appears to be coherent with natural gravity. The acceleration of visual targets was manipulated while brain activity was measured using functional magnetic resonance imaging. In agreement with the internal model hypothesis, we found that the vestibular network was selectively engaged when acceleration was consistent with natural gravity. These findings demonstrate that predictive mechanisms of physical laws of motion are represented in the human brain.