The efferent pathway strengthens the auditory system for optimal performance by fine-tuning the response and protecting the inner ear from noise-induced damage. Although it has been well documented that efference helps defend against hair cell and synaptic extinction, the mechanisms of its otoprotective role have still not been established. Specifically, the effect of efference on an individual hair cell's recovery from mechanical overstimulation has not been demonstrated. In the current work, we explored the impact of efferent stimulation on this recovery using in vitro preparations of hair cells situated in the sacculi of American bullfrogs (Rana catesbeiana). In the absence of efferent stimulus, exposure of a hair bundle to high-amplitude mechanical deflection detuned it from its oscillatory regime, with the extent of detuning dependent on the applied signal. Efferent actuation concomitant with the hair bundle's relaxation from a high-amplitude deflection notably changed the recovery profile and often entirely eliminated the transition to quiescence. Our findings indicate that the efferent system acts as a control mechanism that determines the dynamic regime in which the hair cell is poised.

Meniere disease (MD) is a rare disorder of the inner ear defined by sensorineural hearing loss (SNHL) associated with episodes of vertigo and tinnitus. The phenotype is variable, and it may be associated with other comorbidities such as migraine, respiratory allergies, and several autoimmune disorders. The condition has a significant heritability according to epidemiological and familial segregation studies. Familial MD is found in 10% of cases, the most frequently found genes being OTOG, MYO7A, and TECTA, previously associated with autosomal dominant and recessive non-syndromic SNHL. These findings suggest a new hypothesis where proteins involved in the extracellular structures in the apical surface of sensory epithelia (otolithic and tectorial membranes) and proteins in the stereocilia links would be key elements in the pathophysiology of MD. The ionic homeostasis of the otolithic and tectorial membranes could be critical to suppress the innate motility of individual hair cell bundles. Initially, focal detachment of these extracellular membranes may cause random depolarization of hair cells and will explain changes in tinnitus loudness or trigger vertigo attacks in early stages of MD. With the progression of the disease, a larger detachment will lead to an otolithic membrane herniation into the horizontal semicircular canal with dissociation in caloric and head impulse responses. Familial MD shows different types of inheritance, including autosomal dominant and compound recessive patterns and implementation of genetic testing will improve our understanding of the genetic structure of MD.

The benign paroxysmal positional vertigo (BPPV) is a vestibular disorder cause of vertigo. The BPPV may be corrected mechanically by repositioning maneuvers but even after successful maneuvers, some patients report residual dizziness for a certain period afterward. Early recognition and treatment might decrease the incidence of residual dizziness in patients with BPPV, especially in those patients with psychiatric comorbidities and in the elderly, lowering the risk of falling. Many pathogenetic hypotheses for residual dizziness are under debate. The purpose of this review was to identify, evaluate and review recent researches about possible causal factors involved in residual dizziness and the implications on clinical practice. A literature search was performed using different databases such as Pubmed and Scopus. The following search terms were used: residual dizziness, otolithic membrane and BPPV. The search found a total of 1192 titles, which were reduced to 963 after a procedure of de-duplication of the found titles. The research was then restricted to an interval of time comprised between 2000 and 2016 for a total of 800 titles. Among these titles, only those including the terms benign paroxysmal positional vertigo were considered eligible for this review. Only publications in English language were taken into consideration and we excluded those with not available abstract. Finally, 90 abstracts were obtained and critically evaluated by two different Authors, and additional studies were identified by hand searching from the references of artiche of interest. Only 53 were included in this work.

The cupula is a gelatinous membrane overlying the crista ampullaris of the semicircular canal, important for sensing rotation of the head and critical for normal balance. Recently the zona pellucida like domain containing 1 protein (ZPLD1, also known as cupulin) was identified in the cupula of fish. Here, we describe two new spontaneous mutations in the mouse Zpld1 gene, which were discovered by the circling behavior of mutant mice, an indicator of balance dysfunction. The Zpld1 mutant mice exhibited normal hearing function as assessed by auditory brainstem response (ABR) measurements, and their otolithic organs appeared normal. In the inner ear, Zpld1 mRNA expression was detected only in the hair cells and supporting cells of the crista ampullaris. Normal vestibular sensory evoked potential (VsEP) responses and abnormal vestibulo-ocular reflex (VOR) responses demonstrated that the vestibular dysfunction of the Zpld1 mutant mice is caused by loss of sensory input for rotary head movements (detected by cristae ampullaris) and not by loss of input for linear head translations (detected by maculae of the utricle and saccule). Taken together, these results are consistent with ZPLD1 being an important functional component of the cupula, but not tectorial or otoconial membranes.

Deflecting biomineralized crystals attached to vestibular hair cells are necessary for maintaining balance. Zebrafish (Danio rerio) are useful organisms to study these biomineralized crystals called otoliths, as many required genes are homologous to human otoconial development. We sought to identify and characterize the causative gene in a trio of homozygous recessive mutants, no content (nco) and corkscrew (csr), and vanished (vns), which fail to develop otoliths during early ear development. We show that nco, csr, and vns have potentially deleterious mutations in polyketide synthase (pks1), a multi-modular protein that has been previously implicated in biomineralization events in chordates and echinoderms. We found that Otoconin-90 (Oc90) expression within the otocyst is diffuse in nco and csr; therefore, it is not sufficient for otolith biomineralization in zebrafish. Similarly, normal localization of Otogelin, a protein required for otolith tethering in the otolithic membrane, is not sufficient for Oc90 attachment. Furthermore, eNOS signaling and Endothelin-1 signaling were the most up- and down-regulated pathways during otolith agenesis in nco, respectively. Our results demonstrate distinct processes for otolith nucleation and biomineralization in vertebrates and will be a starting point for models that are independent of Oc90-mediated seeding. This study will serve as a basis for investigating the role of eNOS signaling and Endothelin-1 signaling during otolith formation.