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https://www.readbyqxmd.com/read/28438658/antioxidants-reduce-neurodegeneration-and-accumulation-of-pathologic-tau-proteins-in-the-auditory-system-after-blast-exposure
#1
Xiaoping Du, Matthew B West, Qunfeng Cai, Weihua Cheng, Donald L Ewert, Wei Li, Robert A Floyd, Richard D Kopke
Cochlear neurodegeneration commonly accompanies hair cell loss resulting from aging, ototoxicity, or exposures to intense noise or blast overpressures. However, the precise pathophysiological mechanisms that drive this degenerative response have not been fully elucidated. Our laboratory previously demonstrated that non-transgenic rats exposed to blast overpressures exhibited marked somatic accumulation of neurotoxic variants of the microtubule-associated protein, Tau, in the hippocampus. In the present study, we extended these analyses to examine neurodegeneration and pathologic Tau accumulation in the auditory system in response to blast exposure and evaluated the potential therapeutic efficacy of antioxidants on short-circuiting this pathological process...
April 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28378516/how-do-horizontal-cells-talk-to-cone-photoreceptors-different-levels-of-complexity-at-the-cone-horizontal-cell-synapse
#2
Camille A Chapot, Thomas Euler, Timm Schubert
The first synapse of the retina plays a fundamental role in the visual system. Due to its importance, it is critical that it encodes information from the outside world with the greatest accuracy and precision possible. Cone photoreceptor axon terminals contain many individual synaptic sites, each represented by a presynaptic structure called a "ribbon". These synapses are both highly sophisticated and conserved. Each ribbon relays the light signal to one ON cone bipolar cell and several OFF cone bipolar cells, while two dendritic processes from a GABAergic interneuron, the horizontal cell, modulate the cone output via parallel feedback mechanisms...
April 5, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28363980/a-presynaptic-group-iii-mglur-recruits-g%C3%AE-%C3%AE-snare-interactions-to-inhibit-synaptic-transmission-by-cone-photoreceptors-in-the-vertebrate-retina
#3
Matthew J Van Hook, Norbert Babai, Zack Zurawski, Yun Young Yim, Heidi E Hamm, Wallace B Thoreson
G-protein βγ subunits (Gβγ) interact with presynaptic proteins and regulate neurotransmitter release downstream of Ca(2+) influx. To accomplish their roles in sensory signaling, photoreceptor synapses employ specialized presynaptic proteins that support neurotransmission at active zone structures known as ribbons. While several G-protein coupled receptors (GPCRs) influence synaptic transmission at ribbon synapses of cones and other retinal neurons, it is unknown whether Gβγ contributes to these effects...
March 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28346141/insights-into-electrosensory-organ-development-physiology-and-evolution-from-a-lateral-line-enriched-transcriptome
#4
Melinda S Modrell, Mike Lyne, Adrian R Carr, Harold H Zakon, David Buckley, Alexander S Campbell, Marcus C Davis, Gos Micklem, Clare Vh Baker
The anamniote lateral line system, comprising mechanosensory neuromasts and electrosensory ampullary organs, is a useful model for investigating the developmental and evolutionary diversification of different organs and cell types. Zebrafish neuromast development is increasingly well understood, but neither zebrafish nor Xenopus is electroreceptive and our molecular understanding of ampullary organ development is rudimentary. We have used RNA-seq to generate a lateral line-enriched gene-set from late-larval paddlefish (Polyodon spathula)...
March 27, 2017: ELife
https://www.readbyqxmd.com/read/28334377/lrit3-differentially-affects-connectivity-and-synaptic-transmission-of-cones-to-on-and-off-bipolar-cells
#5
Marion Neuillé, Yan Cao, Romain Caplette, Debbie Guerrero-Given, Connon Thomas, Naomi Kamasawa, José-Alain Sahel, Christian P Hamel, Isabelle Audo, Serge Picaud, Kirill A Martemyanov, Christina Zeitz
Purpose: Mutations in LRIT3 lead to complete congenital stationary night blindness (cCSNB). Using a cCSNB mouse model lacking Lrit3 (nob6), we recently have shown that LRIT3 has a role in the correct localization of TRPM1 (transient receptor potential melastatin 1) to the dendritic tips of ON-bipolar cells (BCs), contacting both rod and cone photoreceptors. Furthermore, postsynaptic clustering of other mGluR6 cascade components is selectively eliminated at the dendritic tips of cone ON-BCs...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28332931/unitary-ototoxic-gentamicin-exposure-may-not-disrupt-the-function-of-cochlear-outer-hair-cells-in-mice
#6
Ning Zhao, XuHui Tai, LiJie Zhai, Lin Shi, DaiShi Chen, Bo Yang, Fei Ji, Kun Hou, ShiMing Yang, ShuSheng Gong, Ke Liu
BACKGROUND: Previous study showed that mild ototoxic exposure could induce a reversible hearing impairment, and the loss and secondary incomplete recovery of cochlear ribbon synapses could be responsible for the hearing loss. However, it remains unclear whether cochlear outer hair cells' (OHCs) functions are affected. OBJECTIVE: To verify whether the function of OHCs are also affected significantly after the ototoxic exposure. METHODS: Mice were injected intraperitoneally with 100 mg/kg concentration of gentamicin daily for 14 days...
March 23, 2017: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/28322827/structural-divergence-of-essential-triad-ribbon-synapse-proteins-among-placental-mammals-implications-for-preclinical-trials-in-photoreceptor-transplantation-therapy
#7
Christopher R J Laver, Joanne A Matsubara
As photoreceptor transplantation rapidly moves closer to the clinic, verifying graft efficacy in animal models may have unforeseen xenogeneic barriers. Although photoreceptor transplants have most convincingly exhibited functional synaptogenesis in conspecific studies, such evidence (while ruling out false-positives due to: viral graft labeling, fusion/cytosolic transfer, or neuroprotection) has not yet been shown for discordant xenografts. From this, a fundamental question should be raised: is useful xenosynaptogenesis likely between human photoreceptors and mouse retina? The triad ribbon synapse (TRS) that would normally form is unique and contains trans-synaptic proteins essential to its formation and function...
March 18, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28298303/ampa-receptor-mediated-rapid-epscs-in-vestibular-calyx-afferents
#8
Matthew Edward Kirk, Frances L Meredith, Tim A Benke, Katherine J Rennie
In the vestibular periphery neurotransmission between hair cells and primary afferent nerves occurs via specialized ribbon synapses. Type I vestibular hair cells (HCI) make synaptic contacts with calyx terminals, which enclose most of the HCI basolateral surface. To probe synaptic transmission, whole cell patch clamp recordings were made from calyx afferent terminals isolated together with their mature HCI from gerbil crista. Neurotransmitter release was measured as excitatory postsynaptic currents (EPSCs) in voltage clamp...
March 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28262416/the-auxiliary-calcium-channel-subunit-%C3%AE-2%C3%AE-4-is-required-for-axonal-elaboration-synaptic-transmission-and-wiring-of-rod-photoreceptors
#9
Yuchen Wang, Katherine E Fehlhaber, Ignacio Sarria, Yan Cao, Norianne T Ingram, Debbie Guerrero-Given, Ben Throesch, Kristin Baldwin, Naomi Kamasawa, Toshihisa Ohtsuka, Alapakkam P Sampath, Kirill A Martemyanov
Neural circuit wiring relies on selective synapse formation whereby a presynaptic release apparatus is matched with its cognate postsynaptic machinery. At metabotropic synapses, the molecular mechanisms underlying this process are poorly understood. In the mammalian retina, rod photoreceptors form selective contacts with rod ON-bipolar cells by aligning the presynaptic voltage-gated Ca(2+) channel directing glutamate release (CaV1.4) with postsynaptic mGluR6 receptors. We show this coordination requires an extracellular protein, α2δ4, which complexes with CaV1...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28228581/spaceflight-induced-synaptic-modifications-within-hair-cells-of-the-mammalian-utricle
#10
David R Sultemeier, Kristel R Choy, Felix E Schweizer, Larry F Hoffman
Exposure to the microgravity conditions of spaceflight alleviates the load normally imposed by the Earth's gravitational field upon the inner ear utricular epithelia. Previous ultrastructural investigations showed that spaceflight induced an increase in synapse density within hair cells of the rat utricle. However, the utricle exhibits broad physiologic heterogeneity across different epithelial regions, and it is unknown whether capabilities for synaptic plasticity generalize to hair cells across its topography...
February 22, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28209381/an-easy-fast-and-low-tech-equipment-requiring-alternative-method-to-optimize-immunolabelling-conditions-for-pre-embedding-immunogold-electron-microscopy-and-to-correlate-light-and-electron-microscopical-immunogold-labelling-results
#11
Shweta Suiwal, Gabriele Kiefer, Frank Schmitz, Karin Schwarz
Correlating light microscopic immunolabelling results with electron microscopic data is of great interest in many fields of biomedical research but typically requires very specialized, expensive equipment and complex procedures which are not available in most labs. In this technical study, we describe an easy and "low-tech"-equipment-requiring pre-embedding immunolabelling approach that allows correlation of light microscopical immunolabelling results with electron microscopic (EM) data as demonstrated by the example of immunolabelled synaptic ribbons from retinal rod photoreceptor synapses...
February 13, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28202712/ribeye-b-domain-binds-to-lipid-components-of-synaptic-vesicles-in-an-nad-h-dependent-redox-sensitive-manner
#12
Karin Schwarz, Frank Schmitz
Synaptic ribbons are needed for fast and continuous exocytosis in ribbon synapses. RIBEYE is a main protein component of synaptic ribbons and is necessary to build the synaptic ribbon. RIBEYE consists of a unique A-domain and a carboxyterminal B-domain, which binds NAD(H). Within the presynaptic terminal, the synaptic ribbons are in physical contact with large numbers of synaptic vesicle (SV)s. How this physical contact between ribbons and synaptic vesicles is established at a molecular level is not well understood...
March 20, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28193694/different-cav1-3-channel-isoforms-control-distinct-components-of-the-synaptic-vesicle-cycle-in-auditory-inner-hair-cells
#13
Philippe Fy Vincent, Yohan Bouleau, Gilles Charpentier, Alice Emptoz, Saaid Safieddine, Christine Petit, Didier Dulon
The mechanisms orchestrating transient and sustained exocytosis in auditory inner hair cells (IHCs) remain largely unknown. These exocytotic responses are believed to mobilize sequentially a readily releasable pool of vesicles (RRP) underneath the synaptic ribbons and a slowly releasable pool of vesicles (SRP) at farther distance from them. They are both governed by Cav1.3 channels and require otoferlin as Ca(2+) sensor but whether they use the same Cav1.3 isoforms is still unknown. Using whole cell patch clamp recordings in post-hearing mice, we show that only a proportion (∼25 %) of the total Ca(2+) current in IHCs, displaying fast inactivation and resistance to 20 μM nifedipine, a L-type Ca(2+) channel blocker, is sufficient to trigger RRP but not SRP exocytosis...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28183797/ca-2-binding-protein-2-inhibits-ca-2-channel-inactivation-in-mouse-inner-hair-cells
#14
Maria Magdalena Picher, Anna Gehrt, Sandra Meese, Aleksandra Ivanovic, Friederike Predoehl, SangYong Jung, Isabelle Schrauwen, Alberto Giulio Dragonetti, Roberto Colombo, Guy Van Camp, Nicola Strenzke, Tobias Moser
Ca(2+)-binding protein 2 (CaBP2) inhibits the inactivation of heterologously expressed voltage-gated Ca(2+) channels of type 1.3 (CaV1.3) and is defective in human autosomal-recessive deafness 93 (DFNB93). Here, we report a newly identified mutation in CABP2 that causes a moderate hearing impairment likely via nonsense-mediated decay of CABP2-mRNA. To study the mechanism of hearing impairment resulting from CABP2 loss of function, we disrupted Cabp2 in mice (Cabp2(LacZ/LacZ) ). CaBP2 was expressed by cochlear hair cells, preferentially in inner hair cells (IHCs), and was lacking from the postsynaptic spiral ganglion neurons (SGNs)...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28160289/melanopsin-expressing-human-retinal-ganglion-cells-subtypes-distribution-and-intraretinal-connectivity
#15
Jens Hannibal, Anders Tolstrup Christiansen, Steffen Heegaard, Jan Fahrenkrug, Jens Folke Kiilgaard
Intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin belong to a heterogenic population of RGCs which regulate the circadian clock, masking behavior, melatonin suppression, the pupillary light reflex, and sleep/wake cycles. The different functions seem to be associated to different subtypes of melanopsin cells. In rodents, subtype classification has associated subtypes to function. In primate and human retina such classification has so far, not been applied. In the present study using antibodies against N- and C-terminal parts of human melanopsin, confocal microscopy and 3D reconstruction of melanopsin immunoreactive (-ir) RGCs, we applied the criteria used in mouse on human melanopsin-ir RGCs...
June 1, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28154149/the-coupling-between-ca-2-channels-and-the-exocytotic-ca-2-sensor-at-hair-cell-ribbon-synapses-varies-tonotopically-along-the-mature-cochlea
#16
Stuart L Johnson, Jennifer Olt, Soyoun Cho, Henrique von Gersdorff, Walter Marcotti
The cochlea processes auditory signals over a wide range of frequencies and intensities. However, the transfer characteristics at hair cell ribbon synapses are still poorly understood at different frequency locations along the cochlea. Using recordings from mature gerbils, we report here a surprisingly strong block of exocytosis by the slow Ca(2+) buffer EGTA (10 mM) in basal hair cells tuned to high frequencies (∼30 kHz). In addition, using recordings from gerbil, mouse, and bullfrog auditory organs, we find that the spatial coupling between Ca(2+) influx and exocytosis changes from nanodomain in low-frequency tuned hair cells (∼<2 kHz) to progressively more microdomain in high-frequency cells (∼>2 kHz)...
March 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28089576/conditional-deletion-of-pejvakin-in-adult-outer-hair-cells-causes-progressive-hearing-loss-in-mice
#17
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...
March 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28074469/development-of-cone-photoreceptors-and-their-synapses-in-the-human-and-monkey-fovea
#18
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
#19
Anna Fasoli, James Dang, Jeffrey S Johnson, Aaron H Gouw, 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 that 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
#20
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 h to induce cochlear injury and hearing loss...
December 26, 2016: Hearing Research
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