The upregulation of K and HCN channels in developing spiral ganglion neurons is mediated by cochlear inner hair cells.

Spiral ganglion neurons (SGNs) are primary sensory afferent neurons that relay acoustic information from the cochlear inner hair cells (IHCs) to the brainstem. The response properties of different SGNs diverge to represent a wide range of sound intensities in an action-potential code. This biophysical heterogeneity is established during pre-hearing stages of development, a time when IHCs fire spontaneous Ca action potentials that drive glutamate release from their ribbon synapses onto the SGN terminals.

An Open-Source Deep Learning-Based GUI Toolbox For Automated Auditory Brainstem Response Analyses (ABRA).

In this paper, we introduce a new, open-source software developed in Python for analyzing Auditory Brainstem Response (ABR) waveforms. ABRs are a far-field recording of synchronous neural activity generated by the auditory fibers in the ear in response to sound, and used to study acoustic neural information traveling along the ascending auditory pathway. Common ABR data analysis practices are subject to human interpretation and are labor-intensive, requiring manual annotations and visual estimation of hearing thresholds.

Absence of Embigin accelerates hearing loss and causes sub-viability, brain and heart defects in C57BL/6N mice due to interaction with .

Mouse studies continue to help elaborate upon the genetic landscape of mammalian disease and the underlying molecular mechanisms. Here, we have investigated an allele maintained on a standard C57BL/6N background and on a co-isogenic C57BL/6N background in which the allele has been "repaired." The hypomorphic allele is present in several commonly used inbred mouse strains, predisposing them to progressive hearing loss, starting in high-frequency regions.

Age-related changes in P2Y receptor signalling in mouse cochlear supporting cells.

Our sense of hearing depends on the function of a specialised class of sensory cells, the hair cells, which are found in the organ of Corti of the mammalian cochlea. The unique physiological environment in which these cells operate is maintained by a syncitium of non-sensory supporting cells, which are crucial for regulating cochlear physiology and metabolic homeostasis. Despite their importance for cochlear function, the role of these supporting cells in age-related hearing loss, the most common sensory deficit in the elderly, is poorly understood.

Oncomodulin regulates spontaneous calcium signalling and maturation of afferent innervation in cochlear outer hair cells.

Cochlear outer hair cells (OHCs) are responsible for the exquisite frequency selectivity and sensitivity of mammalian hearing. During development, the maturation of OHC afferent connectivity is refined by coordinated spontaneous Ca activity in both sensory and non-sensory cells. Calcium signalling in neonatal OHCs can be modulated by oncomodulin (OCM, β-parvalbumin), an EF-hand calcium-binding protein.

Oncomodulin Regulates Spontaneous Calcium Signaling and Maturation of Afferent Innervation in Cochlear Outer Hair Cells.

Cochlear outer hair cells (OHCs) are responsible for the exquisite frequency selectivity and sensitivity of mammalian hearing. During development, the maturation of OHC afferent connectivity is refined by coordinated spontaneous Ca activity in both sensory and non-sensory cells. Calcium signaling in neonatal OHCs can be modulated by Oncomodulin (OCM, β-parvalbumin), an EF-hand calcium-binding protein.

A critical period of prehearing spontaneous Ca spiking is required for hair-bundle maintenance in inner hair cells.

Sensory-independent Ca spiking regulates the development of mammalian sensory systems. In the immature cochlea, inner hair cells (IHCs) fire spontaneous Ca action potentials (APs) that are generated either intrinsically or by intercellular Ca waves in the nonsensory cells. The extent to which either or both of these Ca signalling mechansims are required for IHC maturation is unknown.

AAV-mediated rescue of expression restores hair-cell function in a mouse model of recessive deafness.

The transduction of acoustic information by hair cells depends upon mechanosensitive stereociliary bundles that project from their apical surface. Mutations or absence of the stereociliary protein EPS8 cause deafness in humans and mice, respectively. knockout mice ( ) have hair cells with immature stereocilia and fail to become sensory receptors.

Signal transmission in mature mammalian vestibular hair cells.

The maintenance of balance and gaze relies on the faithful and rapid signaling of head movements to the brain. In mammals, vestibular organs contain two types of sensory hair cells, type-I and type-II, which convert the head motion-induced movement of their hair bundles into a graded receptor potential that drives action potential activity in their afferent fibers. While signal transmission in both hair cell types involves Ca-dependent quantal release of glutamate at ribbon synapses, type-I cells appear to also exhibit a non-quantal mechanism that is believed to increase transmission speed.

Oncomodulin (OCM) uniquely regulates calcium signaling in neonatal cochlear outer hair cells.

In cochlear outer hair cells (OHCs), a network of Ca channels, pumps and Ca-binding proteins (CaBPs) regulates the localization, spread, and magnitude of free Ca ions. During early postnatal development, OHCs express three prominent mobile EF-hand CaBPs: oncomodulin (OCM), α-parvalbumin (APV) and sorcin. We have previously shown that deletion of Ocm (Ocm) gives rise to progressive cochlear dysfunction in young adult mice.

Grxcr1 regulates hair bundle morphogenesis and is required for normal mechanoelectrical transduction in mouse cochlear hair cells.

Tasmanian devil (tde) mice are deaf and exhibit circling behaviour. Sensory hair cells of mutants show disorganised hair bundles with abnormally thin stereocilia. The origin of this mutation is the insertion of a transgene which disrupts expression of the Grxcr1 (glutaredoxin cysteine rich 1) gene.

Neuroplastin genetically interacts with Cadherin 23 and the encoded isoform Np55 is sufficient for cochlear hair cell function and hearing.

Mammalian hearing involves the mechanoelectrical transduction (MET) of sound-induced fluid waves in the cochlea. Essential to this process are the specialised sensory cochlear cells, the inner (IHCs) and outer hair cells (OHCs). While genetic hearing loss is highly heterogeneous, understanding the requirement of each gene will lead to a better understanding of the molecular basis of hearing and also to therapeutic opportunities for deafness.

Current Response in Ca 1.3 Mouse Vestibular and Cochlear Hair Cells.

Signal transmission by sensory auditory and vestibular hair cells relies upon Ca-dependent exocytosis of glutamate. The Ca current in mammalian inner ear hair cells is predominantly carried through Ca 1.3 voltage-gated Ca channels.

Sensory adaptation at ribbon synapses in the zebrafish lateral line.

Key Points: The present study aimed to determine the sensory adaptation characteristics of hair cell ribbon synapses in vivo. Hair cells of the zebrafish lateral line transmit hydrodynamic stimuli to the posterior lateral line ganglion afferent neurons. Excitatory hair bundle deflections by water-jet stimuli cause glutamate release at hair cell synapses with a rapid (phasic) and a sustained component, which are likely linked to the exocytosis of distinct vesicle pools.

MET currents and otoacoustic emissions from mice with a detached tectorial membrane indicate the extracellular matrix regulates Ca near stereocilia.

Key Points: The aim was to determine whether detachment of the tectorial membrane (TM) from the organ of Corti in Tecta/Tectb mice affects the biophysical properties of cochlear outer hair cells (OHCs). Tecta/Tectb mice have highly elevated hearing thresholds, but OHCs mature normally. Mechanoelectrical transducer (MET) channel resting open probability (P ) in mature OHC is ∼50% in endolymphatic [Ca ], resulting in a large standing depolarizing MET current that would allow OHCs to act optimally as electromotile cochlear amplifiers.

Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea.

Key Points: Age-related hearing loss is a progressive hearing loss involving environmental and genetic factors, leading to a decrease in hearing sensitivity, threshold and speech discrimination. We compared age-related changes in inner hair cells (IHCs) between four mouse strains with different levels of progressive hearing loss. The surface area of apical coil IHCs (9-12 kHz cochlear region) decreases by about 30-40% with age.

Loss of Baiap2l2 destabilizes the transducing stereocilia of cochlear hair cells and leads to deafness.

Key Points: Mechanoelectrical transduction at auditory hair cells requires highly specialized stereociliary bundles that project from their apical surface, forming a characteristic graded 'staircase' structure. The morphogenesis and maintenance of these stereociliary bundles is a tightly regulated process requiring the involvement of several actin-binding proteins, many of which are still unidentified. We identify a new stereociliary protein, the I-BAR protein BAIAP2L2, which localizes to the tips of the shorter transducing stereocilia in both inner and outer hair cells (IHCs and OHCs).

Pathophysiological changes in inner hair cell ribbon synapses in the ageing mammalian cochlea.

Key Points: Age-related hearing loss (ARHL) is associated with the loss of inner hair cell (IHC) ribbon synapses, lower hearing sensitivity and decreased ability to understand speech, especially in a noisy environment. Little is known about the age-related physiological and morphological changes that occur at ribbon synapses. We show that the differing degrees of ARHL in four selected mouse stains is correlated with the loss of ribbon synapses, being most severe for the strains C57BL/6NTac and C57BL/6J, less so for C57BL/6NTac -Repaired and lowest for C3H/HeJ.

Exocytosis in mouse vestibular Type II hair cells shows a high-order Ca dependence that is independent of synaptotagmin-4.

Mature hair cells transduce information over a wide range of stimulus intensities and frequencies for prolonged periods of time. The efficiency of such a demanding task is reflected in the characteristics of exocytosis at their specialized presynaptic ribbons. Ribbons are electron-dense structures able to tether a large number of releasable vesicles allowing them to maintain high rates of vesicle release.