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Ribbon synapse

Randall J Harley, Joseph P Murdy, Zhirong Wang, Michael C Kelly, Tessa-Jonne F Ropp, SeHoon H Park, Patricia F Maness, Paul B Manis, Thomas M Coate
BACKGROUND: In the cochlea, auditory development depends on precise patterns of innervation by afferent and efferent nerve fibers, as well as a stereotyped arrangement of hair and supporting cells. NrCAM is a homophilic cell adhesion molecule that controls diverse aspects of nervous system development, but the function of NrCAM in cochlear development is not well understood. RESULTS: Throughout cochlear innervation, NrCAM is detectable on spiral ganglion neuron (SGN) afferent and olivocochlear efferent fibers, and on the membranes of developing hair and supporting cells...
March 14, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Judith S Kempfle, Kim Nguyen, Christine Hamadani, Nicholas Koen, Albert S Edge, Boris A Kashemirov, David H Jung, Charles E McKenna
Hearing loss affects more than two-thirds of the elderly population, and more than 17% of all adults in the U.S. Sensorineural hearing loss related to noise exposure or aging is associated with loss of inner ear sensory hair cells (HCs), cochlear spiral ganglion neurons (SGNs), and ribbon synapses between HCs and SGNs, stimulating intense interest in therapies to regenerate synaptic function. 7,8-Dihydroxyflavone (DHF) is a selective and potent agonist of tropomyosin receptor kinase B (TrkB) and protects the neuron from apoptosis...
February 27, 2018: Bioconjugate Chemistry
Carmen Haro, Mary Luz Uribe, Cristina Quereda, Jesús Cruces, José Martín-Nieto
Purpose: Dystroglycanopathies are a heterogeneous group of recessive neuromuscular dystrophies that affect the muscle, brain and retina, and are caused by deficiencies in the O-glycosylation of α-dystroglycan. This post-translational modification is essential for the formation and maintenance of ribbon synapses in the retina. Fukutin and fukutin-related protein (FKRP) are two glycosyltransferases whose deficiency is associated with severe dystroglycanopathies. These enzymes carry out in vitro the addition of a tandem ribitol 5-phosphate moiety to the so-called core M3 phosphotrisaccharide of α-dystroglycan...
2018: Molecular Vision
Pankaj Singh, Chung-Yuen Hui
Synaptic vesicle fusion is a crucial step in the neurotransmission process. Neurotransmitter-filled vesicles are pre-docked at the synapse by the mediation of ribbon structures and SNARE proteins at the ribbon synapses. An electrical impulse triggers the fusion process of pre-docked vesicles, leading to the formation of a fusion pore and subsequently resulting in the release of neurotransmitter into the synaptic cleft. In this study, a continuum model of lipid membrane along with lubrication theory is used to determine the traverse time of the synaptic vesicle under the influence of hydrodynamic forces...
January 2018: Journal of the Royal Society, Interface
Corinne L Fairchild, Keiko Hino, Jisoo S Han, Adam M Miltner, Gabriel Peinado Allina, Caileigh E Brown, Marie E Burns, Anna La Torre, Sergi Simo
The laminated structure of the retina is fundamental for the organization of the synaptic circuitry that translates light input into patterns of action potentials. However, the molecular mechanisms underlying cell migration and layering of the retina are poorly understood. Here, we show that RBX2, a core component of the E3 ubiquitin ligase CRL5, is essential for retinal layering and function. RBX2 regulates the final cell position of rod bipolar cells, cone photoreceptors, and Muller glia. Our data indicate that sustained Reelin/DAB1 signaling, triggered by depletion of RBX2 or SOCS7 -a CRL5 substrate adaptor known to recruit DAB1- causes rod bipolar cell misposition...
January 18, 2018: Development
Lars Becker, Michael E Schnee, Mamiko Niwa, Willy Sun, Stephan Maxeiner, Sara Talaei, Bechara Kachar, Mark A Rutherford, Anthony J Ricci
The ribbon is the structural hallmark of cochlear inner hair cell (IHC) afferent synapses, yet its role in information transfer to spiral ganglion neurons (SGNs) remains unclear. We investigated the ribbon's contribution to IHC synapse formation and function using KO mice lacking RIBEYE. Despite loss of the entire ribbon structure, synapses retained their spatiotemporal development and KO mice had a mild hearing deficit. IHCs of KO had fewer synaptic vesicles and reduced exocytosis in response to brief depolarization; a high stimulus level rescued exocytosis in KO...
January 12, 2018: ELife
Philippe Jean, David Lopez de la Morena, Susann Michanski, Lina María Jaime Tobón, Rituparna Chakrabarti, Maria Magdalena Picher, Jakob Neef, SangYong Jung, Mehmet Gültas, Stephan Maxeiner, Andreas Neef, Carolin Wichmann, Nicola Strenzke, Chad Grabner, Tobias Moser
We studied the role of the synaptic ribbon for sound encoding at the synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in mice lacking RIBEYE (RBEKO/KO). Electron and immunofluorescence microscopy revealed a lack of synaptic ribbons and an assembly of several small active zones (AZs) at each synaptic contact. Spontaneous and sound-evoked firing rates of SGNs and their compound action potential were reduced, indicating impaired transmission at ribbonless IHC-SGN synapses. The temporal precision of sound encoding was impaired and the recovery of SGN-firing from adaptation indicated slowed synaptic vesicle (SV) replenishment...
January 12, 2018: ELife
Liheng Shi, Janet Ya-An Chang, Fei Yu, Michael L Ko, Gladys Y-P Ko
L-type voltage-gated calcium channels (LTCCs) regulate tonic neurotransmitter release from sensory neurons including retinal photoreceptors. There are three types of LTCCs (Cav1.2, Cav1.3, and Cav1.4) expressed in the retina. While Cav1.2 is expressed in all retinal cells including the Müller glia and neurons, Cav1.3 and Cav1.4 are expressed in the retinal neurons with Cav1.4 exclusively expressed in the photoreceptor synaptic terminals. Mutations in the gene encoding Cav1.4 cause incomplete X-linked congenital stationary night blindness in humans...
2017: Frontiers in Molecular Neuroscience
G Aleph Prieto, Carl W Cotman
Synapses are essential units for the flow of information in the brain. Over the last 70 years, synapses have been widely studied in multiple animal models including worms, fruit flies, and rodents. In comparison, the study of human synapses has evolved significantly slower, mainly because of technical limitations. However, three novel methods allowing the analysis of molecular, morphological, and functional properties of human synapses may expand our knowledge of the human brain. Here, we briefly describe these methods, and evaluate how the information provided by each unique approach may contribute to the functional and anatomical analysis of the synaptic component of human brain circuitries...
October 2017: Neural Regeneration Research
Stefanie Krinner, Tanvi Butola, SangYong Jung, Carolin Wichmann, Tobias Moser
Ribbon synapses of inner hair cells (IHCs) mediate high rates of synchronous exocytosis to indefatigably track the stimulating sound with sub-millisecond precision. The sophisticated molecular machinery of the inner hair cell active zone realizes this impressive performance by enabling a large number of synaptic voltage-gated CaV 1.3 Ca2+ -channels, their tight coupling to synaptic vesicles (SVs) and fast replenishment of fusion competent SVs. Here we studied the role of RIM-binding protein 2 (RIM-BP2)-a multidomain cytomatrix protein known to directly interact with Rab3 interacting molecules (RIMs), bassoon and CaV 1...
2017: Frontiers in Cellular Neuroscience
Tanvi Butola, Carolin Wichmann, Tobias Moser
Piccolo and Bassoon are the two largest cytomatrix of the active zone (CAZ) proteins involved in scaffolding and regulating neurotransmitter release at presynaptic active zones (AZs), but have long been discussed as being functionally redundant. We employed genetic manipulation to bring forth and segregate the role of Piccolo from that of Bassoon at central auditory synapses of the cochlear nucleus-the endbulbs of Held. These synapses specialize in high frequency synaptic transmission, ideally poised to reveal even subtle deficits in the regulation of neurotransmitter release upon molecular perturbation...
2017: Frontiers in Synaptic Neuroscience
Yoshihiko Tsukamoto, Naoko Omi
We confirmed the classification of 15 morphological types of mouse bipolar cells by serial section transmission electron microscopy and characterized each type by identifying chemical synapses and gap junctions at axon terminals. Although whether the previous type 5 cells consist of two or three types was uncertain, they are here clustered into three types based on the vertical distribution of axonal ribbons. Next, while two groups of rod bipolar (RB) cells, RB1, and RB2, were previously proposed, we clarify that a half of RB1 cells have the intermediate characteristics, suggesting that these two groups comprise a single RB type...
2017: Frontiers in Neuroanatomy
Nicolas Michalski, Juan D Goutman, Sarah Marie Auclair, Jacques Boutet de Monvel, Margot Tertrais, Alice Emptoz, Alexandre Parrin, Sylvie Nouaille, Marc Guillon, Martin Sachse, Danica Ciric, Amel Bahloul, Jean-Pierre Hardelin, Roger Bryan Sutton, Paul Avan, Shyam S Krishnakumar, James E Rothman, Didier Dulon, Saaid Safieddine, Christine Petit
Hearing relies on rapid, temporally precise, and sustained neurotransmitter release at the ribbon synapses of sensory cells, the inner hair cells (IHCs). This process requires otoferlin, a six C2 -domain, Ca2+ -binding transmembrane protein of synaptic vesicles. To decipher the role of otoferlin in the synaptic vesicle cycle, we produced knock-in mice ( Otof Ala515,Ala517/Ala515,Ala517 ) with lower Ca2+ -binding affinity of the C2 C domain. The IHC ribbon synapse structure, synaptic Ca2+ currents, and otoferlin distribution were unaffected in these mutant mice, but auditory brainstem response wave-I amplitude was reduced...
November 7, 2017: ELife
Rui Cai, Scott C Montgomery, Kaley A Graves, Donald M Caspary, Brandon C Cox
Age-related hearing loss is experienced by one-third of individuals aged 65 years and older and can be socially debilitating. Historically, there has been poor correlation between age-related threshold changes, loss of speech understanding, and loss of cochlear hair cells. We examined changes in ribbon synapse number at four different ages in Fisher Brown Norway rats, an extensively studied rat model of aging. In contrast to previous work in mice/Wistar rats, we found minimal ribbon synapse loss before 20 months, with significant differences in 24- and 28-month-old rats at 4 kHz...
October 9, 2017: Neurobiology of Aging
Adam J Peterson, Peter Heil
The initial neural encoding of acoustic information occurs by means of spikes in primary auditory afferents. Each mammalian primary auditory afferent (type-I auditory-nerve fiber; ANF) is associated with only one ribbon synapse in one receptor cell (inner hair cell; IHC). The properties of ANF spike trains therefore provide an indirect view of the operation of individual IHC synapses. We showed previously that a point process model of presynaptic vesicle pool depletion and deterministic exponential replenishment, combined with short postsynaptic neural refractoriness, accounts for the interspike interval (ISI) distributions, serial ISI correlations, and spike-count statistics of a population of cat-ANF spontaneous spike trains...
September 15, 2017: Hearing Research
Xiangyi Wen, Grant W Saltzgaber, Wallace B Thoreson
Accompanying sustained release in darkness, rod and cone photoreceptors exhibit rapid endocytosis of synaptic vesicles. Membrane capacitance measurements indicated that rapid endocytosis retrieves at least 70% of the exocytotic membrane increase. One mechanism for rapid endocytosis is kiss-and-run fusion where vesicles briefly contact the plasma membrane through a small fusion pore. Release can also occur by full-collapse in which vesicles merge completely with the plasma membrane. We assessed relative contributions of full-collapse and kiss-and-run in salamander photoreceptors using optical techniques to measure endocytosis and exocytosis of large vs...
2017: Frontiers in Cellular Neuroscience
Le Yang, DaiShi Chen, TengFei Qu, TongHui Ding, AiHui Yan, Pinggui Gong, Yunyi Liu, Junjun Zhang, ShuSheng Gong, ShiMing Yang, Hong Peng, Ke Liu
OBJECTIVE: To investigate whether there are more quantitative pre-synaptic ribbons formed in the cochlear region corresponding to middle-frequency in cochlea of mice. METHODS: Counts of pre-synaptic ribbons were performed using immunostaining and laser confocal microscopy. Hearing thresholds and function of ribbon synapses were estimated by auditory brain response (ABR) and compound action potential (CAP). Cochlear mapping has been achieved to match the frequencies and corresponding regions along the cochlear spiral...
September 26, 2017: Acta Oto-laryngologica
Espen Hartveit, Bas-Jan Zandt, Eirik Madsen, Áurea Castilho, Svein Harald Mørkve, Margaret Lin Veruki
In chemical synapses, neurotransmitter molecules released from presynaptic vesicles activate populations of postsynaptic receptors that vary in functional properties depending on their subunit composition. Differential expression and localization of specific receptor subunits are thought to play fundamental roles in signal processing, but our understanding of how that expression is adapted to the signal processing in individual synapses and microcircuits is limited. At ribbon synapses, glutamate release is independent of action potentials and characterized by a high and rapidly changing rate of release...
September 21, 2017: Brain Structure & Function
Hideo Hoshi, Fumi Sato
The vertebrate retina has about 30 subtypes of ganglion cells. Each ganglion cell receives synaptic inputs from specific types of bipolar and amacrine cells ramifying at the same depth of the inner plexiform layer (IPL), each of which is thought to process a specific aspect of visual information. Here, we identified one type of displaced ganglion cell in the goldfish retina which had a large and elongated dendritic field. As a population, all of these ganglion cells were oriented in the horizontal axis and perpendicular to the dorsal-ventral axis of the goldfish eye in the central part of retina...
February 1, 2018: Journal of Comparative Neurology
Robert Fettiplace
Sound pressure fluctuations striking the ear are conveyed to the cochlea, where they vibrate the basilar membrane on which sit hair cells, the mechanoreceptors of the inner ear. Recordings of hair cell electrical responses have shown that they transduce sound via submicrometer deflections of their hair bundles, which are arrays of interconnected stereocilia containing the mechanoelectrical transducer (MET) channels. MET channels are activated by tension in extracellular tip links bridging adjacent stereocilia, and they can respond within microseconds to nanometer displacements of the bundle, facilitated by multiple processes of Ca2+-dependent adaptation...
September 12, 2017: Comprehensive Physiology
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