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","3980"],["dc.bibliographiccitation.issue","24"],["dc.bibliographiccitation.journal","Neuron"],["dc.bibliographiccitation.lastpage","4000.e7"],["dc.bibliographiccitation.volume","109"],["dc.contributor.author","Lipstein, Noa"],["dc.contributor.author","Chang, Shuwen"],["dc.contributor.author","Lin, Kun-Han"],["dc.contributor.author","López-Murcia, Francisco José"],["dc.contributor.author","Neher, Erwin"],["dc.contributor.author","Taschenberger, Holger"],["dc.contributor.author","Brose, Nils"],["dc.date.accessioned","2022-01-11T14:05:37Z"],["dc.date.available","2022-01-11T14:05:37Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1016/j.neuron.2021.09.054"],["dc.identifier.pii","S0896627321007273"],["dc.identifier.pmid","34706220"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97705"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/401"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/139"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-507"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation.issn","0896-6273"],["dc.relation.workinggroup","RG Brose"],["dc.relation.workinggroup","RG Neher (Membrane Biophysics)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.title","Munc13-1 is a Ca2+-phospholipid-dependent vesicle priming hub that shapes synaptic short-term plasticity and enables sustained neurotransmission"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","182"],["dc.bibliographiccitation.journal","Neuroscience"],["dc.bibliographiccitation.lastpage","202"],["dc.bibliographiccitation.volume","458"],["dc.contributor.author","Neher, Erwin"],["dc.contributor.author","Taschenberger, Holger"],["dc.date.accessioned","2021-04-14T08:28:52Z"],["dc.date.available","2021-04-14T08:28:52Z"],["dc.date.issued","2021"],["dc.description.abstract","Synaptic vesicles (SVs) undergo multiple steps of functional maturation (priming) before being fusion competent. We present an analysis technique, which decomposes the time course of quantal release during repetitive stimulation as a sum of contributions of SVs, which existed in distinct functional states prior to stimulation. Such states may represent different degrees of maturation in priming or relate to different molecular composition of the release apparatus. We apply the method to rat calyx of Held synapses. These synapses display a high degree of variability, both with respect to synaptic strength and short-term plasticity during high-frequency stimulus trains. The method successfully describes time courses of quantal release at individual synapses as linear combinations of three components, representing contributions from functionally distinct SV subpools, with variability among synapses largely covered by differences in subpool sizes. Assuming that SVs transit in sequence through at least two priming steps before being released by an action potential (AP) we interpret the components as representing SVs which had been ‘fully primed’, ‘incompletely primed’ or undocked prior to stimulation. Given these assumptions, the analysis reports an initial release probability of 0.43 for SVs that were fully primed prior to stimulation. Release probability of that component was found to increase during high-frequency stimulation, leading to rapid depletion of that subpool. SVs that were incompletely primed at rest rapidly obtain fusion-competence during repetitive stimulation and contribute the majority of release after 3–5 stimuli."],["dc.identifier.doi","10.1016/j.neuroscience.2020.10.012"],["dc.identifier.pmid","33454165"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82726"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/115"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/88"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation.issn","0306-4522"],["dc.relation.workinggroup","RG Neher (Membrane Biophysics)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.title","Non-negative Matrix Factorization as a Tool to Distinguish Between Synaptic Vesicles in Different Functional States"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","P219"],["dc.bibliographiccitation.journal","BMC Neuroscience"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Bibitchkov, Dmitry"],["dc.contributor.author","Taschenberger, Holger"],["dc.contributor.author","Neher, Erwin"],["dc.date.accessioned","2010-11-25T19:28:52Z"],["dc.date.accessioned","2011-06-29T15:42:22Z"],["dc.date.accessioned","2021-10-27T13:11:08Z"],["dc.date.available","2010-11-25T19:28:52Z"],["dc.date.available","2011-06-29T15:42:22Z"],["dc.date.available","2021-10-27T13:11:08Z"],["dc.date.issued","2009"],["dc.date.updated","2010-11-25T19:28:52Z"],["dc.description.abstract","The calyx of Held is a giant synaptic terminal in the MNTB of the auditory brainstem. Observations of postsynaptic responses to repeated stimulation reveal that this synapse exhibits complex behavior, which results from the interplay between processes such as vesicle pool depletion, activity-dependent recovery from depletion, synaptic facilitation and postsynaptic receptor desensitization. Intracellular calcium concentration ([Ca2+]) plays an important role in the neurotransmitter release and the regulation of short-term plasticity [1]. We build a detailed computational model of the synaptic transmission at the calyx, which captures all the above mentioned processes and includes the dynamics of calcium and its influence on the parameters of synaptic dynamics. The model is based on electrophysiological data obtained by patch clamp recordings from postsynaptic MNTB cells in rat brainstem slices. Calcium dynamics and the functional dependences of synaptic parameters on [Ca2+] are modeled based on previously published data [2]. Stimulating the synapse at different frequencies (from 0.2 to 200 Hz) and using pharmacological manipulations, we were able to separate contributions of different processes and determine the parameters of synaptic dynamics, which fit experimental data. We compare the fit with the previous phenomenological model [3], which does not include explicit dynamics of intracellular Ca2+."],["dc.identifier.doi","10.1186/1471-2202-10-S1-P219"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5753"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/91564"],["dc.language.iso","en"],["dc.language.rfc3066","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.orgunit","Fakultät für Biologie und Psychologie"],["dc.rights","CC BY 2.0"],["dc.rights.holder","et al.; licensee BioMed Central Ltd."],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.subject.ddc","570"],["dc.title","Model of synaptic transmission in the calyx of Held"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["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"]]