Vestibular function modulates the impact of nGVS on postural control in older adults.

Previous studies have reported an important relationship between increasing age, vestibular impairment, and increased risk of falls. Recently, noisy galvanic vestibular stimulation (nGVS) has been shown to improve postural control in older adults during and potentially following stimulation. However, this effect of nGVS in older adults has not been examined in interaction with the integrity of the vestibular function. We aimed at determining the effect of nGVS on postural control in older adults with and without vestibular impairment and examining the sustained effect of nGVS as compared with a sham stimulation. Thirty-six older adults were assigned to the nGVS group (n = 24) or the sham group (n = 12). In the nGVS group, 12 participants had normal vestibular function and 12 had vestibular impairment. Static postural control was assessed prior to stimulation, during stimulation, and immediately following 30 min of nGVS. Results showed that nGVS induced a significant improvement in sway velocity (P < 0.001) and path length (P < 0.001) compared with sham stimulation. Furthermore, nGVS induced a significantly greater improvement of sway velocity (P < 0.05) and path length (P < 0.05) in older adults with vestibular impairment compared with older adults with normal vestibular function. Improvements in sway velocity (P < 0.001) and path length (P < 0.001) induced by nGVS were sustained immediately following stimulation. These findings suggest that nGVS improves postural control in older adults, and that the effect of nGVS varies depending on the integrity of the vestibular function. Results also show that nGVS effect on postural control, compared with a sham stimulation, can be sustained after the end of stimulation.NEW & NOTEWORTHY The present study is the first study to investigate the impact of vestibular function on the improvement of postural control induced by nGVS in older adults and to compare the improvement of postural control of older adults with and without vestibular impairment. Our results also suggest that nGVS is beneficial for all older adults, and even more for those with a vestibular impairment. Therefore, it could be an approach to reduce falls.

Vestibular Aging Process from 3D Physiological Imaging of the Membranous Labyrinth.

There is no three-dimensional (3D) technique to study the microanatomical structures of the in vivo 3D vestibular membranous labyrinth. Recent two MRI methods using a contrast agent can only depict the low-resolution imaging of endolymphatic hydrops. Therefore, we provide the new precise volume rendering algorithms to create the in vivo 3D vestibular membranous labyrinth images from high-resolution temporal bone low-dose CT data. We also ascertain whether the created 3D microstructure images are reliable in anatomical findings. Secondary, we will analyze the age-related changes of the vestibular membranous labyrinth. These created 3D membranous vestibular images were almost consistent with the appearance, dimensions, areas, and angles from those acquired in previous histological works. The age-related image changes showed the enlarged saccule in females, the enlarged utricle in males, and the dilated tendency of the lateral semicircular duct. These results may correlate to the findings of the previous physiological works on cervical and ocular vestibular evoked myogenic potentials, and gait studies. The age-related balance disorders may be associated with the enlargement of each membranous organ in the vestibule. This new imaging technique now enables visualizing microanatomical changes in the in vivo membranous vestibulum, and these created 3D images may suggest physiological information.

The critical role of vestibular graviception during cognitive-motor development.

Earth's gravity acts both as a mechanical stimulus on the body and as a sensory stimulus to the vestibular organ, which is transmitted into the brain. The vestibular system has been recently highlighted as the cornerstone of the multisensory cortex and of the dorsal hippocampus related to spatial cognition. Consequently, we have hypothesized that the vestibular sensory perception of gravity by the otoliths might also play a crucial role during the first stages of development in both sensorimotor and cognitive functions and the construction and perception of the 'self' and related functions of orientation and navigation. We have investigated an original mouse model (Head Tilted mice, B6Ei.GL-Nox3het/J) suffering from a selective congenital absence of vestibular otolithic gravisensors. We report that mouse pups suffered from a delay in the acquisition of sensorimotor reflexes, spatial olfactory guidance, path integration, and ultrasonic communication, while maternal care remained normal. We demonstrate that development has a critical period dependent on the vestibular otolithic sensory perception of gravity, probably temporally between the somesthetic and visual critical periods. The symptoms expressed by the congenital otolithic-deficient mice are similar to validated mouse models of autism and highlight the significance of vestibular graviception in the pathophysiology of development.

Age-related reweighting of visual and vestibular cues for vertical perception.

As we age, the acuity of our sensory organs declines, which may affect our lifestyle. Sensory deterioration in the vestibular system is typically bilateral and gradual, and could lead to problems with balance and spatial orientation. To compensate for the sensory deterioration, it has been suggested that the brain reweights the sensory information sources according to their relative noise characteristics. For rehabilitation and training programs, it is important to understand the consequences of this reweighting, preferably at the individual subject level. We psychometrically examined the age-dependent reweighting of visual and vestibular cues used in spatial orientation in a group of 32 subjects (age range: 19-76 yr). We asked subjects to indicate the orientation of a line (clockwise or counterclockwise relative to the gravitational vertical) presented within an oriented square visual frame when seated upright or with their head tilted 30° relative to the body. Results show that subjects' vertical perception is biased by the orientation of the visual frame. Both the magnitude of this bias and response variability become larger with increasing age. Deducing the underlying sensory noise characteristics, using Bayesian inference, suggests an age-dependent reweighting of sensory information, with an increasing weight of the visual contextual information. Further scrutiny of the model suggests that this shift in sensory weights is the result of an increase in the noise of the vestibular signal. Our approach quantifies how noise properties of visual and vestibular systems change over the life span, which helps to understand the aging process at the neurocomputational level. NEW & NOTEWORTHY Perception of visual vertical involves a weighted fusion of visual and vestibular tilt cues. Using a Bayesian approach and experimental psychophysics, we quantify how this fusion process changes with age. We show that, with age, the vestibular information is down-weighted whereas the visual weight is increased. This shift in sensory reweighting is primarily due to an age-related increase of the noise of vestibular signals.

Spatial and temporal inhibition of FGFR2b ligands reveals continuous requirements and novel targets in mouse inner ear morphogenesis.

Morphogenesis of the inner ear epithelium requires coordinated deployment of several signaling pathways, and disruptions cause abnormalities of hearing and/or balance. The FGFR2b ligands FGF3 and FGF10 are expressed throughout otic development and are required individually for normal morphogenesis, but their prior and redundant roles in otic placode induction complicates investigation of subsequent combinatorial functions in morphogenesis. To interrogate these roles and identify new effectors of FGF3 and FGF10 signaling at the earliest stages of otic morphogenesis, we used conditional gene ablation after otic placode induction, and temporal inhibition of signaling with a secreted, dominant-negative FGFR2b ectodomain. We show that both ligands are required continuously after otocyst formation for maintenance of otic neuroblasts and for patterning and proliferation of the epithelium, leading to normal morphogenesis of both the cochlear and vestibular domains. Furthermore, the first genome-wide identification of proximal targets of FGFR2b signaling in the early otocyst reveals novel candidate genes for inner ear development and function.

Development of vestibular behaviors in zebrafish.

Most animals orient their bodies with respect to gravity to facilitate locomotion and perception. The neural circuits responsible for these orienting movements have long served as a model to address fundamental questions in systems neuroscience. Though postural control is vital, we know little about development of either balance reflexes or the neural circuitry that produces them. Recent work in a genetically and optically accessible vertebrate, the larval zebrafish, has begun to reveal the mechanisms by which such vestibular behaviors and circuits come to function. Here we highlight recent work that leverages the particular advantages of the larval zebrafish to illuminate mechanisms of postural development, the role of sensation for balance circuit development, and the organization of developing vestibular circuits. Further, we frame open questions regarding the developmental mechanisms for functional circuit assembly and maturation where studying the zebrafish vestibular system is likely to open new frontiers.

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.

Annexin A5 is the Most Abundant Membrane-Associated Protein in Stereocilia but is Dispensable for Hair-Bundle Development and Function.

The phospholipid- and Ca(2+)-binding protein annexin A5 (ANXA5) is the most abundant membrane-associated protein of ~P23 mouse vestibular hair bundles, the inner ear's sensory organelle. Using quantitative mass spectrometry, we estimated that ANXA5 accounts for ~15,000 copies per stereocilium, or ~2% of the total protein there. Although seven other annexin genes are expressed in mouse utricles, mass spectrometry showed that none were present at levels near ANXA5 in bundles and none were upregulated in stereocilia of Anxa5(-/-) mice. Annexins have been proposed to mediate Ca(2+)-dependent repair of membrane lesions, which could be part of the repair mechanism in hair cells after noise damage. Nevertheless, mature Anxa5(-/-) mice not only have normal hearing and balance function, but following noise exposure, they are identical to wild-type mice in their temporary or permanent changes in hearing sensitivity. We suggest that despite the unusually high levels of ANXA5 in bundles, it does not play a role in the bundle's key function, mechanotransduction, at least until after two months of age in the cochlea and six months of age in the vestibular system. These results reinforce the lack of correlation between abundance of a protein in a specific compartment or cellular structure and its functional significance.

The proteome of mouse vestibular hair bundles over development.

Development of the vertebrate hair bundle is a precisely orchestrated event that culminates in production of a tightly ordered arrangement of actin-rich stereocilia and a single axonemal kinocilium. To understand how the protein composition of the bundle changes during development, we isolated bundles from young (postnatal days P4-P6) and mature (P21-P25) mouse utricles using the twist-off method, then characterized their constituent proteins using liquid-chromatography tandem mass spectrometry with data-dependent acquisition. Using MaxQuant and label-free quantitation, we measured relative abundances of proteins in both bundles and in the whole utricle; comparison of protein abundance between the two fractions allows calculation of enrichment in bundles. These data, which are available via ProteomeXchange with identifier PXD002167, will be useful for examining the proteins present in mammalian vestibular bundles and how their concentrations change over development.

Responses to cell loss become restricted as the supporting cells in mammalian vestibular organs grow thick junctional actin bands that develop high stability.

Sensory hair cell (HC) loss is a major cause of permanent hearing and balance impairments for humans and other mammals. Yet, fish, amphibians, reptiles, and birds readily replace HCs and recover from such sensory deficits. It is unknown what prevents replacement in mammals, but cell replacement capacity declines contemporaneously with massive postnatal thickening of F-actin bands at the junctions between vestibular supporting cells (SCs). In non-mammals, SCs can give rise to regenerated HCs, and the bands remain thin even in adults. Here we investigated the stability of the F-actin bands between SCs in ears from chickens and mice and Madin-Darby canine kidney cells. Pharmacological experiments and fluorescence recovery after photobleaching (FRAP) of SC junctions in utricles from mice that express a γ-actin-GFP fusion protein showed that the thickening F-actin bands develop increased resistance to depolymerization and exceptional stability that parallels a sharp decline in the cell replacement capacity of the maturing mammalian ear. The FRAP recovery rate and the mobile fraction of γ-actin-GFP both decreased as the bands thickened with age and became highly stabilized. In utricles from neonatal mice, time-lapse recordings in the vicinity of dying HCs showed that numerous SCs change shape and organize multicellular actin purse strings that reseal the epithelium. In contrast, adult SCs appeared resistant to deformation, with resealing responses limited to just a few neighboring SCs that did not form purse strings. The exceptional stability of the uniquely thick F-actin bands at the junctions of mature SCs may play an important role in restricting dynamic repair responses in mammalian vestibular epithelia.

The candidate splicing factor Sfswap regulates growth and patterning of inner ear sensory organs.

The Notch signaling pathway is thought to regulate multiple stages of inner ear development. Mutations in the Notch signaling pathway cause disruptions in the number and arrangement of hair cells and supporting cells in sensory regions of the ear. In this study we identify an insertional mutation in the mouse Sfswap gene, a putative splicing factor, that results in mice with vestibular and cochlear defects that are consistent with disrupted Notch signaling. Homozygous Sfswap mutants display hyperactivity and circling behavior consistent with vestibular defects, and significantly impaired hearing. The cochlea of newborn Sfswap mutant mice shows a significant reduction in outer hair cells and supporting cells and ectopic inner hair cells. This phenotype most closely resembles that seen in hypomorphic alleles of the Notch ligand Jagged1 (Jag1). We show that Jag1; Sfswap compound mutants have inner ear defects that are more severe than expected from simple additive effects of the single mutants, indicating a genetic interaction between Sfswap and Jag1. In addition, expression of genes involved in Notch signaling in the inner ear are reduced in Sfswap mutants. There is increased interest in how splicing affects inner ear development and function. Our work is one of the first studies to suggest that a putative splicing factor has specific effects on Notch signaling pathway members and inner ear development.

Vestibular development in marsupials and monotremes.

The young of marsupials and monotremes are all born in an immature state, followed by prolonged nurturing by maternal lactation in either a pouch or nest. Nevertheless, the level of locomotor ability required for newborn marsupials and monotremes to reach the safety of the pouch or nest varies considerably: some are transferred to the pouch or nest in an egg (monotremes); others are transferred passively by gravity (e.g. dasyurid marsupials); some have only a horizontal wriggle to make (e.g. peramelid and didelphid marsupials); and others must climb vertically for a long distance to reach the maternal pouch (e.g. diprotodontid marsupials). In the present study, archived sections of the inner ear and hindbrain held in the Bolk, Hill and Hubrecht collections at the Museum für Naturkunde, Berlin, were used to test the relationship between structural maturity of the vestibular apparatus and the locomotor challenges that face the young of these different mammalian groups. A system for staging different levels of structural maturity of the vestibular apparatus was applied to the embryos, pouch young and hatchlings, and correlated with somatic size as indicated by greatest body length. Dasyurids are born at the most immature state, with the vestibular apparatus at little more than the otocyst stage. Peramelids are born with the vestibular apparatus at a more mature state (fully developed semicircular ducts and a ductus reuniens forming between the cochlear duct and saccule, but no semicircular canals). Diprotodontids and monotremes are born with the vestibular apparatus at the most mature state for the non-eutherians (semicircular canals formed, maculae present, but vestibular nuclei in the brainstem not yet differentiated). Monotremes and marsupials reach the later stages of vestibular apparatus development at mean body lengths that lie within the range of those found for laboratory rodents (mouse and rat) reaching the same vestibular stage.

In vivo analysis of Lrig genes reveals redundant and independent functions in the inner ear.

Lrig proteins are conserved transmembrane proteins that modulate a variety of signaling pathways from worm to humans. In mammals, there are three family members - Lrig1, Lrig2, and Lrig3--that are defined by closely related extracellular domains with a similar arrangement of leucine rich repeats and immunoglobulin domains. However, the intracellular domains show little homology. Lrig1 inhibits EGF signaling through internalization and degradation of ErbB receptors. Although Lrig3 can also bind ErbB receptors in vitro, it is unclear whether Lrig2 and Lrig3 exhibit similar functions to Lrig1. To gain insights into Lrig gene functions in vivo, we compared the expression and function of the Lrigs in the inner ear, which offers a sensitive system for detecting effects on morphogenesis and function. We find that all three family members are expressed in the inner ear throughout development, with Lrig1 and Lrig3 restricted to subsets of cells and Lrig2 expressed more broadly. Lrig1 and Lrig3 overlap prominently in the developing vestibular apparatus and simultaneous removal of both genes disrupts inner ear morphogenesis. This suggests that these two family members act redundantly in the otic epithelium. In contrast, although Lrig1 and Lrig2 are frequently co-expressed, Lrig1(-/-);Lrig2(-/-) double mutant ears show no enhanced structural abnormalities. At later stages, Lrig1 expression is sustained in non-sensory tissues, whereas Lrig2 levels are enhanced in neurons and sensory epithelia. Consistent with these distinct expression patterns, Lrig1 and Lrig2 mutant mice exhibit different forms of impaired auditory responsiveness. Notably, Lrig1(-/-);Lrig2(-/-) double mutant mice display vestibular deficits and suffer from a more severe auditory defect that is accompanied by a cochlear innervation phenotype not present in single mutants. Thus, Lrig genes appear to act both redundantly and independently, with Lrig2 emerging as the most functionally distinct family member.

Evaluation and treatment of vestibular dysfunction in children.

INTRODUCTION: The effect of vestibular dysfunction since birth is more debilitating than that attained later in life, and unlike adults, children with vestibular dysfunction since or shortly after birth do not recover function without intervention. PURPOSE: The purpose of this report is to provide an overview of the etiology of vestibular dysfunction in children as well as the related impairments, and to describe testing methods and evidence based interventions to ameliorate the vestibular related impairments in children. SUMMARY: In recent years, investigations have revealed that vestibular dysfunction is more common in children than previously thought, with consequent impairments in motor development, balance and reading abilities. The dysfunction may be due to central or peripheral lesions, each with distinct presentation of symptoms and test results. Common etiologies and clinical presentation of vestibular dysfunction in children are reviewed; appropriate screening and diagnostic techniques and efficacious medical and rehabilitation interventions are presented. CONCLUSION: Despite advances in clinical and diagnostic testing of vestibular function in children and infants, testing of vestibular function is not typically done. Comprehensive testing of signs and symptoms is critical for diagnosis and implementation of appropriate interventions.

MRI analysis of cerebellar and vestibular developmental phenotypes in Gbx2 conditional knockout mice.

PURPOSE: Our aim in this study was to apply three-dimensional MRI methods to analyze early postnatal morphological phenotypes in a Gbx2 conditional knockout (Gbx2-CKO) mouse that has variable midline deletions in the central cerebellum, reminiscent of many human cerebellar hypoplasia syndromes. METHODS: In vivo three-dimensional manganese-enhanced MRI at 100-µm isotropic resolution was used to visualize mouse brains between postnatal days 3 and 11, when cerebellum morphology undergoes dramatic changes. Deformation-based morphometry and volumetric analysis of manganese-enhanced MRI images were used to, respectively, detect and quantify morphological phenotypes in Gbx2-CKO mice. Ex vivo micro-MRI was performed after perfusion-fixation with supplemented gadolinium for higher resolution (50-µm) analysis. RESULTS: In vivo manganese-enhanced MRI and deformation-based morphometry correctly identified known cerebellar defects in Gbx2-CKO mice, and novel phenotypes were discovered in the deep cerebellar nuclei and the vestibulo-cerebellum, both validated using histology. Ex vivo micro-MRI revealed subtle phenotypes in both the vestibulo-cerebellum and the vestibulo-cochlear organ, providing an interesting example of complementary phenotypes in a sensory organ and its associated brain region. CONCLUSION: These results show the potential of three-dimensional MRI for detecting and analyzing developmental defects in mouse models of neurodevelopmental diseases.

Effective sensory modality activating an escape triggering neuron switches during early development in zebrafish.

Developing nervous systems grow to integrate sensory signals from different modalities and to respond through various behaviors. Here, we examined the development of escape behavior in zebrafish [45-170 h postfertilization (hpf)] to study how developing sensory inputs are integrated into sensorimotor circuits. Mature fish exhibit fast escape upon both auditory/vestibular (AV) and head-tactile stimuli. Newly hatched larvae, however, do not respond to AV stimuli before 75 hpf. Because AV-induced fast escape in mature fish is triggered by a pair of hindbrain neurons known as Mauthner (M) cells, we studied functional development of the M-cell circuit accounting for late acquisition of AV-induced escape. In fast escape elicited by head-directed water jet, minimum onset latency decreased throughout development (5 ms at 45-59 hpf, 3 ms after 75 hpf). After 75 hpf, lesioning the otic vesicle (OV) to eliminate AV input resulted in loss of short-latency (<5 ms) fast escape, whereas ablation of the sensory trigeminal ganglion (gV) to block head-tactile input did not. Before 75 hpf, however, fast escape persisted after OV lesion but disappeared after gV ablation. Laser ablation of the M-cell and Ca²âº imaging of the M-cell during escape demonstrated that M-cell firing is required to initiate short-latency fast escapes at every developmental stage and further suggest that head-tactile input activates the M-cell before 75 hpf, but that after this point AV input activates the M-cell instead. Thus, a switch in the effective sensory input to the M-cells mediates the acquisition of a novel modality for initiating fast escape.

Transforming the vestibular system one molecule at a time: the molecular and developmental basis of vertebrate auditory evolution.

We review the molecular basis of auditory development and evolution. We propose that the auditory periphery (basilar papilla, organ of Corti) evolved by transforming a newly created and redundant vestibular (gravistatic) endorgan into a sensory epithelium that could respond to sound instead of gravity. Evolution altered this new epithelia's mechanoreceptive properties through changes of hair cells, positioned the epithelium in a unique position near perilymphatic space to extract sound moving between the round and the oval window, and transformed its otolith covering into a tympanic membrane. Another important step in the evolution of an auditory system was the evolution of a unique set of "auditory neurons" that apparently evolved from vestibular neurons. Evolution of mammalian auditory (spiral ganglion) neurons coincides with GATA3 being a transcription factor found selectively in the auditory afferents. For the auditory information to be processed, the CNS required a dedicated center for auditory processing, the auditory nuclei. It is not known whether the auditory nucleus is ontogenetically related to the vestibular or electroreceptive nuclei, two sensory systems found in aquatic but not in amniotic vertebrates, or a de-novo formation of the rhombic lip in line with other novel hindbrain structures such as pontine nuclei. Like other novel hindbrain structures, the auditory nuclei express exclusively the bHLH gene Atoh1, and loss of Atoh1 results in loss of most of this nucleus in mice. Only after the basilar papilla, organ of Corti evolved could efferent neurons begin to modulate their activity. These auditory efferents most likely evolved from vestibular efferent neurons already present. The most simplistic interpretation of available data suggest that the ear, sensory neurons, auditory nucleus, and efferent neurons have been transformed by altering the developmental genetic modules necessary for their development into a novel direction conducive for sound extraction, conduction, and processing.

Exposure to hypergravity during specific developmental periods differentially affects metabolism and vestibular reactions in adult C57BL /6j mice.

The development of the posturo-motor control of movement is conditioned by Earth's gravity. Missing or altered gravity during the critical periods of development delays development and induces durable changes in the vestibular, cerebellar, or muscular structures, but these are not consistently mirrored at a functional level. The differences in the time schedule of vestibular and motor development could contribute to this inconstancy. To investigate the influence of gravity on the development of vestibular and locomotor functions, we analysed the performance of adult mice subjected to hypergravity during the time covering either the vestibular or locomotor development. The mice were centrifuged at 2 g from embryonic day (E) 0 to postnatal day (P) 10 (PRE), from P10 to P30 (POST), from E0 to P30 (FULL), and from E7 to P21. Their muscular force, anxiety level, vestibular reactions, and aerobic capacity during treadmill training were then evaluated at the age of 2 and 6 months. The performance of young adults varied in relation to the period of exposure to hypergravity. The mice that acquired locomotion in hypergravity (POST and FULL) showed a lower forelimb force and delayed vestibular reactions. The mice centrifuged from conception to P10 (PRE) showed a higher aerobic capacity during treadmill training. The differences in muscular force and vestibular reactions regressed with age, but the metabolic changes persisted. These results confirmed that early exposure to hypergravity induces qualitative changes depending on the period of exposure. They validated, at a functional level, the existence of several critical periods for adaptation to gravity.

Gravity-related critical periods in vestibular and tail development of Xenopus laevis.

Sensory systems are characterized by developmental periods during which they are susceptible to environmental modifications, in particular to sensory deprivation. The experiment, XENOPUS, on Soyuz in 2008 was the fourth space flight experiment since 1993 to explore whether tail and vestibular development of Xenopus laevis has a gravity-related critical period. During this flight, tadpoles were used that had developed either the early hindlimb (stage 47) or forelimb bud (stage 50) at launch of the spacecraft. The results revealed (1) no impact of microgravity on the development of the roll-induced vestibuloocular reflex (rVOR) in both stages and (2) a stage-related sensitivity of tail development to microgravity exposure. These results were combined and compared with observations from space flights on other orbital platforms. The combined data revealed (1) a narrow gravity-related critical period for rVOR development close to the period of the first appearance of the reflex and (2) a longer one for tail development lasting from the early tail bud to the early forelimb bud stage.

Development of spontaneous activity and response properties of primary lagenar neurons in the chick.

Here, we report for the first time developmental changes in spontaneous activity and in response properties of single nerve fibers from the macular chick lagena. Such aspects are important in order to get insight into the functional role of the lagena which remains undetermined. For this purpose, we used intracellular and extracellular single-unit recording techniques in an isolated inner ear preparation from the chicken at ages E15 and P1. At E15, afferent fibers displayed a low irregular spontaneous discharge rate (41 +/- 14 spikes/s, CV = 1.17 +/- 0.1), which was replaced by regular high frequency spontaneous activity at P1 (CV = 0.48 +/- 0.8, 89 +/- 27 spikes/s). During the developmental period including E15, the percentage of silent neurons was 60% while that of P1 was 40%. The synaptic activity was higher at E15 than at P1. The action potential waveform generated at E15 had small amplitude and derivative depolarization, and consequently, a large duration in correlation with respect to action potential waveform at P1 (respectively: 53 +/- 2 vs. 65 +/- 3 mV, 60 +/- 11 vs. 109 +/- 20 mV/ms, 3.6 +/- 0.4 vs. 1.1 +/- 0.12 ms). In addition, we recognized two response dynamics to the injection of current steps: phasic, or rapidly adapting neurons and tonic, or slowly adapting neurons. Our results indicate similar developmental processes for the lagena as described for the vestibular system in other species, in agreement with the known morphological characteristics of this otholitic end organ. The presence of more than one subtype of afferent neuron also correlates with previous reports on vestibular afferents with analogous electrophysiological properties, strongly suggesting the vestibular nature of the lagena.