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*  Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells | COMD News
Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials were intrinsically generated by immature IHCs of altricial rodents and that apical IHCs showed bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter acetylcholine fine-tunes the IHC's resting membrane potential (Vm), and as such is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the Vm of apical and basal IHCs by triggering small-conductance Ca2+-activated K+ (SK2) channels. We propose that the ...
  https://callierlibrary.wordpress.com/2011/05/26/position-dependent-patterning-of-spontaneous-action-potentials-in-immature-cochlear-inner-hair-cells/
*  Electrical Properties and Functional Expression of Ionic Channels in Cochlear Inner Hair Cells of Mice Lacking the α10...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
  http://pubmedcentralcanada.ca/pmcc/articles/PMC2674205/
*  Exocytotic machineries of vestibular type I and cochlear ribbon synapses display similar intrinsic otoferlin-dependent Ca2+...
Link to Pubmed [PMID] - 25122888. J. Neurosci. 2014 Aug;34(33):10853-69. The hair cell ribbon synapses of the mammalian auditory and vestibular systems differ greatly in their anatomical organization and firing properties. Notably, vestibular Type I hair cells (VHC-I) are surrounded by a single calyx-type afferent terminal that receives input from several ribbons, whereas cochlear inner hair cells (IHCs) are contacted by several individual afferent boutons, each facing a single ribbon. The specificity of the presynaptic molecular mechanisms regulating transmitter release at these different sensory ribbon synapses is not well understood. Here, we found that exocytosis during voltage activation of Ca(2+) channels displayed higher Ca(2+) sensitivity, 10 mV more negative half-maximum activation, and a smaller dynamic range in VHC-I than in IHCs. VHC-I had a ...
  https://research.pasteur.fr/en/publication/exocytotic-machineries-of-vestibular-type-i-and-cochlear-ribbon-synapses-display-similar-intrinsic-otoferlin-dependent-ca2-sensitivity-but-a-different-coupling-to-ca2-channels/
*  The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation...
The hair cells of the inner ear seem to be specified properly as they express many of the typical hair cell markers such as myosin VI/VIIa, Math1 and Brn3c. Thus, Gfi1 is not required for the specification of hair cells as they are formed in both the vestibule and the cochlea. However, the loss of Gfi1 seems to affect the vestibular and cochlear hair cells differently. In the vestibule, the hair cells are morphologically abnormal at the earliest stages of hair cell differentiation and at all subsequent stages. In addition, hair cells are not specifically localized to a lumenal monolayer, and are more variable in size and shape. This disorganization of hair ...
  http://dev.biologists.org/content/130/1/221
*  An Earful of AChR α9 | Science Signaling
Even before hearing becomes active, there is a transient cholinergic innervation in the developing mammalian inner ear. The physiological significance of these synapses has never been demonstrated. Glowatzki and Fuchs show that the novel neuronal nicotinic acetylcholine receptor α9 is functionally present in neonatal cochlear inner hair cells and behaves like a true acetylcholine receptor. Its stimulation results in the activation of a fast, calcium-dependent potassium channel. Acetylcholine thus inhibits afferent activity and acts to impose rhythmicity onto the immature auditory pathway.. Glowatzki, E., and Fuchs, P.A. (2000) Cholinergic synaptic inhibition of inner hair cells in the neonatal mammalian cochlea. Science 288: 2366-2368. [Abstract] [Full Text]. ...
  http://stke.sciencemag.org/content/2000/39/tw11
*  Ribbon synapse - Wikipedia
The ribbon synapse is a type of neuronal synapse characterized by the presence of an electron-dense structure, the synaptic ribbon, that holds vesicles close to the active zone. It is characterized by a tight vesicle-calcium channel coupling that promotes rapid neurotransmitter release and sustained signal transmission. Ribbon synapses undergo a cycle of exocytosis and endocytosis in response to graded changes of membrane potential. It has been proposed that most ribbon synapses undergo a special type of exocytosis based on coordinated multivesicular release. This interpretation has recently been questioned at the inner hair cell ribbon synapse, where it has been instead proposed that exocytosis is described by uniquantal (i.e., univesicular) release shaped by a flickering vesicle fusion pore. These unique features specialize the ribbon synapse to enable extremely fast, precise and sustained neurotransmission, which is critical for the perception of complex senses such as ...
  https://en.wikipedia.org/wiki/Ribbon_synapse
*  Inner ear hair cells, SEM - Stock Image F004/3259 - Science Photo Library
Inner ear hair cells. Coloured scanning electron micrograph (SEM) of sensory hair cells in the cochlea of the inner ear. The crescent-shaped arrangements of hairs across top are the stereocilia. Each crescent lies atop a single cell. Magnification: x1000 when printed at 10 centimetres wide. - Stock Image F004/3259
  http://www.sciencephoto.com/media/437272/view
*  A synaptic F-actin network controls otoferlin-dependent exocytosis in auditory inner hair cells • Research - Institut Pasteur
Link to Pubmed [PMID] - 26568308. Elife 2015;4. We show that a cage-shaped F-actin network is essential for maintaining a tight spatial organization of Cav1.3 Ca(2+) channels at the synaptic ribbons of auditory inner hair cells. This F-actin network is also found to provide mechanosensitivity to the Cav1.3 channels when varying intracellular hydrostatic pressure. Furthermore, this F-actin mesh network attached to the synaptic ribbons directly influences the efficiency of otoferlin-dependent exocytosis and its sensitivity to intracellular hydrostatic pressure, independently of its action on the Cav1.3 channels. We propose a new mechanistic model for vesicle exocytosis in auditory hair cells where the rate of vesicle recruitment to the ribbons is directly controlled by a synaptic F-actin network and changes in intracellular hydrostatic pressure.. ...
  https://research.pasteur.fr/en/publication/a-synaptic-f-actin-network-controls-otoferlin-dependent-exocytosis-in-auditory-inner-hair-cells/
*  Click to print
About 95 percent of sound input to the brain comes from the ear's inner hair cells.. "These inner hair cells are like spark plugs in an 8-cylinder engine," says Salvi. "A car won't run well if you remove half of those spark plugs, but people can still present with normal hearing thresholds if they've lost half or even three-quarters of their inner hair cells.". Ear damage reduces the signal that goes the brain. That results in trouble hearing, but that's not what's happening here, because the brain "has a central gain control, like a radio, the listener can turn up the volume control to better hear a distant station." Salvi says.. Sound is converted to neural activity by the inner hair cells in the auditory part of the ear, called the cochlea.. Sound-evoked neural activity then travels from ...
  http://speciality.medicaldialogues.in/hearing-tests-miss-common-form-of-hearing-loss-study-shows/
*  Hille Lecture on inner ear hair cell research | UW News
Corey's research focuses on understanding the cellular and molecular basis of hearing. A specialized cell of the inner ear, called a hair cell, converts the mechanical stimulus of a sound wave into an electrical stimulus that is sent to the brain. These hair cells have a bundle of hair-like protrusions emanating from the top surface of the cell. These hairs are connected by fine filaments that are stretched every time the hair bundle is deflected by a sound vibration. The filaments are, in turn, connected directly to proteins called ion channels that respond to the stretch by producing an electrical current across the membrane ...
  http://www.washington.edu/news/2003/04/03/hille-lecture-on-inner-ear-hair-cell-research/
*  A Biophysical Model of Cochlear Processing: Intensity Dependence of Pure Tone Responses.
A mathematical model of cochlear processing is developed to account for the nonlinear dependence of frequency selectivity on intensity in inner hair cell and auditory nerve fiber responses. The model describes the transformation from acoustic stimulus to intracellular hair cell potentials in the cochlea. It incorporates a linear formulation of basilar membrane mechanics and subtectorial fluid-cilia displacement coupling, and simplified description of the inner hair cell nonlinear transduction process. The analysis at this stage is restricted to low-frequency single tones. The computed responses to single tone inputs exhibit the experimentally observed nonlinear effects of increasing intensity such as the increase in the bandwidth of frequency selectivity and the downward shift of the best frequency. In the model, the first effect is primarily due to the saturating effect of the ...
  https://drum.lib.umd.edu/handle/1903/4459
*  NIOSHTIC-2 Publications Search - 00186996 - The consistent occurrence of a striated organelle (Friedmann body) in the inner...
The consistent occurrence of the striated bodies in the inner hair cells of normal chinchillas was reported. Both cochleas from ten normal chinchillas 1 to 7 years of age were examined. In all cases for the over 70 inner hair cells sectioned, when serial sections were examined, striated bodies were found to be located in every inner hair cell. Striated bodies were not observed in the outer hair ce
  https://www.cdc.gov/niosh/nioshtic-2/00186996.html
*  15th International Mouse Genome Conference (2001)
Institutions: MRC Mammalian Genetics Unit and Mouse Genome Centre, MRC Institute of Hearing Research Genetic deafness is highly prevalent in the human population, affecting 1 in 2000 births. Many of these show primary abnormalities of the sensory epithelia of the inner ear, as do several mouse mutants. In the whirler (wi) mutant the stereocilia of the inner hair cells of the cochlear duct are considerably shorter than wild-type while outer hair cell stereocilia take on a more rounded U shape compared to the normal V or W shape. Cloning of the defective gene underlying wi will provide insight into the molecular processes involved in normal development of stereocilia as well as providing valuable insights into the causes of neuroepithelial deafness. The wi non-recombinant region is contained within a minimal tiling path consisting of 2 BACs and a PAC. One of the BACs has been used in transgenic rescue ...
  http://www.imgs.org/Archive/abstracts/2001abstracts/mburu.shtml
*  Inner Ear Hair Cell Regeneration - Maybe We Can Know More | Tinnitus Talk Support Forum
Dear members of Tinnitus Talk, As we are all hoping that a cure for (subjective) tinnitus will come in the near future, I created this thread to try...
  https://www.tinnitustalk.com/threads/inner-ear-hair-cell-regeneration-%E2%80%94-maybe-we-can-know-more.3131/
*  Hair cell synaptic dysfunction, auditory fatigue and thermal sensitivity in otoferlin Ile515Thr mutants | The EMBO Journal
The multi‐C2 domain protein otoferlin is required for hearing and mutated in human deafness. Some OTOF mutations cause a mild elevation of auditory thresholds but strong impairment of speech perception. At elevated body temperature, hearing is lost. Mice homozygous for one of these mutations, OtofI515T/I515T, exhibit a moderate hearing impairment involving enhanced adaptation to continuous or repetitive sound stimulation. In OtofI515T/I515T inner hair cells (IHCs), otoferlin levels are diminished by 65%, and synaptic vesicles are enlarged. Exocytosis during prolonged stimulation is strongly reduced. This indicates that otoferlin is critical for the reformation of properly sized and fusion‐competent synaptic vesicles. Moreover, we found sustained exocytosis and sound encoding to scale with the amount of otoferlin at the plasma membrane. We identified a 20 amino acid motif including an RXR motif, presumably present in human but not in mouse ...
  http://d2ni3bh4dzb2ig.cloudfront.net/content/35/23/2519
*  Espn - Espin - Rattus norvegicus (Rat) - Espn gene & protein
Multifunctional actin-bundling protein. Plays a major role in regulating the organization, dimension, dynamics and signaling capacities of the actin filament-rich microvilli in the mechanosensory and chemosensory cells (PubMed:9763424). Required for the assembly and stabilization of the stereociliary parallel actin bundles. Plays a crucial role in the formation and maintenance of inner ear hair cell stereocilia. Involved in the elongation of actin in stereocilia. In extrastriolar hair cells, required for targeting MYO3B to stereocilia tips, and for regulation of stereocilia diameter and staircase formation (By similarity).
  http://www.uniprot.org/uniprot/Q63618
*  Dabdoub, Alain | Laboratory Medicine and Pathobiology --- University of Toronto
Hearing loss is the fastest growing and one of the most prevalent chronic conditions today affecting 600 million people worldwide. Furthermore, hearing impairment is one of the most common birth defects in humans and numerous forms are due to defects in the developmental pathways responsible for formation of the cochlea - the hearing organ. In addition to its basic biological function, the complex development of the cochlea enables us to study organogenesis, pluripotency, plasticity, cell fate specification, differentiation and pattern formation - processes that are essential aspects of development for all biological systems.. Many cases of acquired hearing impairment are attributed to damage or loss of inner ear hair cells - cells that are responsible for detecting sound in our environment, and inner ear neurons - cells that are responsible for transmitting sound information from the hair ...
  http://lmp.utoronto.ca/research/faculty-research-database/dabdoub-alain
*  calcium - Dwight Bergles Laboratory
Spontaneous electrical activity is a common feature of sensory systems during early development. This sensory-independent neuronal activity has been implicated in promoting their survival and maturation, as well as growth and refinement of their projections to yield circuits that can rapidly extract information about the external world. Periodic bursts of action potentials occur in auditory neurons of mammals before hearing onset. This activity is induced by inner hair cells (IHCs) within the developing cochlea, which establish functional connections with spiral ganglion neurons (SGNs) several weeks before they are capable of detecting external sounds. During this pre-hearing period, IHCs fire periodic bursts of Ca(2+) action potentials that excite SGNs, triggering brief but intense periods of activity that pass through auditory centers of the brain. Although spontaneous activity requires input from IHCs, there is ongoing ...
  http://bergleslab.com/index.php/tag/calcium/
*  Original Research - Page 2 - Dwight Bergles Laboratory
Spontaneous electrical activity is a common feature of sensory systems during early development. This sensory-independent neuronal activity has been implicated in promoting their survival and maturation, as well as growth and refinement of their projections to yield circuits that can rapidly extract information about the external world. Periodic bursts of action potentials occur in auditory neurons of mammals before hearing onset. This activity is induced by inner hair cells (IHCs) within the developing cochlea, which establish functional connections with spiral ganglion neurons (SGNs) several weeks before they are capable of detecting external sounds. During this pre-hearing period, IHCs fire periodic bursts of Ca(2+) action potentials that excite SGNs, triggering brief but intense periods of activity that pass through auditory centers of the brain. Although spontaneous activity requires input from IHCs, there is ongoing ...
  http://bergleslab.com/index.php/category/publications/original-research/page/2/
*  Publications - Page 2 - Dwight Bergles Laboratory
Spontaneous electrical activity is a common feature of sensory systems during early development. This sensory-independent neuronal activity has been implicated in promoting their survival and maturation, as well as growth and refinement of their projections to yield circuits that can rapidly extract information about the external world. Periodic bursts of action potentials occur in auditory neurons of mammals before hearing onset. This activity is induced by inner hair cells (IHCs) within the developing cochlea, which establish functional connections with spiral ganglion neurons (SGNs) several weeks before they are capable of detecting external sounds. During this pre-hearing period, IHCs fire periodic bursts of Ca(2+) action potentials that excite SGNs, triggering brief but intense periods of activity that pass through auditory centers of the brain. Although spontaneous activity requires input from IHCs, there is ongoing ...
  http://bergleslab.com/index.php/category/publications/page/2/
*  Vestibular Regeneration - Experimental Models and Clinical Implications.
Therapies aimed at the protection and/or regeneration of inner ear hair cells are of great interest given the significant monetary and quality of life impact of balance disorders. Different viral vectors have been shown to transfect various cell type
  http://www.biomedsearch.com/nih/Vestibular-Regeneration-Experimental-Models-Clinical/22303988.html
*  New Insights into the Development of Ciliopathies - Healthcanal.com : Healthcanal.com
To date, it is still not clear how proteins regulate planar cell polarity (PCP) or the positioning of the basal body (BB) and cilia. Scientists of Helmholtz Zentrum München have now taken an important step in elucidating this mechanism. Moritz Gegg and Professor Dr. Heiko Lickert of the Institute of Diabetes and Regeneration Research (IDR) have published their new findings in the journal "eLIFE".. "Epithelial cell layers line all of the inner and outer body and organ surfaces in the human body, for example in the lung, intestine, pancreas and in the inner ear," said Moritz Gegg. Cilia - small, hair-like, microtubule-based structures - project from BBs and are precisely positioned on many of these epithelial cells. "Only through this exact positioning can cilia movements be coordinated so precisely that for example mucus can be transported from the lung or sound can be perceived from sensory inner ear hair ...
  https://www.healthcanal.com/medical-breakthroughs/56749-new-insights-into-the-development-of-ciliopathies.html
*  October 2016 - Page 2 - How NF-B is activated: the role of the IB kinase (IKK) complex
History In the cochlea patterning of the organ of Corti is tightly regulated to produce a single row of sound detecting inner hair cells and three rows of outer hair cells which amplify and refine the signal. While their signaling pathways and mechanisms remain to be fully elucidated all four R-Spondins have been shown to function as positive regulators of canonical Wnt signaling and Rspo3 has been shown to function in Wnt planar cell polarity (PCP) signaling (Kazanskaya et al. 2004 Nam et al. 2006 Binnerts et al. 2007 Chassot et al. 2008 Kim et al. 2008 Lu et al. 2008 Carmon et al. 2011 de Lau et al. 2011 Glinka et al. 2011 Ohkawara et al. 2011 It is likely that R-Spondins prolong a cell's ability to respond to Wnt signaling by regulating Wnt receptor turnover at the membrane (Binnerts et al. 2007 Carmon et al. 2011 de Lau et al. 2011 Glinka et al. 2011 Ohkawara et al. 2011 ...
  http://cancercurehere.com/?m=201610&paged=2
*  Topics on Deaf Japan: November 2011
The researchers suggest that the device could be described as the "technological regeneration of [inner ear] hair cells," but caution that the device's electrical output must be increased to stimulate auditory primary neurons in the ear like current implants. Together, the results suggest that one day deaf patients may be able to use small prosthetics that mimic natural cochlear function, without the need for a battery. The results were published in PNAS ...
  https://deafjapan.blogspot.jp/2011/11/
*  Plus it
Real-time qPCR analysis of all α2δ subunit isoforms indicated that neonatal IHCs express mainly α2δ2, whereas mature IHCs exclusively express α2δ2 mRNA. The low expression of α2δ3 mRNA detected in IHCs before hearing onset is in accordance with a small reduction of the Ba2+ current density in immature IHCs of α2δ3−/− mice (Pirone et al., 2014). α2δ2 mRNA was clearly present in both immature and mature IHCs and OHCs. Its low level at P20-P25 can be explained by the downregulation of Cav1.3 currents during development to only one-third of the level present at P6 in IHCs (Beutner and Moser, 2001; Johnson et al., 2005) and similarly also in OHCs (Knirsch et al., 2007). The fact that α2δ1, α2δ3, and α2δ4 mRNA were not detected indicates that α2δ2 is the dominant α2δ isoform that forms Ca2+ channels with Cav1.3 and Cavβ2 in mature IHCs. Interestingly, this L-type channel complex (CaV1.3/β2/α2δ2) is distinct from the P/Q-type channel complex in cerebellar Purkinje cells, ...
  http://www.jneurosci.org/content/36/43/11024