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Available from: Dietmar Riedel, Oct 07, 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; 87(3). DOI:10.1016/j.neuron.2015.07.001 · 15.05 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 · 4.29 Impact Factor
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    • "Moreover, dynamic reorganizations of Brp accompany rapid AZ strengthening and increase the number of release sites during homeostatic synaptic plasticity (Weyhersmüller et al., 2011). Similarly, studies at mammalian hair cell synapses have demonstrated a role of the AZ protein Bassoon, functionally related to Brp (Hallermann and Silver, 2013), in shaping Ca 2+ channel arrangement and establishing release sites (Frank et al., 2010). Despite the high spatial resolution provided by SRM, estimates of protein abundance are mainly obtained from fluorescence intensity measurements and therefore deliver only relative values. "
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    ABSTRACT: Brain function relies on accurate information transfer at chemical synapses. At the presynaptic active zone (AZ) a variety of specialized proteins are assembled to complex architectures, which set the basis for speed, precision and plasticity of synaptic transmission. Calcium channels are pivotal for the initiation of excitation-secretion coupling and, correspondingly, capture a central position at the AZ. Combining quantitative functional studies with modeling approaches has provided predictions of channel properties, numbers and even positions on the nanometer scale. However, elucidating the nanoscopic organization of the surrounding protein network requires direct ultrastructural access. Without this information, knowledge of molecular synaptic structure-function relationships remains incomplete. Recently, super-resolution microscopy (SRM) techniques have begun to enter the neurosciences. These approaches combine high spatial resolution with the molecular specificity of fluorescence microscopy. Here, we discuss how SRM can be used to obtain information on the organization of AZ proteins.
    Frontiers in Cellular Neuroscience 01/2015; 9:7. DOI:10.3389/fncel.2015.00007 · 4.29 Impact Factor
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