The Central Network Involved in the Processing of Vestibular Inputs and the Generation of Vestibulosympathetic Reflexes Controlling Blood Pressure in Humans.

The vestibular apparatus is highly specialized for detecting linear and angular acceleration, contributing importantly to perception of our position in the gravitational field and to motion in the three spatial axes. Beginning in the inner ear, spatial information is relayed toward higher cortical regions for processing, though the specific locations at which this action takes place remain somewhat ambiguous. This article aims to highlight brain regions known to be involved in the processing of spatial information, as well as those that contribute to a less widely documented function of the vestibular system-its capacity to regulate blood pressure via vestibulosympathetic reflexes. As we go from lying to standing, there is a proportional increase in muscle sympathetic nerve activity (MSNA) to the legs that prevents the fall in blood pressure associated with the pooling of blood toward the feet. While feedback from baroreceptors is partially responsible, vestibulosympathetic reflexes operate in a feed-forward manner to compensate for postural changes in the gravitational field. The cortical and subcortical network comprising the central sympathetic connectome shares certain elements with the vestibular system, and it is known that vestibular afferents project via the vestibular nuclei to the rostral ventrolateral medulla (RVLM)-the final output nucleus for generating MSNA. Here we consider how vestibular afferents interact with other components of the central sympathetic connectome, with particular emphasis on the potential roles of the insula and dorsolateral prefrontal cortex (dlPFC) as possible core integrative sites for vestibular and higher cortical processes. © 2023 American Physiological Society. Compr Physiol 13:4811-4832, 2023.

Retro-labyrinthine Lesion Site Detected by Galvanic Vestibular Stimulation Elicited Vestibular-evoked Myogenic Potentials in Patients with Auditory Neuropathy.

OBJECTIVE: Auditory neuropathy (AN) is a unique pattern of hearing loss with preservation of hair cell function. The condition is characterized by the presence of otoacoustic emissions (OAE) or cochlear microphonic (CM) responses with severe abnormalities of the auditory brainstem response (ABR). The vestibular branches of the VIII cranial nerve and the structures innervated by it can also be affected. However, the precise lesion sites in the vestibular system are not well characterized in patients with AN. METHODS: The air-conducted sound (ACS) vestibular-evoked myogenic potentials (VEMPs) and galvanic vestibular stimuli (GVS)-VEMPs were examined in 14 patients with AN. RESULTS: On examination of VEMPs (n=14, 28 ears), the absent rates of ACS-cervical VEMP (cVEMP), ACS-ocular VEMP (oVEMP), GVS-cVEMP, GVS-oVEMP and caloric test were 92.9% (26/28), 85.7% (24/28), 67.9% (19/28), 53.6% (15/28), and 61.5% (8/13), respectively. Impaired functions of the saccule, inferior vestibular nerve, utricle, superior vestibular nerve, and horizontal semicircular canal were found in 25.0% (7/28), 67.9% (19/28), 32.1% (9/28), 53.6% (15/28) and 61.5% (8/13) patients, respectively. On comparing the elicited VEMPs parameters of AN patients with those of normal controls, both ACS-VEMPs and GVS-VEMPs showed abnormal results in AN patients (such as, lower presence rates, elevated thresholds, prolonged latencies, and decreased amplitudes). CONCLUSION: The study suggested that patients with AN often have concomitant vestibular disorders. Retro-labyrinthine lesions were more frequently observed in this study. GVS-VEMPs combined with ACS-VEMPs may help identify the lesion sites and facilitate detection of areas of vestibular dysfunction in these patients.

Arachnoid Cysts of the Internal Auditory Canal: Multiplanar Magnetic Resonance Imaging With Audio-Vestibular Correlates.

OBJECTIVES/HYPOTHESIS: To investigate prevalence, radiological characteristics, and functional correlates of arachnoid cysts (AC) of the internal auditory canal (IAC) region, including associations of nerve compression with auditory/vestibular symptoms and asymmetrical audiogram or vestibular testing. STUDY DESIGN: Retrospective study. METHODS: T2-weighted magnetic resonance imaging (MRI) studies of IACs were retrospectively analyzed from 1247 patients with asymmetric auditory or vestibular symptoms. Patients with radiological findings of AC of the IAC were identified. Multiplanar analysis was used to analyze cyst position in the IAC and assess nerve displacement or compression. Size, position, and presence of nerve compression were correlated with symptoms. RESULTS: Twenty-four patients had a cyst in the middle or fundus in the IAC. Diameter (P = .04) and position (P = .002) of AC were associated with symptoms. Sagittal analyses identified displacement versus compression (P = .003) more reliably than axial imaging. Symptom laterality was associated with the site of radiological abnormality. Vestibular nerve compression was associated with vertigo (P = .0001), and cochlear nerve compression was associated with auditory symptoms (P < .0001). CONCLUSIONS: In a retrospective series of patients undergoing MRI of IACs for asymmetric auditory or vestibular impairment, clinical symptom profile correlated with blinded assessment of IAC lesions. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2323-2331, 2021.

Effects of vestibular neurectomy and neural compensation on head movements in patients undergoing vestibular schwannoma resection.

The vestibular system is vital for maintaining balance and stabilizing gaze and vestibular damage causes impaired postural and gaze control. Here we examined the effects of vestibular loss and subsequent compensation on head motion kinematics during voluntary behavior. Head movements were measured in vestibular schwannoma patients before, and then 6 weeks and 6 months after surgical tumor removal, requiring sectioning of the involved vestibular nerve (vestibular neurectomy). Head movements were recorded in six dimensions using a small head-mounted sensor while patients performed the Functional Gait Assessment (FGA). Kinematic measures differed between patients (at all three time points) and normal subjects on several challenging FGA tasks, indicating that vestibular damage (caused by the tumor or neurectomy) alters head movements in a manner that is not normalized by central compensation. Kinematics measured at different time points relative to vestibular neurectomy differed substantially between pre-operative and 6-week post-operative states but changed little between 6-week and > 6-month post-operative states, demonstrating that compensation affecting head kinematics is relatively rapid. Our results indicate that quantifying head kinematics during self-generated gait tasks provides valuable information about vestibular damage and compensation, suggesting that early changes in patient head motion strategy may be maladaptive for long-term vestibular compensation.

Diagnostic and therapeutic strategies for Meniere's disease of the Japan Society for Equilibrium Research.

OBJECTIVE: We provided diagnostic and therapeutic strategies for Meniere's disease in accordance with Japanese Clinical Practice Guideline of Meniere's disease and delayed endolymphatic hydrops 2nd ed. Tokyo: Kanehara Shuppan; 2020 edited by the Japan Society for Equilibrium Research. METHODS: The Committee for Clinical Practice Guidelines was entrusted with a review of the scientific literature on the above topic. Clinical Questions (CQs) concerning the treatment for Meniere's disease were produced, and the literature according to each of them including CQ was searched. The recommendations are based on the literature review and the expert opinion of a subcommittee. RESULTS: Diagnosis criteria of Meniere's disease are classified into Meniere's disease with typical cochlear and vestibular symptoms, and atypical Meniere's disease with either cochlear symptoms or vestibular symptoms. Treatment of Meniere's disease was composed of lifestyle changes, medications such as anti-vertigo drugs and diuretics, middle ear positive pressure treatment, and selective destruction of the vestibule. CONCLUSION: Meniere's disease is diagnosed based on clinical histories and examination findings after processes of differential diagnosis. Treatment option of the disease should be selected in order of invasiveness, according to the severity of the disease and the response to each treatment.

Topography of the lesion in idiopathic sudden sensorineural hearing loss.

INTRODUCTION: Etiology of ISSNHL includes cessation of vascular perfusion, viral infection and cochlear membrane injury. Precise location of injury should be defined for a target-oriented treatment. Vestibular complaints in ISSNHL are hypothesized as involvement of vestibule. Vestibular complaints can be either due to involvement of inner ear or neural tract at any level. OBJECTIVES: In the present study we aimed to demonstrate involvement of vestibular organs in the absence of vestibular symptoms. It was aimed to evaluate superior and inferior vestibular neural pathways. METHODS: c-vemp and o-vemp were applied to patients suffering ISSNHL without vertigo. Pure tone averages, audiogram configurations, degree of hearing loss were analyzed. Latencies of P1 and N1 waves, amplitudes of P1-N1 waves were evaluated. Asymmetrical vemp wave patterns were compared between two ears regarding difference of PTA. RESULTS: Latencies of c-vemp waves were longer and amplitudes were smaller. o-vemp parameters were similar on both sides. Positive correlation was observed between c-vemp latencies and degree hearing loss. CONCLUSION: Inferior vestibular nerve pathway is affected in the absence of vertigo in ISSNHL with spared superior vestibular nerve pathway. Damage in IVN pathway correlates with degree of ISSNHL.

Selective targeting of unipolar brush cell subtypes by cerebellar mossy fibers.

In vestibular cerebellum, primary afferents carry signals from single vestibular end organs, whereas secondary afferents from vestibular nucleus carry integrated signals. Selective targeting of distinct mossy fibers determines how the cerebellum processes vestibular signals. We focused on vestibular projections to ON and OFF classes of unipolar brush cells (UBCs), which transform single mossy fiber signals into long-lasting excitation or inhibition respectively, and impact the activity of ensembles of granule cells. To determine whether these contacts are indeed selective, connectivity was traced back from UBC to specific ganglion cell, hair cell and vestibular organ subtypes in mice. We show that a specialized subset of primary afferents contacts ON UBCs, but not OFF UBCs, while secondary afferents contact both subtypes. Striking anatomical differences were observed between primary and secondary afferents, their synapses, and the UBCs they contact. Thus, each class of UBC functions to transform specific signals through distinct anatomical pathways.

Neural substrates, dynamics and thresholds of galvanic vestibular stimulation in the behaving primate.

Galvanic vestibular stimulation (GVS) uses the external application of electrical current to selectively target the vestibular system in humans. Despite its recent popularity for the assessment/treatment of clinical conditions, exactly how this non-invasive tool activates the vestibular system remains an open question. Here we directly investigate single vestibular afferent responses to GVS applied to the mastoid processes of awake-behaving monkeys. Transmastoid GVS produces robust and parallel activation of both canal and otolith afferents. Notably, afferent activation increases with intrinsic neuronal variability resulting in constant GVS-evoked neuronal detection thresholds across all afferents. Additionally, afferent tuning differs for GVS versus natural self-motion stimulation. Using a stochastic model of repetitive activity in afferents, we largely explain the main features of GVS-evoked vestibular afferent dynamics. Taken together, our results reveal the neural substrate underlying transmastoid GVS-evoked perceptual, ocular and postural responses-information that is essential to advance GVS applicability for biomedical uses in humans.

Frequency-dependent deficits in head steadiness in patients with nonspecific neck pain.

Motor control impairments are reported in patients with nonspecific neck pain but the particular deficits in underlying regulatory systems are not known. Head steadiness is controlled both by voluntary and reflex systems that are predominantly effective within different frequency intervals. The aim of the present study was to investigate within which frequency range(s) potential motor control deficits may reside. The ability to keep the head stationary in space in response to unpredictable perturbations was tested in 71 patients with nonspecific neck pain and 17 healthy controls. Participants were exposed to pseudorandom horizontal rotations across 10 superimposed frequencies (0.185-4.115 Hz) by means of an actuated chair in three conditions; with a visual reference, and without vision with, and without a cognitive task. Below 1 Hz, patients kept the head less stable in space compared to healthy controls. Between 1 and 2 Hz, the head was stabilized on the trunk in both groups. Patients kept the head more stable relative to the trunk than relative to space compared to healthy controls. This was interpreted as higher general neck muscle co-activation in patients, which may be explained by altered voluntary control, or/and upregulated gamma motor neuron activity which increases the contribution of reflex-mediated muscle activation. Alternatively, increased muscle activity is secondary to vestibular deficits.

Discharge properties of morphologically identified vestibular neurons recorded during horizontal eye movements in the goldfish.

Computational capability and connectivity are key elements for understanding how central vestibular neurons contribute to gaze-stabilizing eye movements during self-motion. In the well-characterized and segmentally distributed hindbrain oculomotor network of goldfish, we determined afferent and efferent connections along with discharge patterns of descending octaval nucleus (DO) neurons during different eye motions. Based on activity correlated with horizontal eye and head movements, DO neurons were categorized into two complementary groups that either increased discharge during both contraversive (type II) eye (e) and ipsiversive (type I) head (h) movements (eIIhI) or vice versa (eIhII). Matching time courses of slow-phase eye velocity and corresponding firing rates during prolonged visual and head rotation suggested direct causality in generating extraocular motor commands. The axons of the dominant eIIhI subgroup projected either ipsi- or contralaterally and terminated in the abducens nucleus, Area II, and Area I with additional recurrent collaterals of ipsilaterally projecting neurons within the parent nucleus. Distinct feedforward commissural pathways between bilateral DO neurons likely contribute to the generation of eye velocity signals in eIhII cells. The shared contribution of DO and Area II neurons to eye velocity storage likely represents an ancestral condition in goldfish that is clearly at variance with the task separation between mammalian medial vestibular and prepositus hypoglossi neurons. This difference in signal processing between fish and mammals might correlate with a larger repertoire of visuo-vestibular-driven eye movements in the latter species that potentially required a shift in sensitivity and connectivity within the hindbrain-cerebello-oculomotor network. NEW & NOTEWORTHY We describe the structure and function of neurons within the goldfish descending octaval nucleus. Our findings indicate that eye and head velocity signals are processed by vestibular and Area II velocity storage integrator circuitries whereas the velocity-to-position Area I neural integrator generates eye position solely. This ancestral condition differs from that of mammals, in which vestibular neurons generally lack eye position signals that are processed and stored within the nucleus prepositus hypoglossi.

Vestibular modulation of muscle sympathetic nerve activity assessed over a 100-fold frequency range of sinusoidal galvanic vestibular stimulation.

We have previously shown that sinusoidal galvanic vestibular stimulation (sGVS), delivered at 0.2-2.0 Hz, evokes a partial entrainment of muscle sympathetic nerve activity (MSNA). Moreover, at lower frequencies of stimulation (0.08-0.18 Hz) sGVS produces two peaks of modulation: one (primary) peak associated with the positive peak of the sinusoidal stimulus and a smaller (secondary) peak associated with the trough. Here we assessed whether sGVS delivered at 0.05 Hz causes a more marked modulation of MSNA than at higher frequencies and tested the hypothesis that the primary and secondary peaks are of identical amplitude because of the longer cycle length. MSNA was recorded via tungsten microelectrodes inserted into the left peroneal nerve in 11 seated subjects. Bipolar binaural sGVS (±2 mA, 100 cycles) was applied to the mastoid processes at 0.05, 0.5, and 5.0 Hz (500 cycles). Cross-correlation analysis revealed two bursts of modulation of MSNA for each cycle at 0.05 and 0.5 Hz but only one at 5 Hz. There was a significant inverse linear relationship between vestibular modulation (primary peak) and frequency (P < 0.0001), with the amplitudes of the peaks being highest at 0.05 Hz. Moreover, the secondary peak at this frequency was not significantly different from the primary peak. These results indicate that vestibular modulation of MSNA operates over a large range of frequencies but is greater at lower frequencies of sGVS. We conclude that the vestibular apparatus, through its influence on muscle sympathetic outflow, preferentially contributes to the control of blood pressure at low frequencies. NEW & NOTEWORTHY Vestibulosympathetic reflexes have been documented in experimental animals and humans. Here we show that sinusoidal galvanic vestibular stimulation, a means of selectively exciting vestibular afferents in humans, induces greater modulation of muscle sympathetic nerve activity when delivered at a very low frequency (0.05 Hz) than at 0.5 or 5.0 Hz.

Phase-locking of irregular guinea pig primary vestibular afferents to high frequency (>250 Hz) sound and vibration.

Phase-locking of cochlear neurons to sound has been of great value in understanding cochlear transduction. Phase-locking has also been reported previously in irregular vestibular afferents, but detailed information about it is sparse. We measured the phase-locking of guinea pig irregular otolithic neurons and canal neurons (after a semicircular canal dehiscence allowed them to respond) to both sound and vibration stimuli. Irregular vestibular afferents from both otoliths and canals have a range of preferred phase angles which systematically increase as frequency is increased from 250 Hz to above 1000 Hz. Surprisingly vestibular afferents show more precise phase-locking than comparable auditory afferents as reported by Palmer and Russell (1986), and they do so up to higher frequencies. This high precision implies a very sharp, fast threshold for evoking an action potential with minimal variability, and so has implications for the current controversy about hair-cell-afferent transmission in the vestibular system. Following recent evidence, we suggest that potassium in the unique type I-calyx synapse may be a major factor in generating this very precise phase-locking.

Vestibular and corticospinal control of human body orientation in the gravitational field.

Body orientation with respect to the direction of gravity changes when we lean forward from upright standing. We tested the hypothesis that during upright standing, the nervous system specifies the referent body orientation that defines spatial thresholds for activation of multiple muscles across the body. To intentionally lean the body forward, the system is postulated to transfer balance and stability to the leaned position by monotonically tilting the referent orientation, thus increasing the activation thresholds of ankle extensors and decreasing their activity. Consequently, the unbalanced gravitational torque would start to lean the body forward. With restretching, ankle extensors would be reactivated and generate increasing electromyographic (EMG) activity until the enhanced gravitational torque would be balanced at a new posture. As predicted, vestibular influences on motoneurons of ankle extensors evaluated by galvanic vestibular stimulation were smaller in the leaned compared with the upright position, despite higher tonic EMG activity. Defacilitation of vestibular influences was also observed during forward leaning when the EMG levels in the upright and leaned position were equalized by compensating the gravitational torque with a load. The vestibular system is involved in the active control of body orientation without directly specifying the motor outcome. Corticospinal influences originating from the primary motor cortex evaluated by transcranial magnetic stimulation remained similar at the two body postures. Thus, in contrast to the vestibular system, the corticospinal system maintains a similar descending facilitation of motoneurons of leg muscles at different body orientations. The study advances the understanding of how body orientation is controlled. NEW & NOTEWORTHY The brain changes the referent body orientation with respect to gravity to lean the body forward. Physiologically, this is achieved by shifts in spatial thresholds for activation of ankle muscles, which involves the vestibular system. Results advance the understanding of how the brain controls body orientation in the gravitational field. The study also extends previous evidence of empirical control of motor function, i.e., without the reliance on model-based computations and direct specification of motor outcome.

Vestibular-related eye movements in the rat following selective electrical stimulation of the vestibular sensors.

Rats are the most commonly used species in the neurosciences; however, little is known about the effects of selective electrical stimulation of individual vestibular sensors, on their eye movements. This limits their use to study the effects of vestibular stimulation on the brain, and their use in further exploring novel technologies such as artificial vestibular implants. We describe the effects of electrical stimulation of each vestibular sensor on vestibular-related eye movement in rats and compared the results to other species. We demonstrated that each sensor is responsible for specific bilateral eye movements. We found that the eye movements in rats differed from other species. Although the results were similar when stimulating the horizontal canal ampulla, differences appeared when stimulating the vertical canal sensors. During utricular stimulation, the ipsilateral eye moved dorsally in most cases, while the contralateral eye usually moved either caudally, or in extorsion. Saccular stimulation usually moved the ipsilateral eye dorsally or ventrally, while the contralateral eye usually moved ventrally or caudally. This study provides the first data on the application of selective electrical vestibular stimulation in the rat to the study of vestibular-related eye movements.

A different ultrastructural face of ribbon synapses in the rat retina.

Ribbon synapses located exclusively within retinal, cochlear and vestibular connections belong to the most interesting cellular structures but their molecular nature and functions had remained unclear. The study has provided a descriptive morphological analysis of rat eye ribbon synapses using high-resolution transmission electron microscopy (TEM). An original collection of untypical, rarely present in the literature sagittal or tangential sections through the single RIBEYE domain of the particular ribbon have been delivered.

Single neuron activity and c-Fos expression in the rat striatum following electrical stimulation of the peripheral vestibular system.

Connections between the vestibular system and the basal ganglia have been postulated since the early 20th century. However, the results of electrophysiological studies investigating neuronal responses to electrical stimulation of the vestibular system have been inconsistent. The aim of this study was to investigate the effects of electrical stimulation of the vestibular labyrinth on single neuron activity and c-Fos expression in the rat striatum. We used electrical stimulation of the vestibular labyrinth (various intensities delivered to the round window) to examine the electrophysiological response of striatal neurons and c-Fos expression. From 507 single neurons recorded (n = 20 rats), no vestibular-responsive neuron was found at 1× and 2× the nystagmus threshold; however, 6 neurons were found at 3× the threshold. These neurons were found bilaterally, with a response latency of ~50 msec from the end of the stimulus. For the c-Fos study, the number of neurons expressing c-Fos was quantified using stereological methods. Stimulation at 2× the threshold for nystagmus (n = 5 rats) resulted in a significant decrease in the number of neurons expressing c-Fos in the bilateral striatum compared to both the sham control group (n = 5) and the lower stimulus intensity group (n = 5) (P ≤ 0.0001 for both). The results of this study demonstrate that: (1) some single striatal neurons respond to electrical vestibular stimulation, however, these responses are circumscribed and infrequent; (2) electrical stimulation of the vestibular labyrinth results in a decrease in the number of striatal neurons expressing c-Fos, in a current-dependent manner.

The Degeneration of the Vestibular Efferent Neurons After Intratympanic Gentamicin Administration.

Intratympanic gentamicin (ITG) has been used to treat refractory Ménière's disease. Disequilibrium after ITG was still a challenge for some patients, and the underlying mechanism is poorly understood. Our previous study demonstrated that gentamicin distributed in the bilateral vestibular efferent neurons (VEN) after ITG; however, does it lead to VEN damage and cause further disequilibrium in patients following ITG? In this study, we observed severe damaged gentamicin-positive neurons of VEN and severe fractured myelin layer plates around neural fibers when viewed under transmission electron microscopy at day 3 after ITG. At day 30, neurons of VEN presented with relatively normal structures. Compared with the control group, the total number of choline acetyltransferase (CHAT) immunolabeling neurons in bilateral VEN showed a significant decrease both at day 3 and day 30. However, there was no significant difference in the total number of CHAT immunolabeling neurons between day 3 and day 30. It indicates that gentamicin is not only retrogradely transported into bilateral VEN, but also results in the degeneration of VEN after ITG. These findings may be related to patients' disequilibrium symptom after ITG. Furthermore, we speculate that VEN may play a role in vestibular compensation.

Electrophysiological Properties of Rat Vestibular Labyrinth and Their Effect on Parameters of Transmitted Voltage Pulses.

We propose a new approach to optimization of electrical stimulation of the vestibular nerve and improving the transfer function of vestibular implant. A mathematical model of the vestibular organ is developed based on its anatomy, the model premises, 3D-analysis of MRI and CT images, and mathematical description of physical processes underlying propagation of alternating electric current across the tissues of vestibular labyrinth. This approach was tested in vitro on the rat vestibular apparatus and had been examined anatomically prior to the development of its mathematical model and equivalent electrical circuit. The experimental and theoretical values of changes of the gain-phase characteristics of vestibular tissues in relation to location of the reference electrode obtained in this study can be used to optimize the electrical stimulation of vestibular nerve.

Perception of the dynamic visual vertical during sinusoidal linear motion.

The vestibular system provides information for spatial orientation. However, this information is ambiguous: because the otoliths sense the gravitoinertial force, they cannot distinguish gravitational and inertial components. As a consequence, prolonged linear acceleration of the head can be interpreted as tilt, referred to as the somatogravic effect. Previous modeling work suggests that the brain disambiguates the otolith signal according to the rules of Bayesian inference, combining noisy canal cues with the a priori assumption that prolonged linear accelerations are unlikely. Within this modeling framework the noise of the vestibular signals affects the dynamic characteristics of the tilt percept during linear whole-body motion. To test this prediction, we devised a novel paradigm to psychometrically characterize the dynamic visual vertical-as a proxy for the tilt percept-during passive sinusoidal linear motion along the interaural axis (0.33 Hz motion frequency, 1.75 m/s2 peak acceleration, 80 cm displacement). While subjects (n=10) kept fixation on a central body-fixed light, a line was briefly flashed (5 ms) at different phases of the motion, the orientation of which had to be judged relative to gravity. Consistent with the model's prediction, subjects showed a phase-dependent modulation of the dynamic visual vertical, with a subject-specific phase shift with respect to the imposed acceleration signal. The magnitude of this modulation was smaller than predicted, suggesting a contribution of nonvestibular signals to the dynamic visual vertical. Despite their dampening effect, our findings may point to a link between the noise components in the vestibular system and the characteristics of dynamic visual vertical.NEW & NOTEWORTHY A fundamental question in neuroscience is how the brain processes vestibular signals to infer the orientation of the body and objects in space. We show that, under sinusoidal linear motion, systematic error patterns appear in the disambiguation of linear acceleration and spatial orientation. We discuss the dynamics of these illusory percepts in terms of a dynamic Bayesian model that combines uncertainty in the vestibular signals with priors based on the natural statistics of head motion.

Delayed Otolith Development Does Not Impair Vestibular Circuit Formation in Zebrafish.

What is the role of normally patterned sensory signaling in development of vestibular circuits? For technical reasons, including the difficulty in depriving animals of vestibular inputs, this has been a challenging question to address. Here we take advantage of a vestibular-deficient zebrafish mutant, rock solo AN66 , in order to examine whether normal sensory input is required for formation of vestibular-driven postural circuitry. We show that the rock solo AN66 mutant is a splice site mutation in the secreted glycoprotein otogelin (otog), which we confirm through both whole genome sequencing and complementation with an otog early termination mutant. Using confocal microscopy, we find that elements of postural circuits are anatomically normal in rock solo AN66 mutants, including hair cells, vestibular ganglion neurons, and vestibulospinal neurons. Surprisingly, the balance and postural deficits that are readily apparent in younger larvae disappear around 2 weeks of age. We demonstrate that this behavioral recovery follows the delayed development of the anterior (utricular) otolith, which appears around 14 days post-fertilization (dpf), compared to 1 dpf in WT. These findings indicate that utricular signaling is not required for normal structural development of the inner ear and vestibular nucleus neurons. Furthermore, despite the otolith's developmental delay until well after postural behaviors normally appear, downstream circuits can drive righting reflexes within ∼1-2 days of its arrival, indicating that vestibular circuit wiring is not impaired by a delay in patterned activity. The functional recovery of postural behaviors may shed light on why humans with mutations in otog exhibit only subclinical vestibular deficits.