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https://www.readbyqxmd.com/read/28089576/conditional-deletion-of-pejvakin-in-adult-outer-hair-cells-causes-progressive-hearing-loss-in-mice
#1
Suzan L Harris, Marcin Kazmierczak, Tina Pangršič, Prahar Shah, Nadiya Chuchvara, Alonso Barrantes-Freer, Tobias Moser, Martin Schwander
Mutations in the Pejvakin (Pjvk) gene cause autosomal recessive hearing loss DFNB59 with audiological features of auditory neuropathy spectrum disorder (ANSD) or cochlear dysfunction. The precise mechanisms underlying the variable clinical phenotypes of DFNB59 remain unclear. Here, we demonstrate that mice with conditional ablation of the Pjvk gene in all sensory hair cells or only in outer hair cells (OHCs) show similar auditory phenotypes with early-onset profound hearing loss. By contrast, loss of Pjvk in adult OHCs causes a slowly progressive hearing loss associated with OHC degeneration and delayed loss of inner hair cells (IHCs), indicating a primary role for pejvakin in regulating OHC function and survival...
January 9, 2017: Neuroscience
https://www.readbyqxmd.com/read/28074469/development-of-cone-photoreceptors-and-their-synapses-in-the-human-and-monkey-fovea
#2
Anita Hendrickson, Chi Zhang
During retinal development, ribbon synapse assembly in the photoreceptors is a crucial step involving numerous molecules. While the developmental sequence of plexiform layers in human retina has been characterized, the molecular steps of synaptogenesis remain largely unknown. In the present study, we focused on the central rod-free region of primate retina, the fovea, to specifically investigate the development of cone photoreceptor ribbon synapses. Immunocytochemistry and electron microscopy were utilized to track the expression of photoreceptor transduction proteins and ribbon and synaptic markers in fetal human and Macaca retina...
January 11, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28035673/somatic-and-neuritic-spines-on-tyrosine-hydroxylase-immunopositive-cells-of-rat-retina
#3
Anna Fasoli, James Dang, Aaron H Gouw, Jeffrey S Johnson, Alex Fogli Iseppe, Andrew T Ishida
Dopamine- and tyrosine hydroxylase-immunopositive cells (TH cells) modulate visually driven signals as they flow through retinal photoreceptor, bipolar, and ganglion cells. Previous studies suggested that TH cells release dopamine from varicose axons arborizing in the inner and outer plexiform layers after glutamatergic synapses depolarize TH cell dendrites in the inner plexiform layer and these depolarizations propagate to the varicosities. Although it has been proposed that these excitatory synapses are formed onto appendages resembling dendritic spines, spines have not been found on TH cells of most species examined to date or on TH cell somata which release dopamine when exposed to glutamate receptor agonists...
December 30, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28034618/adenosine-receptors-regulate-susceptibility-to-noise-induced-neural-injury-in-the-mouse-cochlea-and-hearing-loss
#4
Srdjan M Vlajkovic, Kaushi Ambepitiya, Meagan Barclay, Detlev Boison, Gary D Housley, Peter R Thorne
Our previous studies have shown that the stimulation of A1 adenosine receptors in the inner ear can mitigate the loss of sensory hair cells and hearing loss caused by exposure to traumatic noise. Here, we focus on the role of adenosine receptors (AR) in the development of noise-induced neural injury in the cochlea using A1AR and A2AAR null mice (A1AR(-/-) and A2AAR(-/-)). Wildtype (WT) and AR deficient mice were exposed to octave band noise (8-16 kHz, 100 dB SPL) for 2 hours to induce cochlear injury and hearing loss...
December 26, 2016: Hearing Research
https://www.readbyqxmd.com/read/27833534/on-bipolar-cells-in-macaque-retina-type-specific-synaptic-connectivity-with-special-reference-to-off-counterparts
#5
Yoshihiko Tsukamoto, Naoko Omi
To date, 12 macaque bipolar cell types have been described. This list includes all morphology types first outlined by Polyak (1941) using the Golgi method in the primate retina and subsequently identified by other researchers using electron microscopy (EM) combined with the Golgi method, serial section transmission EM (SSTEM), and immunohistochemical imaging. We used SSTEM for the rod-dense perifoveal area of macaque retina, reconfirmed ON (cone) bipolar cells to be classified as invaginating midget bipolar (IMB), diffuse bipolar (DB)4, DB5, DB6, giant bipolar (GB), and blue bipolar (BB) types, and clarified their type-specific connectivity...
2016: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/27822497/lack-of-cabp1-caldendrin-or-cabp2-leads-to-altered-ganglion-cell-responses
#6
Raunak Sinha, Amy Lee, Fred Rieke, Françoise Haeseleer
Calcium-binding proteins (CaBPs) form a subfamily of calmodulin-like proteins that were cloned from the retina. CaBP4 and CaBP5 have been shown to be important for normal visual function. Although CaBP1/caldendrin and CaBP2 have been shown to modulate various targets in vitro, it is not known whether they contribute to the transmission of light responses through the retina. Therefore, we generated mice that lack CaBP2 or CaBP1/caldendrin (Cabp2(-/-) and Cabp1(-/-) ) to test whether these CaBPs are essential for normal retinal function...
September 2016: ENeuro
https://www.readbyqxmd.com/read/27798183/%C3%AE-2%C3%AE-2-controls-the-function-and-trans-synaptic-coupling-of-cav1-3-channels-in-mouse-inner-hair-cells-and-is-essential-for-normal-hearing
#7
Barbara Fell, Stephanie Eckrich, Kerstin Blum, Tobias Eckrich, Dietmar Hecker, Gerald J Obermair, Stefan Münkner, Veit Flockerzi, Bernhard Schick, Jutta Engel
: The auxiliary subunit α2δ2 modulates the abundance and function of voltage-gated calcium channels. Here we show that α2δ2 mRNA is expressed in neonatal and mature hair cells. A functional α2δ2-null mouse, the ducky mouse (du), showed elevated auditory brainstem response click and frequency-dependent hearing thresholds. Otoacoustic emissions were not impaired pointing to normal outer hair cell function. Peak Ca(2+) and Ba(2+) currents of mature du/du inner hair cells (IHCs) were reduced by 30-40%, respectively, and gating properties, such as the voltage of half-maximum activation and voltage sensitivity, were altered, indicating that Cav1...
October 26, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27793584/effects-of-long-term-non-traumatic-noise-exposure-on-the-adult-central-auditory-system-hearing-problems-without-hearing-loss
#8
REVIEW
Jos J Eggermont
It is known that hearing loss induces plastic changes in the brain, causing loudness recruitment and hyperacusis, increased spontaneous firing rates and neural synchrony, reorganizations of the cortical tonotopic maps, and tinnitus. Much less in known about the central effects of exposure to sounds that cause a temporary hearing loss, affect the ribbon synapses in the inner hair cells, and cause a loss of high-threshold auditory nerve fibers. In contrast there is a wealth of information about central effects of long-duration sound exposures at levels ≤ 80 dB SPL that do not even cause a temporary hearing loss...
October 25, 2016: Hearing Research
https://www.readbyqxmd.com/read/27635230/new-insights-into-cochlear-sound-encoding
#9
REVIEW
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
https://www.readbyqxmd.com/read/27581463/selective-vulnerability-of-specific-retinal-ganglion-cell-types-and-synapses-after-transient-ocular-hypertension
#10
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
https://www.readbyqxmd.com/read/27569111/behavioral-auditory-thresholds-and-loss-of-ribbon-synapses-at-inner-hair-cells-in-aged-gerbils
#11
Otto Gleich, Philipp Semmler, Jürgen Strutz
The potential contribution of auditory synaptopathy to age dependent hearing loss was studied in groups of young and old gerbils. The analysis of the number of inner hair cell ribbon synapses in aged gerbils (37.9±3.3months of age) revealed only a relatively small (11-17%) loss in the basal two thirds of the cochlea, while a more pronounced reduction was identified towards the apex (almost 40%) when compared to a group of young gerbils (9.5±3.2months of age). Mean threshold elevation in the old gerbils was around 25dB at 2 and 10kHz...
November 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/27542193/physical-determinants-of-vesicle-mobility-and-supply-at-a-central-synapse
#12
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
https://www.readbyqxmd.com/read/27466786/spike-timing-in-auditory-nerve-fibers-during-spontaneous-activity-and-phase-locking
#13
Peter Heil, Adam J Peterson
In vertebrates, all acoustic information transmitted from the inner ear to the central auditory system is relayed by primary auditory afferents (auditory-nerve fibers; ANFs). These neurons are also the most peripheral elements to use action potentials (spikes) to encode the acoustic information. Here, we review what is known about the spiking of ANFs during spontaneous activity, when spike timing might be regarded as largely random, and during stimulation by low-frequency sounds, when spikes are phase locked to the stimulus waveform, a phenomenon generally considered a hallmark of temporal precision and speed in the auditory system...
July 28, 2016: Synapse
https://www.readbyqxmd.com/read/27458190/tryptophan-rich-basic-protein-wrb-mediates-insertion-of-the-tail-anchored-protein-otoferlin-and-is-required-for-hair-cell-exocytosis-and-hearing
#14
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...
December 1, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27426514/glutamatergic-monopolar-interneurons-provide-a-novel-pathway-of-excitation-in-the-mouse-retina
#15
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
https://www.readbyqxmd.com/read/27375437/non-image-forming-light-detection-by-melanopsin-rhodopsin-and-long-middlewave-l-w-cone-opsin-in-the-subterranean-blind-mole-rat-spalax-ehrenbergi-immunohistochemical-characterization-distribution-and-connectivity
#16
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
https://www.readbyqxmd.com/read/27335398/functional-roles-of-complexin3-and-complexin4-at-mouse-photoreceptor-ribbon-synapses
#17
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
https://www.readbyqxmd.com/read/27321892/dual-color-sted-microscopy-reveals-a-sandwich-structure-of-bassoon-and-piccolo-in-active-zones-of-adult-and-aged-mice
#18
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
https://www.readbyqxmd.com/read/27296730/the-impact-of-calcium-current-reversal-on-neurotransmitter-release-in-the-electrically-stimulated-retina
#19
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
https://www.readbyqxmd.com/read/27292637/synaptic-ribbons-require-ribeye-for-electron-density-proper-synaptic-localization-and-recruitment-of-calcium-channels
#20
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
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