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Synaptic ribbon

Richard A Altschuler, Noel Wys, Diane Prieskorn, Cathy Martin, Susan DeRemer, Sanford Bledsoe, Josef M Miller
Noise overstimulation can induce loss of synaptic ribbons associated with loss of Inner Hair Cell - Auditory Nerve synaptic connections. This study examined if systemic administration of Piribedil, a dopamine agonist that reduces the sound evoked auditory nerve compound action potential and/or Memantine, an NMDA receptor open channel blocker, would reduce noise-induced loss of Inner Hair Cell ribbons. Rats received systemic Memantine and/or Piribedil for 3 days before and 3 days after a 3 hour 4 kHz octave band noise at 117 dB (SPL)...
September 30, 2016: Scientific Reports
Tobias Moser, Christian Vogl
The inner ear uses specialized synapses to indefatigably transmit sound information from hair cells to spiral ganglion neurons at high rates with submillisecond precision. The emerging view is that hair cell synapses achieve their demanding function by employing an unconventional presynaptic molecular composition. Hair cell active zones hold the synaptic ribbon, an electron-dense projection made primarily of RIBEYE, which tethers a halo of synaptic vesicles and is thought to enable a large readily releasable pool of vesicles and to contribute to its rapid replenishment...
2016: F1000Research
Lara Li Hesse, Warren Bakay, Hui-Ching Ong, Lucy Anderson, Jonathan Ashmore, David McAlpine, Jennifer Linden, Roland Schaette
The occurrence of tinnitus can be linked to hearing loss in the majority of cases, but there is nevertheless a large degree of unexplained heterogeneity in the relation between hearing loss and tinnitus. Part of the problem might be that hearing loss is usually quantified in terms of increased hearing thresholds, which only provides limited information about the underlying cochlear damage. Moreover, noise exposure that does not cause hearing threshold loss can still lead to "hidden hearing loss" (HHL), i.e...
2016: Frontiers in Neurology
Yvonne Ou, Rebecca E Jo, Erik M Ullian, Rachel O L Wong, Luca Della Santina
UNLABELLED: Key issues concerning ganglion cell type-specific loss and synaptic changes in animal models of experimental glaucoma remain highly debated. Importantly, changes in the structure and function of various RGC types that occur early, within 14 d after acute, transient intraocular pressure elevation, have not been previously assessed. Using biolistic transfection of individual RGCs and multielectrode array recordings to measure light responses in mice, we examined the effects of laser-induced ocular hypertension on the structure and function of a subset of RGCs...
August 31, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jason Seth Rothman, Laszlo Kocsis, Etienne Herzog, Zoltan Nusser, Robin Angus Silver
Encoding continuous sensory variables requires sustained synaptic signalling. At several sensory synapses, rapid vesicle supply is achieved via highly mobile vesicles and specialized ribbon structures, but how this is achieved at central synapses without ribbons is unclear. Here we examine vesicle mobility at excitatory cerebellar mossy fibre synapses which sustain transmission over a broad frequency bandwidth. Fluorescent recovery after photobleaching in slices from VGLUT1(Venus) knock-in mice reveal 75% of VGLUT1-containing vesicles have a high mobility, comparable to that at ribbon synapses...
2016: ELife
Pezhman Salehi, Anthony Myint, Young J Kim, Marshall X Ge, Joel Lavinsky, Maria K Ho, Amanda L Crow, Charlene Cruz, Maya Monges-Hernadez, Juemei Wang, Jaana Hartiala, Li I Zhang, Hooman Allayee, Aldons J Lusis, Takahiro Ohyama, Rick A Friedman
This study aimed to investigate the genetic causes of vestibular dysfunction. We used vestibular sensory-evoked potentials (VsEPs) to characterize the vestibular function of 35 inbred mouse strains selected from the Hybrid Mouse Diversity Panel and demonstrated strain-dependent phenotypic variation in vestibular function. Using these phenotypic data, we performed the first genome-wide association study controlling for population structure that has revealed two highly suggestive loci, one of which lies within a haplotype block containing five genes (Stard6, 4930503L19Rik, Poli, Mbd2, Dcc) on Chr...
October 2016: Journal of the Association for Research in Otolaryngology: JARO
Katsuki Niwa, Kunio Mizutari, Toshiyasu Matsui, Takaomi Kurioka, Takeshi Matsunobu, Satoko Kawauchi, Yasushi Satoh, Shunichi Sato, Akihiro Shiotani, Yasushi Kobayashi
The ear is the organ that is most sensitive to blast overpressure, and ear damage is most frequently seen after blast exposure. Blast overpressure to the ear results in sensorineural hearing loss, which is untreatable and is often associated with a decline in the quality of life. In this study, we used a rat model to demonstrate the pathophysiological and structural changes in the inner ear that replicate pure sensorineural hearing loss associated with blast injury using laser-induced shock wave (LISW) without any conductive hearing loss...
2016: Scientific Reports
Min Young Lee, Takaomi Kurioka, Megan M Nelson, Diane M Prieskorn, Donald L Swiderski, Yohei Takada, Lisa A Beyer, Yehoash Raphael
Synaptopathy in the cochlea occurs when the connection between inner hair cells and the auditory nerve is disrupted, leading to impaired hearing and nerve degeneration. Experiments using transgenic mice have shown that overexpression of NT3 by supporting cells repairs synaptopathy caused by overstimulation. To accomplish such therapy in the clinical setting, it would be necessary to activate the neurotrophin receptor on auditory neurons by other means. Here we test the outcome of NT3 overexpression using viral-mediated gene transfer into the perilymph versus the endolymph of the normal guinea pig cochlea...
2016: Molecular Therapy. Methods & Clinical Development
Christian Vogl, Iliana Panou, Gulnara Yamanbaeva, Carolin Wichmann, Sara J Mangosing, Fabio Vilardi, Artur A Indzhykulian, Tina Pangršič, Rosamaria Santarelli, Montserrat Rodriguez-Ballesteros, Thomas Weber, Sangyong Jung, Elena Cardenas, Xudong Wu, Sonja M Wojcik, Kelvin Y Kwan, Ignacio Del Castillo, Blanche Schwappach, Nicola Strenzke, David P Corey, Shuh-Yow Lin, Tobias Moser
The transmembrane recognition complex (TRC40) pathway mediates the insertion of tail-anchored (TA) proteins into membranes. Here, we demonstrate that otoferlin, a TA protein essential for hair cell exocytosis, is inserted into the endoplasmic reticulum (ER) via the TRC40 pathway. We mutated the TRC40 receptor tryptophan-rich basic protein (Wrb) in hair cells of zebrafish and mice and studied the impact of defective TA protein insertion. Wrb disruption reduced otoferlin levels in hair cells and impaired hearing, which could be restored in zebrafish by transgenic Wrb rescue and otoferlin overexpression...
July 25, 2016: EMBO Journal
Luca Della Santina, Sidney P Kuo, Takeshi Yoshimatsu, Haruhisa Okawa, Sachihiro C Suzuki, Mrinalini Hoon, Kotaro Tsuboyama, Fred Rieke, Rachel O L Wong
Excitatory and inhibitory neurons in the CNS are distinguished by several features, including morphology, transmitter content, and synapse architecture [1]. Such distinctions are exemplified in the vertebrate retina. Retinal bipolar cells are polarized glutamatergic neurons receiving direct photoreceptor input, whereas amacrine cells are usually monopolar inhibitory interneurons with synapses almost exclusively in the inner retina [2]. Bipolar but not amacrine cell synapses have presynaptic ribbon-like structures at their transmitter release sites...
August 8, 2016: Current Biology: CB
Kayla Hill, Hu Yuan, Xianren Wang, Su-Hua Sha
UNLABELLED: Noise-induced hearing loss (NIHL) is a major unresolved public health problem. Here, we investigate pathomechanisms of sensory hair cell death and suggest a novel target for protective intervention. Cellular survival depends upon maintenance of energy homeostasis, largely by AMP-activated protein kinase (AMPK). In response to a noise exposure in CBA/J mice, the levels of phosphorylated AMPKα increased in hair cells in a noise intensity-dependent manner. Inhibition of AMPK via siRNA or the pharmacological inhibitor compound C attenuated noise-induced loss of outer hair cells (OHCs) and synaptic ribbons, and preserved auditory function...
July 13, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Gema Esquiva, Aaron Avivi, Jens Hannibal
The blind mole rat, Spalax ehrenbergi, can, despite severely degenerated eyes covered by fur, entrain to the daily light/dark cycle and adapt to seasonal changes due to an intact circadian timing system. The present study demonstrates that the Spalax retina contains a photoreceptor layer, an outer nuclear layer (ONL), an outer plexiform layer (OPL), an inner nuclear layer (INL), an inner plexiform layer (IPL), and a ganglion cell layer (GCL). By immunohistochemistry, the number of melanopsin (mRGCs) and non-melanopsin bearing retinal ganglion cells was analyzed in detail...
2016: Frontiers in Neuroanatomy
Norbert Babai, Anna Sendelbeck, Hanna Regus-Leidig, Michaela Fuchs, Jasmin Mertins, Kerstin Reim, Nils Brose, Andreas Feigenspan, Johann Helmut Brandstätter
UNLABELLED: Complexins (Cplxs) are SNARE complex regulators controlling the speed and Ca(2+) sensitivity of SNARE-mediated synaptic vesicle fusion. We have shown previously that photoreceptor ribbon synapses in mouse retina are equipped with Cplx3 and Cplx4 and that lack of both Cplxs perturbs photoreceptor ribbon synaptic function; however, Cplx3/4 function in photoreceptor synaptic transmission remained elusive. To investigate Cplx3/4 function in photoreceptor ribbon synapses, voltage-clamp recordings from postsynaptic horizontal cells were performed in horizontal slice preparations of Cplx3/4 wild-type (WT) and Cplx3/4 double knock-out (DKO) mice...
June 22, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Hiroshi Nishimune, Yomna Badawi, Shuuichi Mori, Kazuhiro Shigemoto
Presynaptic active zones play a pivotal role as synaptic vesicle release sites for synaptic transmission, but the molecular architecture of active zones in mammalian neuromuscular junctions (NMJs) at sub-diffraction limited resolution remains unknown. Bassoon and Piccolo are active zone specific cytosolic proteins essential for active zone assembly in NMJs, ribbon synapses, and brain synapses. These proteins are thought to colocalize and share some functions at active zones. Here, we report an unexpected finding of non-overlapping localization of these two proteins in mouse NMJs revealed using dual-color stimulated emission depletion (STED) super resolution microscopy...
2016: Scientific Reports
Arminda Suli, Remy Pujol, Dale E Cunningham, Dale W Hailey, Andrew Prendergast, Edwin W Rubel, David W Raible
No abstract text is available yet for this article.
June 15, 2016: Development
Paul Werginz, Frank Rattay
OBJECTIVE: In spite of intense theoretical and experimental investigations on electrical nerve stimulation, the influence of reversed ion currents on network activity during extracellular stimulation has not been investigated so far. APPROACH: Here, the impact of calcium current reversal on neurotransmitter release during subretinal stimulation was analyzed with a computational multi-compartment model of a retinal bipolar cell (BC) that was coupled with a four-pool model for the exocytosis from its ribbon synapses...
August 2016: Journal of Neural Engineering
Caixia Lv, William J Stewart, Otar Akanyeti, Courtney Frederick, Jie Zhu, Joseph Santos-Sacchi, Lavinia Sheets, James C Liao, David Zenisek
Synaptic ribbons are structures made largely of the protein Ribeye that hold synaptic vesicles near release sites in non-spiking cells in some sensory systems. Here, we introduce frameshift mutations in the two zebrafish genes encoding for Ribeye and thus remove Ribeye protein from neuromast hair cells. Despite Ribeye depletion, vesicles collect around ribbon-like structures that lack electron density, which we term "ghost ribbons." Ghost ribbons are smaller in size but possess a similar number of smaller vesicles and are poorly localized to synapses and calcium channels...
June 21, 2016: Cell Reports
Lauren L Daniele, Farida Emran, Glenn P Lobo, Robert J Gaivin, Brian D Perkins
PURPOSE: Tail-anchored (TA) proteins contain a single hydrophobic domain at the C-terminus and are posttranslationally inserted into the ER membrane via the GET (guided entry of tail-anchored proteins) pathway. The role of the GET pathway in photoreceptors is unexplored. The goal of this study was to characterize the zebrafish pinball wizard mutant, which disrupts Wrb, a core component of the GET pathway. METHODS: Electroretinography, optokinetic response measurements (OKR), immunohistochemistry, and electron microscopy analyses were employed to assess ribbon synapse function, protein expression, and ultrastructure in 5-day-old zebrafish larvae...
June 1, 2016: Investigative Ophthalmology & Visual Science
Virginie Dinet, Giuseppe D Ciccotosto, Kimberley Delaunay, Céline Borras, Isabelle Ranchon-Cole, Corinne Kostic, Michèle Savoldelli, Mohamed El Sanharawi, Laurent Jonet, Caroline Pirou, Na An, Marc Abitbol, Yvan Arsenijevic, Francine Behar-Cohen, Roberto Cappai, Frédéric Mascarelli
BACKGROUND: Amyloid precursor protein knockout mice (APP-KO) have impaired differentiation of amacrine and horizontal cells. APP is part of a gene family and its paralogue amyloid precursor-like protein 2 (APLP2) has both shared as well as distinct expression patterns to APP, including in the retina. Given the impact of APP in the retina we investigated how APLP2 expression affected the retina using APLP2 knockout mice (APLP2-KO). RESULTS: Using histology, morphometric analysis with noninvasive imaging technique and electron microscopy, we showed that APLP2-KO retina displayed abnormal formation of the outer synaptic layer, accompanied with greatly impaired photoreceptor ribbon synapses in adults...
2016: Molecular Brain
Rodrigo Martinez-Monedero, Chang Liu, Catherine Weisz, Pankhuri Vyas, Paul Albert Fuchs, Elisabeth Glowatzki
Mechanosensory hair cells release glutamate at ribbon synapses to excite postsynaptic afferent neurons, via AMPA-type ionotropic glutamate receptors (AMPARs). However, type II afferent neurons contacting outer hair cells in the mammalian cochlea were thought to differ in this respect, failing to show GluA immunolabeling and with many "ribbonless" afferent contacts. Here it is shown that antibodies to the AMPAR subunit GluA2 labeled afferent contacts below inner and outer hair cells in the rat cochlea, and that synaptic currents in type II afferents had AMPAR-specific pharmacology...
March 2016: ENeuro
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