A5068080149- Hearing, Cochlea, Tinnitus, Genetics
- Hearing Loss and Rehabilitation
- Ion Channels and Receptors
- Vestibular and auditory disorders
- Biochemical Analysis and Sensing Techniques
- Acoustic Wave Phenomena Research
- Connexins and lens biology
- Ion channel regulation and function
- Neuroscience of respiration and sleep
- Cancer-related molecular mechanisms research
- Neuroscience and Neuropharmacology Research
- Congenital heart defects research
- Marine animal studies overview
- Erythrocyte Function and Pathophysiology
- Photoreceptor and optogenetics research
- Animal Vocal Communication and Behavior
- RNA regulation and disease
- Neural dynamics and brain function
- Ear Surgery and Otitis Media
- Escherichia coli research studies
- MicroRNA in disease regulation
- RNA and protein synthesis mechanisms
- Yersinia bacterium, plague, ectoparasites research
- Neuropeptides and Animal Physiology
- Congenital limb and hand anomalies
University of Sheffield
2016-2025
Neuroscience Institute
2025
University of Oxford
2015
University of Sussex
2001-2009
Outer hair cells (OHCs) provide amplification in the mammalian cochlea using somatic force generation underpinned by voltage-dependent conformational changes of motor protein prestin. However, prestin must be gated membrane potential on a cycle-by-cycle basis and periodic component receptor may greatly attenuated low-pass filtering due to OHC time constant (τ(m)), questioning functional relevance this mechanism. Here, we measured τ(m) from OHCs with range characteristic frequencies (CF)...
Myosin-VIIA (MYO7A) is an unconventional myosin responsible for syndromic (Usher 1B) or nonsyndromic forms of deafness in humans when mutated. In the cochlea, MYO7A expressed hair cells, where it believed to act as motor protein tensioning mechanoelectrical transducer (MET) channels, thus setting their resting open probability ( P o ). However, direct evidence this unique role mature cells lacking. Here, we show that has a distinct being crucial structural integrity bundles. Postnatal...
Graphical Abstract figure legend HCN channels play an evolutionarily conserved pacemaker role in renal pelvic smooth muscle (RPSM) of lower and higher order mammals. The function hyperpolarization-activated cation (HCN) pacemakers remains controversial. Renal trigger contractions that expel waste from the kidney, have been localized to these tissues. To date, however, mechanisms underlying RPSM activity remain elusive. was investigated both (top left) (bottom mammalian models, which exhibit...
Developmental changes in electrophysiological membrane properties of mouse cochlear inner hair cells (IHCs) were studied from just after terminal differentiation up to functional maturity. As early as embryonic day 14.5 (E14.5) newly differentiated IHCs express a very small outward K+ current that is largely insensitive 4-aminopyridine (4-AP). One later the inward rectifier, IK1, first observed. These immature initially exhibit only slow graded voltage responses under clamp. From E17.5...
Developmental changes in the coupling between Ca2+ entry and exocytosis were studied mouse inner hair cells (IHCs) which, together with afferent endings, form primary synapse of mammalian auditory system. currents (ICa) membrane capacitance (DeltaCm) recorded using whole-cell voltage clamp from maintained at body temperature, physiological (1.3 mM) extracellular Ca2+. The magnitudes both ICa DeltaCm increased maturation embryonic stages until postnatal day 6 (P6). Subsequently, gradually...
Significance In the inner ear, sensory receptor cells (hair cells) signal reception of sound. They do so by converting mechanical input, due to sound waves moving hair bundles on these cells, into electrical current through ion channels situated at tips bundles. To keep receptors operating their maximum sensitivity, declines rapidly, a process known as adaptation. nonmammalian vertebrates, Ca 2+ ions entering mechanosensitive drive adaptation, but it has been questioned whether this...
Hair cells of the mammalian cochlea are specialized for dynamic coding sound stimuli. The transduction waves into electrical signals depends upon mechanosensitive hair bundles that project from cell's apical surface. Each stereocilium within a bundle is composed uniformly polarized and tightly packed actin filaments. Several stereociliary proteins have been shown to be associated with development function known cause deafness in mice humans when mutated. growth stereociliar core dynamically...
The neural crest (NC) is a multipotent embryonic cell population that generates distinct types in an axial position-dependent manner. production of NC cells from human pluripotent stem (hPSCs) valuable approach to study biology. However, the origin trunk remains undefined and current vitro differentiation strategies induce only modest yield cells. Here we show hPSC-derived progenitors, posteriorly-located drivers axis elongation, give rise their derivatives. Moreover, define molecular...
Before the onset of hearing at postnatal day 12, mouse inner hair cells (IHCs) produce spontaneous and evoked action potentials. These spikes are likely to induce neurotransmitter release onto auditory nerve fibres. Since immature IHCs express both alpha1D (Cav1.3) Ca2+ Na+ currents that activate near resting potential, we examined whether these two conductances involved in shaping Both had extremely rapid activation kinetics, followed by fast complete voltage-dependent inactivation for...
From just after birth, mouse inner hair cells (IHCs) expressed a Ca(2+)-activated K(+) current that was reduced by intracellular BAPTA at concentrations >or= 1 mM. The block of this nifedipine suggests the direct involvement Ca(v)1.3 Ca(2+) channels in its activation. On basis high sensitivity to apamin (K(D) 360 pM) it identified as small-conductance (SK), probably SK2. A similar also found outer (OHCs) from beginning second postnatal week. In both cell types appearance SK coincided with...
The mammalian cochlea is specialized to recognize and process complex auditory signals with remarkable acuity temporal precision over a wide frequency range. quality of the information relayed afferent fibers mainly depends on transfer characteristics inner hair cell (IHC) ribbon synapses. To investigate biophysical properties synaptic machinery, we measured changes in membrane capacitance (Δ C m ) low-frequency (apical region, ∼300 Hz) high-frequency (basal, ∼30 kHz) gerbil IHCs maintained...
The deafness (dn) and Beethoven (Bth) mutant mice are models for profound congenital (DFNB7/B11) progressive hearing loss (DFNA36), respectively, caused by recessive dominant mutations of transmembrane cochlear-expressed gene 1 (TMC1), which encodes a protein unknown function. In the mouse cochlea Tmc1 is expressed in both outer (OHCs) inner (IHCs) hair cells from early stages development. Immature seem normal appearance biophysical properties. From around P8 OHCs P12 IHCs, mutants fail to...
Mammalian cochlear inner hair cells (IHCs) are specialized to process developmental signals during immature stages and sound stimuli in adult animals. These conveyed onto auditory afferent nerve fibres. Neurotransmitter release at IHC ribbon synapses is controlled by L-type Ca(V)1.3 Ca(2+) channels, the biophysics of which still unknown native mammalian cells. We have investigated localization elementary properties channels mouse IHCs under near-physiological recording conditions. cell...
The ribbon synapses of auditory inner hair cells (IHCs) undergo morphological and electrophysiological transitions during cochlear development. Here we report that myosin VI (Myo6), an actin-based motor protein involved in genetic forms deafness, is necessary for some these changes to occur. By using post-embedding immunogold electron microscopy, showed Myo6 present at the IHC synaptic active zone. In Snell's waltzer mutant mice, which lack Myo6, ionic currents synapse maturation proceeded...
MicroRNAs (miRNAs) are small noncoding RNAs able to regulate a broad range of protein-coding genes involved in many biological processes. miR-96 is sensory organ-specific miRNA expressed the mammalian cochlea during development. Mutations cause nonsyndromic progressive hearing loss humans and mice. The mouse mutant diminuendo has single base change seed region Mir96 gene leading widespread changes expression genes. We have used this explore role maturation auditory organ. found that...
Mechanotransduction in the mammalian auditory system depends on mechanosensitive channels hair bundles that project from apical surface of sensory cells. Individual stereocilia within each bundle contain a core tightly packed actin filaments, whose length is dynamically regulated during development and adult. We show actin-binding protein epidermal growth factor receptor pathway substrate 8 (Eps8)L2, member Eps8-like family, newly identified localized at tips both cochlear vestibular It has...
The development of neural circuits relies on spontaneous electrical activity that occurs during immature stages development. In the developing mammalian auditory system, calcium action potentials are generated by inner hair cells (IHCs), which form primary sensory synapse. It remains unknown whether this is required for functional maturation system. We found sensory-independent controls synaptic in IHCs. used a mouse model potassium channel SK2 normally overexpressed, but can be modulated...
The transduction of sound into electrical signals depends on mechanically sensitive ion channels in the stereociliary bundle. molecular composition this mechanoelectrical transducer (MET) channel is not yet known. Transmembrane channel-like protein isoforms 1 (TMC1) and 2 (TMC2) have been proposed to form part MET channel, although their exact roles are still unclear. Using Beethoven ( Tmc1 Bth/Bth ) mice, which an M412K point mutation TMC1 that adds a positive charge, we found Ca 2+...
Mutations in the genes encoding for gap junction proteins connexin 26 (Cx26) and 30 (Cx30) have been linked to syndromic nonsyndromic hearing loss mice humans. The release of ATP from hemichannels cochlear nonsensory cells has proposed be main trigger action potential activity immature sensory inner hair (IHCs), which is crucial refinement developing auditory circuitry. Using knock-out mice, we show that IHCs fire spontaneous potentials even absence ATP-dependent intercellular Ca 2+...
Article25 February 2019Open Access Transparent process Coordinated calcium signalling in cochlear sensory and non-sensory cells refines afferent innervation of outer hair Federico Ceriani orcid.org/0000-0002-5366-341X Department Biomedical Science, University Sheffield, UK Search for more papers by this author Aenea Hendry Jing-Yi Jeng Stuart L Johnson Friederike Stephani Center Integrative Physiology Molecular Medicine (CIPMM), Saarland University, Homburg, Germany Jennifer Olt Matthew C...
In the adult auditory organ, mechanoelectrical transducer (MET) channels are essential for transducing acoustic stimuli into electrical signals. absence of incoming sound, a fraction MET on top sensory hair cells open, resulting in sustained depolarizing current. By genetically manipulating vivo expression molecular components apparatus, we show that during pre-hearing stages current is establishing electrophysiological properties mature inner (IHCs). If abolished IHCs, they revert showing...