Neher, Erwin

[["dc.bibliographiccitation.firstpage","8272"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","The Journal of neuroscience"],["dc.bibliographiccitation.lastpage","8290"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Chang, Shuwen"],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Pedersen, Meike"],["dc.contributor.author","Neher, Erwin"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Taschenberger, Holger"],["dc.date.accessioned","2017-09-07T11:44:23Z"],["dc.date.available","2017-09-07T11:44:23Z"],["dc.date.issued","2015"],["dc.description.abstract","Complexins (Cplxs) are small synaptic proteins that cooperate with SNARE-complexes in the control of synaptic vesicle (SV) fusion. Studies involving genetic mutation, knock-down, or knock-out indicated two key functions of Cplx that are not mutually exclusive but cannot easily be reconciled, one in facilitating SV fusion, and one in \"clamping\" SVs to prevent premature fusion. Most studies on the role of Cplxs in mammalian synapse function have relied on cultured neurons, heterologous expression systems, or membrane fusion assays in vitro, whereas little is known about the function of Cplxs in native synapses. We therefore studied consequences of genetic ablation of Cplx1 in the mouse calyx of Held synapse, and discovered a developmentally exacerbating phenotype of reduced spontaneous and evoked transmission but excessive asynchronous release after stimulation, compatible with combined facilitating and clamping functions of Cplx1. Because action potential waveforms, Ca2+ influx, readily releasable SV pool size, and quantal size were unaltered, the reduced synaptic strength in the absence of Cplx1 is most likely a consequence of a decreased release probability, which is caused, in part, by less tight coupling between Ca2+ channels and docked SV. We found further that the excessive asynchronous release in Cplx1-deficient calyces triggered aberrant action potentials in their target neurons, and slowed-down the recovery of EPSCs after depleting stimuli. The augmented asynchronous release had a delayed onset and lasted hundreds of milliseconds, indicating that it predominantly represents fusion of newly recruited SVs, which remain unstable and prone to premature fusion in the absence of Cplx1."],["dc.identifier.doi","10.1523/JNEUROSCI.4841-14.2015"],["dc.identifier.gro","3141895"],["dc.identifier.isi","000356673100020"],["dc.identifier.pmid","26019341"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2267"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0270-6474"],["dc.title","Complexin Stabilizes Newly Primed Synaptic Vesicles and Prevents Their Premature Fusion at the Mouse Calyx of Held Synapse"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e2207987119"],["dc.bibliographiccitation.issue","34"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.volume","119"],["dc.contributor.author","Lin, Kun-Han"],["dc.contributor.author","Taschenberger, Holger"],["dc.contributor.author","Neher, Erwin"],["dc.date.accessioned","2022-09-01T09:50:23Z"],["dc.date.available","2022-09-01T09:50:23Z"],["dc.date.issued","2022"],["dc.description.abstract","Glutamatergic synapses display variable strength and diverse short-term plasticity (STP), even for a given type of connection. Using nonnegative tensor factorization and conventional state modeling, we demonstrate that a kinetic scheme consisting of two sequential and reversible steps of release–machinery assembly and a final step of synaptic vesicle (SV) fusion reproduces STP and its diversity among synapses. Analyzing transmission at the calyx of Held synapses reveals that differences in synaptic strength and STP are not primarily caused by variable fusion probability (\n \n p\n fusion\n \n ) but are determined by the fraction of docked synaptic vesicles equipped with a mature release machinery. Our simulations show that traditional quantal analysis methods do not necessarily report\n \n p\n fusion\n \n of SVs with a mature release machinery but reflect both\n \n p\n fusion\n \n and the distribution between mature and immature priming states at rest. Thus, the approach holds promise for a better mechanistic dissection of the roles of presynaptic proteins in the sequence of SV docking, two-step priming, and fusion. It suggests a mechanism for activity-induced redistribution of synaptic efficacy."],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft 501100001659"],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft 501100001659"],["dc.identifier.doi","10.1073/pnas.2207987119"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113696"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-597"],["dc.relation.eissn","1091-6490"],["dc.relation.issn","0027-8424"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0/"],["dc.title","A sequential two-step priming scheme reproduces diversity in synaptic strength and short-term plasticity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","82"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neuron"],["dc.bibliographiccitation.lastpage","96"],["dc.bibliographiccitation.volume","79"],["dc.contributor.author","Lipstein, Noa"],["dc.contributor.author","Sakaba, Takeshi"],["dc.contributor.author","Cooper, Benjamin H."],["dc.contributor.author","Lin, Kun-Han"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Ashery, Uri"],["dc.contributor.author","Rhee, Jeong-Seop"],["dc.contributor.author","Taschenberger, Holger"],["dc.contributor.author","Neher, Erwin"],["dc.contributor.author","Brose, Nils"],["dc.date.accessioned","2017-09-07T11:47:39Z"],["dc.date.available","2017-09-07T11:47:39Z"],["dc.date.issued","2013"],["dc.description.abstract","Short-term synaptic plasticity, the dynamic alteration of synaptic strength during high-frequency activity, is a fundamental characteristic of all synapses. At the calyx of Held, repetitive activity eventually results in short-term synaptic depression, which is in part due to the gradual exhaustion of releasable synaptic vesicles. This is counterbalanced by Ca²⁺-dependent vesicle replenishment, but the molecular mechanisms of this replenishment are largely unknown. We studied calyces of Held in knockin mice that express a Ca²⁺-Calmodulin insensitive Munc13-1(W464R) variant of the synaptic vesicle priming protein Munc13-1. Calyces of these mice exhibit a slower rate of synaptic vesicle replenishment, aberrant short-term depression and reduced recovery from synaptic depression after high-frequency stimulation. Our data establish Munc13-1 as a major presynaptic target of Ca²⁺-Calmodulin signaling and show that the Ca²⁺-Calmodulin-Munc13-1 complex is a pivotal component of the molecular machinery that determines short-term synaptic plasticity characteristics."],["dc.identifier.doi","10.1016/j.neuron.2013.05.011"],["dc.identifier.gro","3142326"],["dc.identifier.isi","000321802000011"],["dc.identifier.pmid","23770256"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7042"],["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","Dynamic Control of Synaptic Vesicle Replenishment and Short-Term Plasticity by Ca²⁺-Calmodulin-Munc13-1 Signaling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","513"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","The Journal of Physiology"],["dc.bibliographiccitation.lastpage","537"],["dc.bibliographiccitation.volume","568"],["dc.contributor.author","Taschenberger, Holger"],["dc.contributor.author","Scheuss, Volker"],["dc.contributor.author","Neher, Erwin"],["dc.date.accessioned","2022-03-01T11:47:15Z"],["dc.date.available","2022-03-01T11:47:15Z"],["dc.date.issued","2005"],["dc.identifier.doi","10.1113/jphysiol.2005.093468"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103967"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0022-3751"],["dc.title","Release kinetics, quantal parameters and their modulation during short-term depression at a developing synapse in the rat CNS"],["dc.title.alternative","Fluctuation analysis at the developing calyx of Held"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]