Neef, Andreas

[["dc.bibliographiccitation.firstpage","12933"],["dc.bibliographiccitation.issue","47"],["dc.bibliographiccitation.journal","The Journal of neuroscience"],["dc.bibliographiccitation.lastpage","12944"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Pirih, Primoz"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Wolf, Fred"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:49:23Z"],["dc.date.available","2017-09-07T11:49:23Z"],["dc.date.issued","2007"],["dc.description.abstract","Hearing relies on faithful synaptic transmission at the ribbon synapse of cochlear inner hair cells (IHCs). Postsynaptic recordings from this synapse in prehearing animals had delivered strong indications for synchronized release of several vesicles. The underlying mechanism, however, remains unclear. Here, we used presynaptic membrane capacitance measurements to test whether IHCs release vesicles in a statistically independent or dependent ( coordinated) manner. Exocytic changes of membrane capacitance (Delta C-m) were repeatedly stimulated in IHCs of prehearing and hearing mice by short depolarizations to preferentially recruit the readily releasable pool of synaptic vesicles. A compound Poisson model was devised to describe hair cell exocytosis and to test the analysis. From the trial-to-trial fluctuations of the Delta C-m we were able to estimate the apparent size of the elementary fusion event (C-app) at the hair cell synapse to be 96-223 aF in immature and 55-149 aF in mature IHCs. We also approximated the single vesicle capacitance in IHCs by measurements of synaptic vesicle diameters in electron micrographs. The results (immature, 48 aF; mature, 45 aF) were lower than the respective Capp estimates. This indicates that coordinated exocytosis of synaptic vesicles occurs at both immature and mature hair cell synapses. Approximately 35% of the release events in mature IHCs and similar to 50% in immature IHCs were predicted to involve coordinated fusion, when assuming a geometric distribution of elementary sizes. In summary, our presynaptic measurements indicate coordinated exocytosis but argue for a lesser degree of coordination than suggested by postsynaptic recordings."],["dc.identifier.doi","10.1523/JNEUROSCI.1996-07.2007"],["dc.identifier.gro","3143408"],["dc.identifier.isi","000251157200022"],["dc.identifier.pmid","18032667"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/919"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Soc Neuroscience"],["dc.relation.issn","0270-6474"],["dc.title","Probing the mechanism of exocytosis at the hair cell ribbon synapse"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4483"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","4488"],["dc.bibliographiccitation.volume","106"],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:47:32Z"],["dc.date.available","2017-09-07T11:47:32Z"],["dc.date.issued","2009"],["dc.description.abstract","Sound coding at hair cell ribbon synapses is tightly regulated by Ca2+. Here, we used patch-clamp, fast confocal Ca2+ imaging and modeling to characterize synaptic Ca2+ signaling in cochlear inner hair cells (IHCs) of hearing mice. Submicrometer fluorescence hotspots built up and collapsed at the base of IHCs within a few milliseconds of stimulus onset and cessation. They most likely represented Ca2+ microdomains arising from synaptic Ca2+ influx through Ca(V)1.3 channels. Synaptic Ca2+ microdomains varied substantially in amplitude and voltage dependence even within single IHCs. Testing putative mechanisms for the heterogeneity of Ca2+ signaling, we found the amplitude variability unchanged when blocking mitochondrial Ca2+ uptake or Ca2+-induced Ca2+ release, buffering cytosolic Ca2+ by millimolar concentrations of EGTA, or elevating the Ca2+ channel open probability by the dihydropyridine agonist BayK8644. However, we observed substantial variability also for the fluorescence of immunolabeled Ca(V)1.3 Ca2+ channel clusters. Moreover, the Ca2+ microdomain amplitude correlated positively with the size of the corresponding synaptic ribbon. Ribbon size, previously suggested to scale with the number of synaptic Ca2+ channels, was approximated by using fluorescent peptide labeling. We propose that IHCs adjust the number and the gating of Ca(V)1.3 channels at their active zones to diversify their transmitter release rates."],["dc.identifier.doi","10.1073/pnas.0813213106"],["dc.identifier.gro","3143138"],["dc.identifier.isi","000264278800077"],["dc.identifier.pmid","19246382"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/619"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","Mechanisms contributing to synaptic Ca2+ signals and their heterogeneity in hair cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","724"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Neuron"],["dc.bibliographiccitation.lastpage","738"],["dc.bibliographiccitation.volume","68"],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Rutherford, Mark A."],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Pangrsic, Tina"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Fetjova, Anna"],["dc.contributor.author","Gundelfinger, Eckart D."],["dc.contributor.author","Liberman, M. Charles"],["dc.contributor.author","Harke, Benjamin"],["dc.contributor.author","Bryan, Keith E."],["dc.contributor.author","Lee, Amy"],["dc.contributor.author","Egner, Alexander"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:45:13Z"],["dc.date.available","2017-09-07T11:45:13Z"],["dc.date.issued","2010"],["dc.description.abstract","At the presynaptic active zone, Ca2+ influx triggers fusion of synaptic vesicles. It is not well understood how Ca2+ channel clustering and synaptic vesicle docking are organized. Here, we studied structure and function of hair cell ribbon synapses following genetic disruption of the presynaptic scaffold protein Bassoon. Mutant synapses-mostly lacking the ribbon-showed a reduction in membrane-proximal vesicles, with ribbonless synapses affected more than ribbon-occupied synapses. Ca2+ channels were also fewer at mutant synapses and appeared in abnormally shaped clusters. Ribbon absence reduced Ca2+ channel numbers at mutant and wildtype synapses. Fast and sustained exocytosis was reduced, notwithstanding normal coupling of the remaining Ca2+ channels to exocytosis. In vitro recordings revealed a slight impairment of vesicle replenishment. Mechanistic modeling of the in vivo data independently supported morphological and functional in vitro findings. We conclude that Bassoon and the ribbon (1) create a large number of release sites by organizing Ca2+ channels and vesicles, and (2) promote vesicle replenishment."],["dc.identifier.doi","10.1016/j.neuron.2010.10.027"],["dc.identifier.gro","3142827"],["dc.identifier.isi","000285079500011"],["dc.identifier.pmid","21092861"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/274"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Cell Press"],["dc.relation.issn","0896-6273"],["dc.title","Bassoon and the Synaptic Ribbon Organize Ca2+ Channels and Vesicles to Add Release Sites and Promote Refilling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","7991"],["dc.bibliographiccitation.issue","25"],["dc.bibliographiccitation.journal","The Journal of neuroscience"],["dc.bibliographiccitation.lastpage","8004"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Chanda, Soham"],["dc.contributor.author","Kopp-Scheinpflug, Cornelia"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Bulankina, Anna V."],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Wolf, Fred"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Xu-Friedman, Matthew A."],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:47:26Z"],["dc.date.available","2017-09-07T11:47:26Z"],["dc.date.issued","2009"],["dc.description.abstract","Complexins (CPXs I-IV) presumably act as regulators of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex, but their function in the intact mammalian nervous system is not well established. Here, we explored the role of CPXs in the mouse auditory system. Hearing was impaired in CPXI knock-out mice but normal in knock-out mice for CPXs II, III, IV, and III/IV as measured by auditory brainstem responses. Complexins were not detectable in cochlear hair cells but CPX I was expressed in spiral ganglion neurons (SGNs) that give rise to the auditory nerve. Ca(2+)-dependent exocytosis of inner hair cells and sound encoding by SGNs were unaffected in CPX I knock-out mice. In the absence of CPX I, the resting release probability in the endbulb of Held synapses of the auditory nerve fibers with bushy cells in the cochlear nucleus was reduced. As predicted by computational modeling, bushy cells had decreased spike rates at sound onset as well as longer and more variable first spike latencies explaining the abnormal auditory brainstem responses. In addition, we found synaptic transmission to outlast the stimulus at many endbulb of Held synapses in vitro and in vivo, suggesting impaired synchronization of release to stimulus offset. Although sound encoding in the cochlea proceeds in the absence of complexins, CPX I is required for faithful processing of sound onset and offset in the cochlear nucleus."],["dc.identifier.doi","10.1523/JNEUROSCI.0632-09.2009"],["dc.identifier.gro","3143100"],["dc.identifier.isi","000267339000006"],["dc.identifier.pmid","19553439"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/577"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Soc Neuroscience"],["dc.relation.issn","0270-6474"],["dc.title","Complexin-I Is Required for High-Fidelity Transmission at the Endbulb of Held Auditory Synapse"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","55"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of Physiology"],["dc.bibliographiccitation.lastpage","62"],["dc.bibliographiccitation.volume","576"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Khimich, Darina"],["dc.date.accessioned","2017-09-07T11:52:33Z"],["dc.date.available","2017-09-07T11:52:33Z"],["dc.date.issued","2006"],["dc.description.abstract","Our auditory system is capable of perceiving the azimuthal location of a low frequency sound source with a precision of a few degrees. This requires the auditory system to detect time differences in sound arrival between the two ears down to tens of microseconds. The detection of these interaural time differences relies on network computation by auditory brainstem neurons sharpening the temporal precision of the afferent signals. Nevertheless, the system requires the hair cell synapse to encode sound with the highest possible temporal acuity. In mammals, each auditory nerve fibre receives input from only one inner hair cell (IHC) synapse. Hence, this single synapse determines the temporal precision of the fibre. As if this was not enough of a challenge, the auditory system is also capable of maintaining such high temporal fidelity with acoustic signals that vary greatly in their intensity. Recent research has started to uncover the cellular basis of sound coding. Functional and structural descriptions of synaptic vesicle pools and estimates for the number of Ca2+ channels at the ribbon synapse have been obtained, as have insights into how the receptor potential couples to the release of synaptic vesicles. Here, we review current concepts about the mechanisms that control the timing of transmitter release in inner hair cells of the cochlea."],["dc.identifier.doi","10.1113/jphysiol.2006.114835"],["dc.identifier.gro","3143618"],["dc.identifier.isi","000241162800010"],["dc.identifier.pmid","16901948"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1152"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","0022-3751"],["dc.title","Mechanisms underlying the temporal precision of sound coding at the inner hair cell ribbon synapse"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1202"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Neuron"],["dc.bibliographiccitation.volume","68"],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Rutherford, Mark A."],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Pangrsic, Tina"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Fejtova, Anna"],["dc.contributor.author","Gundelfinger, Eckart D."],["dc.contributor.author","Liberman, M. Charles"],["dc.contributor.author","Harke, Benjamin"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2022-03-01T11:45:20Z"],["dc.date.available","2022-03-01T11:45:20Z"],["dc.date.issued","2010"],["dc.identifier.doi","10.1016/j.neuron.2010.12.020"],["dc.identifier.pii","S0896627310010433"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103294"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0896-6273"],["dc.title","Bassoon and the Synaptic Ribbon Organize Ca2+ Channels and Vesicles to Add Release Sites and Promote Refilling"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","BMC Neuroscience"],["dc.bibliographiccitation.lastpage","1"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Chapochnikov, Nikolai M."],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Egner, Alexander"],["dc.contributor.author","Wolf, Fred"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2011-04-12T13:30:30Z"],["dc.date.accessioned","2021-10-11T11:34:47Z"],["dc.date.available","2011-04-12T13:30:30Z"],["dc.date.available","2021-10-11T11:34:47Z"],["dc.date.issued","2009"],["dc.identifier.citation","Chapochnikov, Nikolai M; Frank, Thomas; Strenzke, Nicola; Neef, Andreas; Khimich, Darina; Egner, Alexander; Wolf, Fred; Moser, Tobias (2009): Modeling the origin of functional heterogeneity among auditory nerve fibers - BMC Neuroscience, Vol. 10, Nr. Suppl 1, p. P220-"],["dc.identifier.doi","10.1186/1471-2202-10-S1-P220"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6101"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/90701"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.orgunit","Fakultät für Physik"],["dc.rights","Goescholar"],["dc.rights.access","openAccess"],["dc.rights.uri","http://goedoc.uni-goettingen.de/licenses"],["dc.subject","heterogeneity; auditory nerve fibers"],["dc.subject.ddc","530"],["dc.subject.ddc","573"],["dc.subject.ddc","573.8"],["dc.subject.ddc","612"],["dc.subject.ddc","612.8"],["dc.title","Modeling the origin of functional heterogeneity among auditory nerve fibers"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]