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Available from: Dietmar Riedel, Aug 31, 2015
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    • "Bassoon was also shown to regulate RRP size, Ca 2+ current amplitude, and occupancy of release sites at the ribbon synapse of the inner hair cell (Frank et al., 2010). These latter findings may be limited to ribbon synapses, since they seem to correlate with the detachment of the ribbon from the AZ (Frank et al., 2010; Jing et al., 2013). In our study, we could not detect any changes in RRP size or calcium current amplitude , but we noticed a slight, non-significant reduction in the replenishment rate during high-frequency trains. "
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    ABSTRACT: Mover, a member of the exquisitely small group of vertebrate-specific presynaptic proteins, has been discovered as an interaction partner of the scaffolding protein Bassoon, yet its function has not been elucidated. We used adeno-associated virus (AAV)-mediated shRNA expression to knock down Mover in the calyx of Held in vivo. Although spontaneous synaptic transmission remained unaffected, we found a strong increase of the evoked EPSC amplitude. The size of the readily releasable pool was unaltered, but short-term depression was accelerated and enhanced, consistent with an increase in release probability after Mover knockdown. This increase in release probability was not caused by alterations in Ca(2+) influx but rather by a higher Ca(2+) sensitivity of the release machinery, as demonstrated by presynaptic Ca(2+) uncaging. We therefore conclude that Mover expression in certain subsets of synapses negatively regulates synaptic release probability, constituting a novel mechanism to tune synaptic transmission. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neuron 07/2015; DOI:10.1016/j.neuron.2015.07.001 · 15.98 Impact Factor
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    • " with 60 nm lateral resolution ( Hell and Wichmann , 1994 ; Nägerl et al . , 2008 ; Liu et al . , 2011 ; Urban et al . , 2011 ) . STED microscopy was instrumental in detecting a disorganization of Ca 2+ channel punctae in inner ear hair cells lacking Bassoon , demonstrating its role in organizing the precise localization of Ca 2+ channels at AZs ( Frank et al . , 2010 ) . Detection efficiency in immuno - EM is limited by many factors , including embedding material , epitope preservation , lack of specific antibodies and difficulty achieving adequate tissue penetration . Correlative light and EM microscopy ( CLEM ) has begun to address these issues by combining the advantages of EM with those of fluor"
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    ABSTRACT: Synapses are the fundamental functional units of neural circuits, and their dysregulation has been implicated in diverse neurological disorders. At presynaptic terminals, neurotransmitter-filled synaptic vesicles are released in response to calcium influx through voltage-gated calcium channels activated by the arrival of an action potential. Decades of electrophysiological, biochemical, and genetic studies have contributed to a growing understanding of presynaptic biology. Imaging studies are yielding new insights into how synapses are organized to carry out their critical functions. The development of techniques for rapid immobilization and preservation of neuronal tissues for electron microscopy has led to a new renaissance in ultrastructural imaging that is rapidly advancing our understanding of synapse structure and function.
    Frontiers in Cellular Neuroscience 05/2015; 9(196). DOI:10.3389/fncel.2015.00196 · 4.18 Impact Factor
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    • "Ca V 1.4 immunofluorescence intensity was measured as the integral of the pixel values under the two-dimensional Gaussian fitted to the individual ribbon-associated Ca V 1.4 immunofluorescence after subtraction of the background (estimated by fitting a linear function to the region outside of the 2D Gaussian and subsequently subtracting this function from the entire image) as done previously in hair cells (Frank et al., 2010 "
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    ABSTRACT: How size and shape of presynaptic active zones are regulated at the molecular level has remained elusive. Here we provide insight from studying rod photoreceptor ribbon-type active zones after disruption of CAST/ERC2, one of the cytomatrix of the active zone (CAZ) proteins. Rod photoreceptors were present in normal numbers, and the a-wave of the electroretinogram (ERG)--reflecting their physiological population response--was unchanged in CAST knock-out (CAST(-/-)) mice. Using immunofluorescence and electron microscopy, we found that the size of the rod presynaptic active zones, their Ca(2+) channel complement, and the extension of the outer plexiform layer were diminished. Moreover, we observed sprouting of horizontal and bipolar cells toward the outer nuclear layer indicating impaired rod transmitter release. However, rod synapses of CAST(-/-) mice, unlike in mouse mutants for the CAZ protein Bassoon, displayed anchored ribbons, normal vesicle densities, clustered Ca(2+) channels, and essentially normal molecular organization. The reduction of the rod active zone size went along with diminished amplitudes of the b-wave in scotopic ERGs. Assuming, based on the otherwise intact synaptic structure, an unaltered function of the remaining release apparatus, we take our finding to suggest a scaling of release rate with the size of the active zone. Multielectrode-array recordings of retinal ganglion cells showed decreased contrast sensitivity. This was also observed by optometry, which, moreover, revealed reduced visual acuity. We conclude that CAST supports large active zone size and high rates of transmission at rod ribbon synapses, which are required for normal vision.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 08/2012; 32(35):12192-203. DOI:10.1523/JNEUROSCI.0752-12.2012 · 6.75 Impact Factor
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