- Re: The prostatic utricle: an under-recognized condition resulting in significant morbidity in boys with both hypospadias and normal external genitalia. [Letter]
- JPJ Pediatr Urol 2019 Apr 26
- cVEMP correlated with imbalance in a mouse model of vestibular disorder. [Journal Article]
- EHEnviron Health Prev Med 2019 Jun 01; 24(1):39
- CONCLUSIONS: This study demonstrated impaired cVEMP and correlations of cVEMP with imbalance determined by behavior tests in a mouse model of vestibular disorder.
- Spontaneous and Acetylcholine Evoked Calcium Transients in the Developing Mouse Utricle. [Journal Article]
- FCFront Cell Neurosci 2019; 13:186
- Spontaneous calcium transients are present during early postnatal development in the mouse retina and cochlea, and play an important role in maturation of the sensory organs and neural circuits in th…
Spontaneous calcium transients are present during early postnatal development in the mouse retina and cochlea, and play an important role in maturation of the sensory organs and neural circuits in the central nervous system (CNS). It is not known whether similar calcium transients occur during postnatal development in the vestibular sensory organs. Here we demonstrate spontaneous intracellular calcium transients in sensory hair cells (HCs) and supporting cells (SCs) in the murine utricular macula during the first two postnatal weeks. Calcium transients were monitored using a genetically encoded calcium indicator, GCaMP5G (G5), at 100 ms-frame-1 in excised utricle sensory epithelia, including HCs, SCs, and neurons. The reporter line expressed G5 and tdTomato (tdT) in a Gad2-Cre dependent manner within a subset of utricular HCs, SCs and neurons. Kinetics of the G5 reporter limited temporal resolution to calcium events lasting longer than 200 ms. Spontaneous calcium transients lasting 1-2 s were observed in the expressing population of HCs at birth and slower spontaneous transients lasting 10-30 s appeared in SCs by P3. Beginning at P5, calcium transients could be modulated by application of the efferent neurotransmitter acetylcholine (ACh). In mature mice, calcium transients in the utricular macula occurred spontaneously, had a duration 1-2 s, and could be modulated by the exogenous application of acetylcholine (ACh) or muscarine. Long-lasting calcium transients evoked by ACh in mature mice were blocked by atropine, consistent with previous reports describing the role of muscarinic receptors expressed in calyx bearing afferents in efferent control of vestibular sensation. Large spontaneous and ACh evoked transients were reversibly blocked by the inositol trisphosphate receptor (IP3R) antagonist aminoethoxydiphenyl borate (2-APB). Results demonstrate long-lasting calcium transients are present in the utricular macula during the first postnatal week, and that responses to ACh mature over this same time period.
- Growth and cellular patterning during fetal human inner ear development studied by a correlative imaging approach. [Journal Article]
- BDBMC Dev Biol 2019 May 20; 19(1):11
- CONCLUSIONS: We present structural information on human inner ear development across multiple levels of biological organization, including gross-morphology of the inner ear, cellular and subcellular details of hearing and vestibular organs, as well as ultrastructural details in the developing sensory epithelia. This enabled the gathering of detailed information regarding morphometric changes as well in realizing the complex developmental patterns of the human inner ear. We were able to quantify the volumetric and linear aspects of selected gestational inner ear specimens enabling a better understanding of the cellular changes across the fetal gestational timeline. Moreover, these data could serve as a reference for better understanding disorders that arise during inner ear development.
- Otopetrin-2 Immunolocalization in the Human Macula Utricle. [Journal Article]
- AOAnn Otol Rhinol Laryngol 2019; 128(6_suppl):96S-102S
- CONCLUSIONS: Otopetrin-2 was localized in supporting cells in a similar fashion that otopetrin-1 previously reported in the mouse macula utricle. The differential expression of otopetrin-2 in the supporting cells of the human macula utricle suggest an important role in the vestibular sensory periphery homeostasis and otolith maintenance.
- On the Legacy of Genetically Altered Mouse Models to Explore Vestibular Function: Distribution of Vestibular Hair Cell Phenotypes in the Otoferlin-Null Mouse. [Journal Article]
- AOAnn Otol Rhinol Laryngol 2019; 128(6_suppl):125S-133S
- CONCLUSIONS: These findings support the notion that modifications resulting in a specific component of vestibular hypofunction are not accompanied by widespread morphologic and cellular changes in the vestibular sensory epithelia.
- Ultrastructural Characterization of Stem Cell-Derived Replacement Vestibular Hair Cells Within Ototoxin-Damaged Rat Utricle Explants. [Journal Article]
- ARAnat Rec (Hoboken) 2019 May 14
- The auditory apparatus of the inner ear does not show turnover of sensory hair cells (HCs) in adult mammals; in contrast, there are many observations supporting low-level turnover of vestibular HCs w…
The auditory apparatus of the inner ear does not show turnover of sensory hair cells (HCs) in adult mammals; in contrast, there are many observations supporting low-level turnover of vestibular HCs within the balance organs of mammalian inner ears. This low-level renewal of vestibular HCs exists during normal conditions and it is further enhanced after trauma-induced loss of these HCs. The main process for renewal of HCs within mammalian vestibular epithelia is a conversion/transdifferentiation of existing supporting cells (SCs) into replacement HCs.In earlier studies using long-term organ cultures of postnatal rat macula utriculi, HC loss induced by gentamicin resulted in an initial substantial decline in HC density followed by a significant increase in the proportion of HCs to SCs indicating the production of replacement HCs. In the present study, using the same model of ototoxic damage to study renewal of vestibular HCs, we focus on the ultrastructural characteristics of SCs undergoing transdifferentiation into new HCs. Our objective was to search for morphological signs of SC plasticity during this process. In the utricular epithelia, we observed immature HCs, which appear to be SCs transdifferentiating into HCs. These bridge SCs have unique morphological features characterized by formation of foot processes, basal accumulation of mitochondria, and an increased amount of connections with nearby SCs. No gap junctions were observed on these transitional cells. The tight junction seals were morphologically intact in both control and gentamicin-exposed explants. Anat Rec, 2019. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.
- Asymmetric cupula displacement due to endolymph vortex in the human semicircular canal. [Journal Article]
- BMBiomech Model Mechanobiol 2019 May 08
- The vestibular system in the inner ear senses angular head manoeuvres by endolymph fluid which deforms a gelatinous sensory structure (the cupula). We constructed computer models that include both th…
The vestibular system in the inner ear senses angular head manoeuvres by endolymph fluid which deforms a gelatinous sensory structure (the cupula). We constructed computer models that include both the endolymph flow (using CFD modelling), the cupula deformation (using FEM modelling), and the interaction between both (using fluid-structure interaction modelling). In the wide utricle, we observe an endolymph vortex. In the initial time steps, both the displacement of the cupula and its restorative forces are still small. As a result, the endolymph vortex causes the cupula to deform asymmetrically in an S-shape. The asymmetric deflection increases the cupula strain near the crista and, as a result, enhances the sensitivity of the vestibular system. Throughout the head manoeuvre, the maximal cupula strain is located at the centre of the crista. The hair cells at the crista centre supply irregularly spiking afferents, which are more sensitive than the afferents from the periphery. Hence, the location of the maximal strain at the crista may also increase the sensitivity of the semicircular canal, but this remains to be tested. The cupula overshoots its relaxed position in a simulation of the Dix-Hallpike head manoeuvre (3 s in total). A much faster head manoeuvre of 0.222 s showed to be too short to cause substantial cupula overshoot, because the cupula time scale of both models (estimated to be 3.3 s) is an order of magnitude larger than the duration of this manoeuvre.
- A review of mechanical and synaptic processes in otolith transduction of sound and vibration for clinical VEMP testing. [Journal Article]
- JNJ Neurophysiol 2019 May 01
- Older studies of mammalian otolith physiology have focused mainly on sustained responses to low-frequency (<50Hz) or maintained linear acceleration. So the otoliths have been regarded as acceleromete…
Older studies of mammalian otolith physiology have focused mainly on sustained responses to low-frequency (<50Hz) or maintained linear acceleration. So the otoliths have been regarded as accelerometers. Thus evidence of otolithic activation and high precision phase locking to high-frequency sound and vibration appears to be very unusual. However those results are exactly in accord with a substantial body of knowledge of otolith function in fish and frogs. It is likely that phase locking of otolith afferents to vibration is a general property of all vertebrates. This review examines the literature about the activation and phase locking of single otolithic neurons to air-conducted sound (ACS) and bone-conducted vibration (BCV), in particular the high precision of phase locking shown by mammalian irregular afferents which synapse on striolar type I hair cells by calyx endings. Potassium in the synaptic cleft between the type I hair cell receptor and the calyx afferent ending may be responsible for the tight phase locking of these afferents even at very high discharge rates. Since frogs and fish do not possess full calyx endings, it is unlikely that they show phase locking with such high precision and to such high frequencies as has been found in mammals. The high-frequency responses have been modelled as the otoliths operating in a seismometer mode rather than an accelerometer mode. These high-frequency otolithic responses constitute the neural basis for clinical vestibular-evoked myogenic potential (VEMP) tests of otolith function.
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- Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1. [Journal Article]
- EElife 2019 Apr 29; 8
- The mammalian cochlea loses its ability to regenerate new hair cells prior to the onset of hearing. In contrast, the adult vestibular system can produce new hair cells in response to damage, or by re…
The mammalian cochlea loses its ability to regenerate new hair cells prior to the onset of hearing. In contrast, the adult vestibular system can produce new hair cells in response to damage, or by reprogramming of supporting cells with the hair cell transcription factor Atoh1. We used RNA-seq and ATAC-seq to probe the transcriptional and epigenetic responses of utricle supporting cells to damage and Atoh1 transduction. We show that the regenerative response of the utricle correlates with a more accessible chromatin structure in utricle supporting cells compared to their cochlear counterparts. We also provide evidence that Atoh1 transduction of supporting cells is able to promote increased transcriptional accessibility of some hair cell genes. Our study offers a possible explanation for regenerative differences between sensory organs of the inner ear, but shows that additional factors to Atoh1 may be required for optimal reprogramming of hair cell fate.