Brose, Nils

[["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.firstpage","473"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Neuron"],["dc.bibliographiccitation.lastpage","487"],["dc.bibliographiccitation.volume","68"],["dc.contributor.author","Burgalossi, Andrea"],["dc.contributor.author","Jung, Sangyong"],["dc.contributor.author","Meyer, Guido"],["dc.contributor.author","Jockusch, Wolf J."],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Taschenberger, Holger"],["dc.contributor.author","O'Connor, V. M."],["dc.contributor.author","Nishiki, Tei-ichi"],["dc.contributor.author","Takahashi, Masami"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Rhee, Jeong-Seop"],["dc.date.accessioned","2017-09-07T11:45:13Z"],["dc.date.available","2017-09-07T11:45:13Z"],["dc.date.issued","2010"],["dc.description.abstract","Neurotransmitter release proceeds by Ca(2+)-triggered, SNARE-complex-dependent synaptic vesicle fusion. After fusion, the ATPase NSF and its cofactors alpha- and beta SNAP disassemble SNARE complexes, thereby recycling individual SNAREs for subsequent fusion reactions. We examined the effects of genetic perturbation of alpha- and beta SNAP expression on synaptic vesicle exocytosis, employing a new Ca(2+) uncaging protocol to study synaptic vesicle trafficking, priming, and fusion in small glutamatergic synapses of hippocampal neurons. By characterizing this protocol, we show that synchronous and asynchronous transmitter release involve different Ca(2+) sensors and are not caused by distinct releasable vesicle pools, and that tonic transmitter release is due to ongoing priming and fusion of new synaptic vesicles during high synaptic activity. Our analysis of alpha- and beta SNAP deletion mutant neurons shows that the two NSF cofactors support synaptic vesicle priming by determining the availability of free SNARE components, particularly during phases of high synaptic activity."],["dc.identifier.doi","10.1016/j.neuron.2010.09.019"],["dc.identifier.gro","3142831"],["dc.identifier.isi","000284255800015"],["dc.identifier.pmid","21040848"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/278"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Max Planck Society; European Community [MEST-CT-2004-504193]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0896-6273"],["dc.title","SNARE Protein Recycling by alpha SNAP and beta SNAP Supports Synaptic Vesicle Priming"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1005"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","The Journal of Clinical Investigation"],["dc.bibliographiccitation.lastpage","1018"],["dc.bibliographiccitation.volume","127"],["dc.contributor.author","Lipstein, Noa"],["dc.contributor.author","Verhoeven-Duif, Nanda M."],["dc.contributor.author","Michelassi, Francesco E."],["dc.contributor.author","Calloway, Nathaniel"],["dc.contributor.author","van Hasselt, Peter M."],["dc.contributor.author","Pienkowska, Katarzyna"],["dc.contributor.author","van Haaften, Gijs"],["dc.contributor.author","van Haelst, Mieke M."],["dc.contributor.author","van Empelen, Ron"],["dc.contributor.author","Cuppen, Inge"],["dc.contributor.author","van Teeseling, Heleen C."],["dc.contributor.author","Evelein, Annemieke M.V."],["dc.contributor.author","Vorstman, Jacob A."],["dc.contributor.author","Thoms, Sven"],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Duran, Karen J."],["dc.contributor.author","Monroe, Glen R."],["dc.contributor.author","Ryan, Timothy A."],["dc.contributor.author","Taschenberger, Holger"],["dc.contributor.author","Dittman, Jeremy S."],["dc.contributor.author","Rhee, Jeong-Seop"],["dc.contributor.author","Visser, Gepke"],["dc.contributor.author","Jans, Judith J."],["dc.contributor.author","Brose, Nils"],["dc.date.accessioned","2020-12-10T18:38:19Z"],["dc.date.available","2020-12-10T18:38:19Z"],["dc.date.issued","2017"],["dc.description.abstract","Munc13 proteins are essential regulators of neurotransmitter release at nerve cell synapses. They mediate the priming step that renders synaptic vesicles fusion-competent, and their genetic elimination causes a complete block of synaptic transmission. Here we have described a patient displaying a disorder characterized by a dyskinetic movement disorder, developmental delay, and autism. Using whole-exome sequencing, we have shown that this condition is associated with a rare, de novo Pro814Leu variant in the major human Munc13 paralog UNC13A (also known as Munc13-1). Electrophysiological studies in murine neuronal cultures and functional analyses in Caenorhabditis elegans revealed that the UNC13A variant causes a distinct dominant gain of function that is characterized by increased fusion propensity of synaptic vesicles, which leads to increased initial synaptic vesicle release probability and abnormal short-term synaptic plasticity. Our study underscores the critical importance of fine-tuned presynaptic control in normal brain function. Further, it adds the neuronal Munc13 proteins and the synaptic vesicle priming process that they control to the known etiological mechanisms of psychiatric and neurological synaptopathies."],["dc.identifier.doi","10.1172/JCI90259"],["dc.identifier.eissn","1558-8238"],["dc.identifier.issn","0021-9738"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77270"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.status","final"],["dc.relation.doi","10.1172/JCI90259"],["dc.relation.eissn","1558-8238"],["dc.relation.issn","0021-9738"],["dc.title","Synaptic UNC13A protein variant causes increased neurotransmission and dyskinetic movement disorder"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"],["local.message.claim","2020-08-07T08:23:16.626+0000|||rp114519|||submit_approve|||dc_contributor_author|||None"]]

[["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","3053"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","3058"],["dc.bibliographiccitation.volume","108"],["dc.contributor.author","Hoon, Mrinalini"],["dc.contributor.author","Soykan, Tolga"],["dc.contributor.author","Falkenburger, Björn"],["dc.contributor.author","Hammer, Matthieu"],["dc.contributor.author","Patrizi, Annarita"],["dc.contributor.author","Schmidt, Karl-Friedrich"],["dc.contributor.author","Sassoè-Pognetto, Marco"],["dc.contributor.author","Löwel, Siegrid"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Taschenberger, Holger"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Varoqueaux, Frédérique"],["dc.date.accessioned","2017-09-07T11:44:21Z"],["dc.date.available","2017-09-07T11:44:21Z"],["dc.date.issued","2011"],["dc.description.abstract","Neuroligins (NL1-NL4) are postsynaptic adhesion proteins that control the maturation and function of synapses in the central nervous system (CNS). Loss-of-function mutations in NL4 are linked to rare forms of monogenic heritable autism, but its localization and function are unknown. Using the retina as a model system, we show that NL4 is preferentially localized to glycinergic postsynapses and that the loss of NL4 is accompanied by a reduced number of glycine receptors mediating fast glycinergic transmission. Accordingly, NL4-deficient ganglion cells exhibit slower glycinergic miniature postsynaptic currents and subtle alterations in their stimuluscoding efficacy, and inhibition within the NL4-deficient retinal network is altered as assessed by electroretinogram recordings. These data indicate that NL4 shapes network activity and information processing in the retina by modulating glycinergic inhibition. Importantly, NL4 is also targeted to inhibitory synapses in other areas of the CNS, such as the thalamus, colliculi, brainstem, and spinal cord, and forms complexes with the inhibitory postsynapse proteins gephyrin and collybistin in vivo, indicating that NL4 is an important component of glycinergic postsynapses."],["dc.identifier.doi","10.1073/pnas.1006946108"],["dc.identifier.gro","3142775"],["dc.identifier.isi","000287377000078"],["dc.identifier.pmid","21282647"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/216"],["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","0027-8424"],["dc.title","Neuroligin-4 is localized to glycinergic postsynapses and regulates inhibition in the retina"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","516"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.lastpage","523"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Hammer, Matthieu"],["dc.contributor.author","Krueger-Burg, Dilja"],["dc.contributor.author","Tuffy, Liam Patrick"],["dc.contributor.author","Cooper, Benjamin Hillman"],["dc.contributor.author","Taschenberger, Holger"],["dc.contributor.author","Goswami, Sarit Pati"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Jonas, Peter"],["dc.contributor.author","Varoqueaux, Frederique"],["dc.contributor.author","Rhee, Jeong-Seop"],["dc.contributor.author","Brose, Nils"],["dc.date.accessioned","2017-09-07T11:46:34Z"],["dc.date.available","2017-09-07T11:46:34Z"],["dc.date.issued","2015"],["dc.description.abstract","Loss-of-function mutations in the synaptic adhesion protein Neuroligin-4 are among the most common genetic abnormalities associated with autism spectrum disorders, but little is known about the function of Neuroligin-4 and the consequences of its loss. We assessed synaptic and network characteristics in Neuroligin-4 knockout mice, focusing on the hippocampus as a model brain region with a critical role in cognition and memory, and found that Neuroligin-4 deletion causes subtle defects of the protein composition and function of GABAergic synapses in the hippocampal CA3 region. Interestingly, these subtle synaptic changes are accompanied by pronounced perturbations of γ-oscillatory network activity, which has been implicated in cognitive function and is altered in multiple psychiatric and neurodevelopmental disorders. Our data provide important insights into the mechanisms by which Neuroligin-4-dependent GABAergic synapses may contribute to autism phenotypes and indicate new strategies for therapeutic approaches."],["dc.identifier.doi","10.1016/j.celrep.2015.09.011"],["dc.identifier.gro","3150543"],["dc.identifier.pmid","26456829"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7316"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Perturbed Hippocampal Synaptic Inhibition and γ-Oscillations in a Neuroligin-4 Knockout Mouse Model of Autism"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","620"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Neuron"],["dc.bibliographiccitation.volume","73"],["dc.contributor.author","Burgalossi, Andrea"],["dc.contributor.author","Jung, Sangyong"],["dc.contributor.author","Meyer, Guido"],["dc.contributor.author","Jockusch, Wolf J."],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Taschenberger, Holger"],["dc.contributor.author","O'Connor, Vincent M."],["dc.contributor.author","Nishiki, Tei-ichi"],["dc.contributor.author","Takahashi, Masami"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Rhee, Jeong-Seop"],["dc.date.accessioned","2022-03-01T11:45:20Z"],["dc.date.available","2022-03-01T11:45:20Z"],["dc.date.issued","2012"],["dc.identifier.doi","10.1016/j.neuron.2012.01.015"],["dc.identifier.pii","S0896627312000979"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103295"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0896-6273"],["dc.title","SNARE Protein Recycling by αSNAP and βSNAP Supports Synaptic Vesicle Priming"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]