Receptor Organs Research Articles

The vomeronasal organ is not involved in the perception of endogenous odors

Chemosensory-based communication is a vital signaling tool in most species, and evidence has recently emerged in support of the notion that humans also use social chemosignals (so-called pheromones) to communicate. An ongoing controversy does exist, however, concerning the receptor organ through which these chemicals are processed. There is a widespread belief that the vomeronasal organ (VNO) is responsible for processing social chemosignals in humans. Here we demonstrate that functional occlusion of the VNO does not change the percept of, sensitivity toward, or functional neuronal processing of a putative human pheromone. Perithreshold and suprathreshold perception of the endogenous chemical androstadienone (AND) were compared, as were positron emission tomography brain activations evoked by AND when the VNO was either occluded or left open. In addition, we compared sensitivity to AND in subjects with an identifiable VNO to those in whom no VNO could be detected. Thus we could examine the effects of the VNO at several different levels of processing. Occlusion or absence of the VNO did not affect either the perceptual measurements or the functional processing of the putative human pheromone, AND. These results provide strong evidence that the human VNO has no obvious function. Pheromonal communication in humans may be conveyed via the main olfactory system.

Imaging electrical resonance in hair cells

The mechanosensory hair cells of many auditory receptor organs are tuned by an electrical resonance that increases their responses to stimulation over a narrow band of frequencies. The small oscillations of membrane potential characteristic of this phenomenon have previously been detectable only through intracellular electrode measurements, which are laborious and preclude analysis at the level of an entire sensory organ. We used a voltage-sensitive dye to image hair-cell electrical resonance in an intact preparation of the bullfrog's sacculus, a receptor organ sensitive to low-frequency seismic and auditory stimuli. Imaging revealed distinct populations of hair cells whose resonant response varied with the frequency of transepithelial electrical stimulation. Most of the hair cells in the saccular epithelium in vitro were electrically tuned to stimulation at 25-50 Hz. The frequency dependence of the fluorescence signal was sensitive to pharmacological blockade of large-conductance Ca(2+)-sensitive K(+) channels and to enzymatic digestion. At an elevated concentration of Ca(2+), we observed transient fluorescence signals that probably represented action potentials. The stroboscopic imaging and analysis techniques described here present a general approach for studying subthreshold oscillations in electrically excitable cells.

The perception threshold counterpart to dynamic and static mechanical allodynia assessed using von Frey filaments in peripheral neuropathic pain patients

Background and aim Pain due to a usually non-painful mechanical stimulus, mechanical allodynia, is an oppressive symptom in subgroups of patients with neuropathic pain. Dynamic mechanical allodynia (DMA) is evoked by a normally innocuous light moving mechanical stimulus on the skin and static mechanical allodynia (SMA) by a sustained, normally innocuous pressure against the skin. DMA is claimed to be mediated by myelinated fibres and SMA by C-fibres. Also A-delta fibres have been implicated in the static subtype. A low intensity vertically applied stimulus of 1 second (s) is expected to activate predominantly rapidly adapting A-beta mechanoreceptors thus recruiting the same peripheral substrate as a horizontally moving brush on top of the skin. In patients with SMA we assumed an activation of C- but also A-delta fibres from a static 10 s von Frey filament stimulus. The aim was to investigate if DMA and SMA could be assessed at perception threshold level using short or longer lasting usually non-painful von Frey filament prodding of the neuropathic skin. Patients and methods Eighteen patients with painful unilateral partial peripheral traumatic nerve injury suffering from SMA ( n = 9) and/or DMA ( n = 18) in a limb were studied. A compression/ischemia-induced (differential) nerve block in conjunction with repeated quantitative sensory testing of A-delta and C-fibre function using cold and warm stimuli was used to assess which nerve fibre population that contributes to pain at perception threshold level using 1 s (vF1) and 10 s (vF10) von Frey filament stimulation of the skin. Results The main outcome was the finding that elevation of vF1 and vF10 occurred simultaneously and significantly prior to an increase in the perception level to cold or warmth during the continuous nerve block. Single patients demonstrated a slight decrease in cold perception levels at the time of elevation of vF1 or vF10 and a possible contribution to mechanical allodynia from A-delta-fibres can therefore not completely be ruled out although the recorded alterations were minor. None of the patients reported an elevation of the perception level to warmth at the time of elevation of vF1 or vF10 excluding contribution from C-fibres. Further, only patients with clinically established SMA ( n = 9) reported continuous pain to a sustained 10 s von Frey filament stimulation (vF10). Patients with only DMA ( n = 9) reported pain merely for the initial 1–3 s of the total stimulus duration of 10 s and for a few seconds after the filament was lifted from the skin. Conclusions These findings support the role of A-beta fibres as peripheral mediators of both vF1 and vF10 although different receptor organs may be involved, i.e., rapidly (RA) and slowly (SA-I) adapting mechanoreceptors. Implications Techniques to quantify the different allodynias at perception threshold level deserve further attention as possible adjuncts to suprathreshold stimuli in intervention studies aimed at modifying these stimulus-evoked phenomena.

Muscle Receptor Organs in the Crayfish Abdomen: A Student Laboratory Exercise in Proprioception

The primary purpose of this experiment is to demonstrate primary sensory neurons conveying information of joint movements and positions as proprioceptive information for an animal. An additional objective of this experiment is to learn anatomy of the preparation by staining, dissection and viewing of neurons and sensory structures under a dissecting microscope. This is performed by using basic neurophysiological equipment to record the electrical activity from a joint receptor organ and staining techniques. The muscle receptor organ (MRO) system in the crayfish is analogous to the intrafusal muscle spindle in mammals, which aids in serving as a comparative model that is more readily accessible for electrophysiological recordings. In addition, these are identifiable sensory neurons among preparations. The preparation is viable in a minimal saline for hours which is amenable for student laboratory exercises. The MRO is also susceptible to neuromodulation which encourages intriguing questions in the sites of modulatory action and integration of dynamic signals of movements and static position along with a gain that can be changed in the system.

Muscle Receptor Organs in the Crayfish Abdomen: A Student Laboratory Exercise in Proprioception

The primary purpose of this experiment is to demonstrate primary sensory neurons conveying information of joint movements and positions as proprioceptive information for an animal. An additional objective of this experiment is to learn anatomy of the preparation by staining, dissection and viewing of neurons and sensory structures under a dissecting microscope. This is performed by using basic neurophysiological equipment to record the electrical activity from a joint receptor organ and staining techniques. The muscle receptor organ (MRO) system in the crayfish is analogous to the intrafusal muscle spindle in mammals, which aids in serving as a comparative model that is more readily accessible for electrophysiological recordings. In addition, these are identifiable sensory neurons among preparations. The preparation is viable in a minimal saline for hours which is amenable for student laboratory exercises. The MRO is also susceptible to neuromodulation which encourages intriguing questions in the sites of modulatory action and integration of dynamic signals of movements and static position along with a gain that can be changed in the system.

Mechanisms of Sound Localization in Mammals

The ability to determine the location of a sound source is fundamental to hearing. However, auditory space is not represented in any systematic manner on the basilar membrane of the cochlea, the sensory surface of the receptor organ for hearing. Understanding the means by which sensitivity to spatial cues is computed in central neurons can therefore contribute to our understanding of the basic nature of complex neural representations. We review recent evidence concerning the nature of the neural representation of auditory space in the mammalian brain and elaborate on recent advances in the understanding of mammalian subcortical processing of auditory spatial cues that challenge the "textbook" version of sound localization, in particular brain mechanisms contributing to binaural hearing.

Severe and extensive neonatal hearing loss in cats results in auditory cortex plasticity that differentiates into two regions

We examined the response characteristics of primary auditory cortex (A1) neurons in adult cats partially but extensively deafened by ototoxic drugs 2-8 days after birth. The damage evoked extensive A1 topographic map reorganization as also found by others, but a novel finding was that in the majority of cats with low-frequency edges to the cochlear lesion, the area of reorganization segregated into two areas expressing the same novel frequency inputs but differentiated by neuronal sensitivity and responsiveness. Immediately adjacent to normal A1 is an approximately 1.2-mm-wide area of reorganization in which sensitivity and responsiveness to sound are similar to that in normal A1 in the same animals and in unlesioned adult animals. Extending further into deprived A1 is a more extensive area of reorganization where neurons have poorer sensitivity and responsiveness to new inputs. These two areas did not differ in response-area bandwidth and response latency. We interpret these novel changes as the cortical consequences of severe receptor organ lesions extending to low-frequency cochlear regions. We speculate that the two areas of A1 reorganization may reflect differences in the transcortical spatial distribution of thalamo-cortical and horizontal intracortical connections. Qualitatively similar changes in response properties have been seen after retinal lesions producing large areas of visual cortical reorganization, suggesting they might be a general consequence of receptor lesions that deprive large regions of cortex of normal input. These effects may have perceptual implications for the use of cochlear implants in patients with residual low-frequency hearing.

Dummies versus Air Puffs: Efficient Stimulus Delivery for Low-Volatile Odors

Aiming to unravel how animals perceive odors, a variety of neurophysiological techniques are used today. For olfactory stimulation, odors are commonly incorporated into a constant airstream that carries odor molecules to the receptor organ (air-delivered stimulation). Such odor delivery works well for odors of high volatility (naturally effective over long distances) but less or not at all for low-volatile odors (usually only received at short range). We developed a new odor stimulation technique especially suited for low-volatile odors and compared it with conventional air-delivered stimulation using 2 neurophysiological approaches. Odor-loaded dummies were moved into close vicinity of the receptor organs on the antenna of the Florida carpenter ant Camponotus floridanus (dummy-delivered stimulation). Neuronal activity was monitored either at receptor neuron level using electroantennography or in the first olfactory neuropile, the antennal lobes, using calcium imaging. We tested 3 odors of different volatility: C. floridanus' highly volatile alarm pheromone undecane, its low-volatile trail pheromone nerolic acid, and an even less volatile, behaviorally active C23 alkene, cis-9-tricosene. For low-volatile odors, dummy-delivered stimulation was particularly efficient. We conclude that dummy-delivered stimulation is advantageous compared to the commonly used air-delivered stimulation when studying an animal's detection and processing of low-volatile odors.

Expression Analysis of the 3 G-Protein Subunits, Gα, Gβ, and Gγ, in the Olfactory Receptor Organs of Adult Drosophila melanogaster

In many species, olfactory transduction is triggered by odorant molecules that interact with olfactory receptors coupled to heterotrimeric G-proteins. The role of G-protein-linked transduction in the olfaction of Drosophila is currently under study. Here, we supply a thorough description of the expression in the olfactory receptor organs (antennae and maxillary palps) of all known Drosophila melanogaster genes that encode for G-proteins. Using RT-polymerase chain reaction, we analyzed 6 Galpha (G(s), G(i), G(q), G(o), G(f), and concertina), 3 Gbeta (G(beta5), G(beta13F), and G(beta76C)), and 2 Ggamma genes (G(gamma1) and G(gamma30A)). We found that all Galpha protein-encoding genes showed expression in both olfactory organs, but G(f) mRNA was not detected in palps. Moreover, all the Gbeta and Ggamma genes are expressed in antennae and palps, except for G(beta76C). To gain insight into the hypothesis of different G-protein subunits mediating differential signaling in olfactory receptor neurons (ORNs), we performed immunohistochemical studies to observe the expression of several Galpha and Gbeta proteins. We found that Gs, Gi, Gq, and G(beta13F) subunits displayed generalized expression in the antennal tissue, including ORNs support cells and glial cells. Finally, complete coexpression was found between Gi and Gq, which are mediators of the cyclic adenosine monophosphate and IP3 transduction cascades, respectively.

SA-I Mechanoreceptor Position in Fingertip Skin May Impact Sensitivity to Edge Stimuli

Background:The skin plays a role in conditioning mechanical indentation into distributions of stress/strain that mechanoreceptors convert into neural signals. Solid mechanics methods have modelled the skin to predict the in vivo neural response from mechanoreceptors. Despite their promise, current models cannot explain the role that anatomical positioning and receptor organ morphology play in producing differences in neural response. This work hypothesises that the skin's intermediate ridges may help explain, in part, the sensitivity of slowly adapting type I (SA-I) mechanoreceptors to edge stimuli.Method:Two finite-element models of the fingertip were built, validated and used to analyse the functionality of the intermediate ridges. One of the two-dimensional, cross-sectional models included intermediate ridges, while the other did not. The analysis sought to determine if intermediate ridges (1) increase the magnitude of strain energy density (SED) near the SA-I location and (2) help differentiate one 2.0-mm indenter from two 0.5-mm wide indenters with a 1.0-mm gap.Results:Higher concentrations of SED were found near the tips of the intermediate ridges, the anatomical location that coincides with the SA-I receptors. This first result suggested that the location of the SA-Is in the stiffer epidermal tissue helps magnify their response to edge stimuli. The second result was that both models were equally capable of predicting the spatial structure within the in vivo neural responses, and therefore the addition of intermediate ridges did not help in differentiating the indenters.Conclusion:The finding, a 15%–35% increase in response when the sampling point lies within the stiffer tissue at the same depth, seeks to inform the positioning of force sensors in robotic skin substrates.

Choline acetyltransferase and NADPH-diaphorase activity in the nervous system and receptor organs of nemerteans

Choline acetyltransferase and NADPH-diaphorase activity in the nervous system and receptor organs of nemerteans

Morphologic Indication for Proprioception in the Human Ciliary Muscle

To search for proprioceptive nerve terminals in human ciliary muscle. In 48 human donor eyes, histologic and ultrathin sections cut in different planes and wholemounts of the ciliary muscle were studied. Immunohistochemical staining with antibodies against pan-neuronal antigens and antigens reported as markers for sensory terminals in other organs was performed. Among the markers for proprioceptive terminals, only calretinin was present in the ciliary body. Calretinin-immunoreactive (IR) nerve terminals surrounded the posterior and reticular ciliary muscle tips and their elastic tendons. Terminals in that region contained mitochondria and neurofilaments. At the anterior tips larger terminals with numerous membrane-filled vesicles were located between the muscle fibers. The most elaborate network of calretinin-IR nerve fibers was present in the ground plate covering the circular muscle portion. Here calretinin-IR neurons with morphologic features of mechanoreception were present. Within the circular muscle portion numerous calretinin-IR ganglion cells were found. Their processes were connected to the calretinin-IR network but also surrounded ciliary muscle cells and NADPH-diaphorase-positive ganglion cells. These morphologic findings indicate that there are proprioreceptors in the ciliary muscle that morphologically and presumably functionally differ at different locations. At the posterior muscle tips, the receptors could measure stretch of the tendons, whereas the large receptor organs located at the anterior muscle tips morphologically resemble mechanoreceptors measuring shear stress. The presence of the numerous intrinsic nerve cells indicates that contraction of the circular muscle portion can be modulated locally via a self-contained reflex arc.

Investigation of β2‐adrenoceptor subtype selectivity and organ specificity for bedoradrine (KUR‐1246), a novel tocolytic beta‐adrenergic receptor stimulant

The aim of this study was to evaluate the beta-adrenergic receptor (beta-AR) selectivity, organ specificity and efficacy of delaying the onset of spontaneous delivery of bedoradrine (KUR-1246), a novel uterine relaxant. beta-AR selectivity was evaluated in terms of the amount of cyclic adenosine monophosphate produced by bedoradrine, ritodrine and isoprenaline in Chinese hamster ovary cells expressing human beta(1)-, beta(2)-AR or beta(3)-AR. Inhibition of contractions of the atrium, trachea and proximal colon by bedoradrine were compared with those of the uterus in pregnant rats using an organ bath method. Finally, the delaying effect of bedoradrine on spontaneous labor was evaluated by an in vivo study using term pregnant rats. EC(50) values of bedoradrine for cyclic adenosine monophosphate production in Chinese hamster ovary cells via beta(1)-, beta(2)- and beta(3)-AR were 2400 +/- 30, 2.9 +/- 0.10 and 363 +/- 3 nmol/L, respectively, indicating that bedoradrine had 832- and 126-fold higher selectivity for beta(2)-AR than for beta(1)- and beta(3)-AR. EC(50) values of bedoradrine for the uterus, atrium, trachea and proximal colon were 1.01 +/- 0.27, 2300 +/- 356, 1610 +/- 299 and 219 +/- 23.5 nmol/L, respectively. Thus, bedoradrine was 2280-, 1590- and 217-fold more specific for the uterus than for the atrium, trachea and proximal colon, respectively. Bedoradrine delayed the spontaneous delivery of 21-day-pregnant rats in a dose-dependent manner. Bedoradrine is a promising drug for the treatment of preterm labor in obstetrical practice because it has better selectivity for beta(2)-AR and specificity for the uterus than currently used agents and may effectively delay spontaneous delivery.

Cochlear Labyrinth Volume and Hearing Abilities in Primates

The primate cochlea is a membranous, fluid-filled receptor organ that is specialized for sound detection. Like other parts of the inner ear, the cochlea is contained within the bony labyrinth of the petrous temporal bone. The close anatomical relationship between the bony cochlear labyrinth and the membranous cochlea provides an opportunity to quantify cochlear size using osteological specimens. Although mechanisms of cochlear frequency analysis are well studied, relatively little is known about the functional consequences of interspecific variation in cochlear size. Previous comparative analyses have linked increases in basilar membrane length to decreases in both the high and low frequency limits of hearing in mammals. However, these analyses did not consider the potentially confounding effects of body mass or phylogeny. Here, we present measurements of cochlear labyrinth volume in 33 primate species based on high-resolution computed tomography. These data demonstrate that cochlear labyrinth volume is strongly negatively allometric with respect to body mass. Scaling of cochlear volume in primates is very similar to scaling of basilar membrane length among mammals generally. Furthermore, an analysis of 10 primate taxa with published audiograms reveals that cochlear labyrinth volume is significantly negatively correlated with the high frequency limit of hearing. This result is independent of body mass and phylogeny, suggesting that cochlear size is functionally related to the range of audible frequencies in primates. Although the nature of this functional relationship remains speculative, our findings suggest that some hearing parameters of extinct taxa may be estimated using fossil petrosals.

Movement encoding by a stretch receptor in the soft-bodied caterpillar,Manduca sexta

In a wide variety of animals, stretch receptors provide proprioceptive feedback for motion control. However, for animals that lack a stiff skeleton, it is unclear what information is being detected and how this is incorporated into behavior. Because such animals can change their body shape from moment-to-moment, information about body configuration could be particularly important for coordination. This study uses larval stage Lepidoptera (Manduca sexta) to examine how the longitudinal stretch receptor organ (SRO) responds to behaviorally appropriate movements. We characterized the responses of the SRO to changes in strain using magnitudes and velocities matching those seen physiologically. We found that the SRO response characteristics are compatible with the regulation of stance and with the defensive response to noxious stimuli. However, we also found that movements during crawling produce SRO responses that are dominated by the interdependence of phasic, tonic and slowly adaptive components. Ablation of stretch receptors in the proleg-bearing, fourth abdominal segment did not have any observable effect on behaviors, which suggests that the SROs are not essential for coordinating overt movements. We discuss the implications of these findings in the context of specific behaviors, and explore how the SRO response might be utilized during animal behavior.

The evolutionary origin of auditory receptors in Tettigonioidea: the complex tibial organ of Schizodactylidae

Audition in insects is of polyphyletic origin. Tympanal ears derived from proprioceptive or vibratory receptor organs, but many questions of the evolution of insect auditory systems are still open. Despite the rather typical bauplan of the insect body, e.g., with a fixed number of segments, tympanal ears evolved at very different places, but only ensiferans have ears at the foreleg tibia, located in the tibial organ. The homology and monophyly of ensiferan ears is controversial, and no precursor organ was unambiguously identified for auditory receptors. The latter can only be identified by comparative study of recent atympanate taxa. These atympanate taxa are poorly investigated. In this paper, we report the neuroanatomy of the tibial organ of Comicus calcaris (Irish 1986), an atympanate Schizodactylid (splay-footed cricket). This representative of a Gondwana relict group has a tripartite sensory organ, homologous to tettigoniid ears. A comparison with morphology-based cladistic phylogeny indicates that the tripartite neuronal organization present in the majority of Tettigonioidea presumably preceded evolution of a hearing sense in the Tettigonioidea. Furthermore, the absence of a tripartite organ in Grylloidea argues against a monophyletic origin and homology of the cricket and katydid ears. The tracheal attachment of sensory neurons typical for ears of Tettigonioidea is present in C. calcaris and may have facilitated cooption for auditory function. The functional auditory organ was presumably formed in evolution by successive non-neural modifications of trachea and tympana. This first investigation of the neuroanatomy of Schizodactylidae suggests a non-auditory chordotonal organ as the precursor for auditory receptors of related tympanate taxa and adds evidence for the phylogenetic position of the group.

Distribution, density and morphology of electroreceptor organs in mormyrid weakly electric fish: anatomical investigations of a receptor mosaic

Abstract Gnathonemus petersii and other African weakly electric fish (Mormyridae) produce electric signals in order to sense their environment, a process called active electrolocation. During active electrolocation electrical images of objects in the environment are cast onto a mosaic of electroreceptors, which are embedded in the animal's skin. In Gn. petersii and four other species of mormyrid fish, the densities of electroreceptor organs (mormyromasts and ampullary organs) were determined at various skin regions, including the chin, the nasal region and the back. In all species investigated, the highest mormyromast densities were found at the chin, followed by the nasal region. In addition to this comparative approach, we investigated the electroreceptive epidermis of Gn. petersii in more detail. At the moveable chin appendix, the Schnauzenorgan, scanning electron microscopy analysis helped to elucidate the mosaic‐like distribution and the morphology of the electroreceptor organs and their embedding in the epidermis. Because the number of mormyromasts increased very little when fish got bigger, receptor organ densities decreased with standard length. Mormyromast density at the Schnauzenorgan, especially at its tip, highly exceeded that at all other skin regions. Along the Schnauzenorgan, receptor densities decreased exponentially from the tip towards the base. At the nasal region, mormyromast densities were more than three times higher compared to the rest of the fish's head and trunk. A similar distribution to that of the mormyromasts was found for the ampullary electroreceptor organs, which are used for passive electroreception. Our findings support the hypothesis that at least in Gn. petersii the Schnauzenorgan and the nasal region are electroreceptive foveae.

Functional foveae in an electrosensory system

Several species of Mormyrid weakly electric fish have a mobile chin protuberance that serves as a mobile antenna during prey detection, tracking behaviors, and foraging for food. It has been proposed that it constitutes a fovea of the electrosensory system. The distribution of the three types of receptor organs involved in active imaging of the local surroundings, prey detection, and passive electroreception, and their central projection to the electrosensory lobe (ELL), have been studied in Gnathonemus petersii. Density distributions were compared for different body regions. Primary afferent projections were labeled with biocytin or biotinylated dextrans. This showed that there is considerable central "over-representation" of the mandibular and nasal regions of the sensory surface involved in electrolocation, at the expense of the other body regions investigated. This over-representation is not a mere effect of the very high density of receptor organs in these areas, but is found to be due to central magnification. This magnification differs between the subclasses of electroreceptors, suggesting a functional segregation in the brain. We conclude that the chin protuberance and the nasal region are the regions of greatest sensitivity for the resistive, capacitive, and low-frequency characteristics of the environment, and are probably most important in prey detection, whereas other regions of the skin with a lesser resolution and sensitivity to phase distortion of the EOD, in particular the trunk, are probably designed for imaging larger, inanimate features of the environment. Our data support the hypothesis that the chin appendage and nasal region are functionally distinct electrosensory foveae.

Osteopontin is not Critical for Otoconia Formation or Balance Function

Unlike the structural and mechanical role of bone crystals, the inertial mass of otoconia crystals provides a shearing force to stimulate the mechanoreceptors of the utricle and saccule (the gravity receptor organ) under the stimuli of linear motion. It is not clear whether otoconia, composed primarily of CaCO3 and glycoproteins, go through similar calcification processes as bone. We have recently shown that otoconin-90 (Oc90) regulates the growth of otoconia crystals as osteopontin does bone crystals. Here, we analyzed the role of this non-collagenous bone matrix protein, osteopontin, in otoconia formation and balance function utilizing its knockout mice, whose inner ear phenotype has not been examined. Despite the presence of the protein in wild-type otoconia and vestibular hair cells, morphological, ultrastructural, and protein and calcium composition analyses of osteopontin null otoconia show that the protein is not needed for crystal formation, and no evidence of compensatory protein deposition is found. Employment of a wide spectrum of balance behavioral tests demonstrates that the protein is not critical for balance function either, which is confirmed by the normal function of the gravity receptor organ directly measured with linear vestibular-evoked potentials (VsEPs). When compared with findings on other otoconins, the data manifest a hierarchy of importance of proteins in crystallization and indicate mechanistic similarities and differences between bone and otoconia calcification.

Otoconin-90 deletion leads to imbalance but normal hearing: A comparison with other otoconia mutants

Our sense of gravitation and linear acceleration is mediated by stimulation of vestibular hair cells through displacement of otoconia in the utricle and saccule (the gravity receptor organ). We recently showed that otoconin-90 (Oc90) deletion led to formation of giant otoconia. In the present study, we determined the extent to which the giant otoconia affected balance and gravity receptor sensory input and compared the findings with other otoconia mutants. We employed a wide spectrum of balance behavioral tests, including reaching and air-righting reflexes, gait, swimming, beam-crossing, rotorod latencies, and a direct measure of gravity receptor input, vestibular evoked potentials (VsEPs). All tests on homozygous adult mutants consistently ranked the order of imbalance as (from worst to best) Nox3 het<otopetrin 1 tlt<Oc90 null<Oc90 wild type and C57Bl/6 mice using systematic statistical comparisons of the frequency of occurrence or the severity of abnormal functions. This order coincides with the degree of otoconia deficiencies and is consistent with VsEP measures. Notably, all mice (except Nox3 het) showed remarkable learned adaptation to peripheral vestibular deficits by staying on the rotating rod significantly longer in each successive trial, and the rate and extent of such learned improvements ranked the same order as their initial balance ability. Despite the vestibular morbidity, Oc90 null mice had normal hearing, as measured by auditory brainstem responses (ABRs) and distortion products of otoacoustic emissions (DPOAEs). The study demonstrates that the remnant otoconia mass in Oc90 nulls does stimulate the gravity receptor organs, which was likely responsible for the improved balance performance relative to strains with absent otoconia. Furthermore, the combination of direct electrophysiological measures and a series of behavioral tests can be used to interpret the imbalance severity arising from altered inputs from the gravity receptor end organ.