Wichmann, Carolin

[["dc.bibliographiccitation.firstpage","95"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cell and Tissue Research"],["dc.bibliographiccitation.lastpage","114"],["dc.bibliographiccitation.volume","361"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:43:44Z"],["dc.date.available","2017-09-07T11:43:44Z"],["dc.date.issued","2015"],["dc.description.abstract","In the mammalian cochlea, sound is encoded at synapses between inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs). Each SGN receives input from a single IHC ribbon-type active zone (AZ) and yet SGNs indefatigably spike up to hundreds of Hz to encode acoustic stimuli with submillisecond precision. Accumulating evidence indicates a highly specialized molecular composition and structure of the presynapse, adapted to suit these high functional demands. However, we are only beginning to understand key features such as stimulus-secretion coupling, exocytosis mechanisms, exo-endocytosis coupling, modes of endocytosis and vesicle reformation, as well as replenishment of the readily releasable pool. Relating structure and function has become an important avenue in addressing these points and has been applied to normal and genetically manipulated hair cell synapses. Here, we review some of the exciting new insights gained from recent studies of the molecular anatomy and physiology of IHC ribbon synapses."],["dc.identifier.doi","10.1007/s00441-014-2102-7"],["dc.identifier.gro","3141877"],["dc.identifier.isi","000357115200009"],["dc.identifier.pmid","25874597"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11594"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2067"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Springer"],["dc.relation.eissn","1432-0878"],["dc.relation.issn","0302-766X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Relating structure and function of inner hair cell ribbon synapses"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","102282"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","iScience"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Hintze, Anika"],["dc.contributor.author","Gültas, Mehmet"],["dc.contributor.author","Semmelhack, Esther A."],["dc.contributor.author","Wichmann, Carolin"],["dc.date.accessioned","2021-06-01T09:41:21Z"],["dc.date.available","2021-06-01T09:41:21Z"],["dc.date.issued","2021"],["dc.description.abstract","Endbulbs of Held are located in the anteroventral cochlear nucleus and present the first central synapses of the auditory pathway. During development, endbulbs mature functionally to enable rapid and powerful synaptic transmission with high temporal precision. This process is accompanied by morphological changes of endbulb terminals. Loss of the hair cell-specific protein otoferlin (Otof) abolishes neurotransmission in the cochlea and results in the smaller endbulb of Held terminals. Thus, peripheral hearing impairment likely also leads to alterations in the morphological synaptic vesicle (SV) pool size at individual endbulb of Held active zones (AZs). Here, we investigated endbulb AZs in pre-hearing, young, and adult wild-type and Otof−/− mice. During maturation, SV numbers at endbulb AZs increased in wild-type mice but were found to be reduced in Otof−/− mice. The SV population at a distance of 0–15 nm was most strongly affected. Finally, overall SV diameters decreased in Otof−/− animals during maturation."],["dc.identifier.doi","10.1016/j.isci.2021.102282"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84891"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/112"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | A04: Aktivitätsabhängige morphologische Veränderungen am Endkolben von Held-Synapsen"],["dc.relation.issn","2589-0042"],["dc.relation.workinggroup","RG Wichmann (Molecular Architecture of Synapses)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.title","Ultrastructural maturation of the endbulb of Held active zones comparing wild-type and otoferlin-deficient mice"],["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","2147"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","20"],["dc.contributor.affiliation","Chakrabarti, Rituparna; \t\t \r\n\t\t Molecular Architecture of Synapses Group, Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, 37075 Göttingen, Germany, rituparna.chakrabarti@med.uni-goettingen.de\t\t \r\n\t\t Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, 37075 Göttingen, Germany, rituparna.chakrabarti@med.uni-goettingen.de\t\t \r\n\t\t Collaborative Research Center 889 “Cellular Mechanisms of Sensory Processing”, 37099 Göttingen, Germany, rituparna.chakrabarti@med.uni-goettingen.de"],["dc.contributor.affiliation","Wichmann, Carolin; \t\t \r\n\t\t Molecular Architecture of Synapses Group, Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, 37075 Göttingen, Germany, carolin.wichmann@med.uni-goettingen.de\t\t \r\n\t\t Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, 37075 Göttingen, Germany, carolin.wichmann@med.uni-goettingen.de\t\t \r\n\t\t Collaborative Research Center 889 “Cellular Mechanisms of Sensory Processing”, 37099 Göttingen, Germany, carolin.wichmann@med.uni-goettingen.de\t\t \r\n\t\t Collaborative Research Center 1286 “Quantitative Synaptology”, 37099 Göttingen, Germany, carolin.wichmann@med.uni-goettingen.de\t\t \r\n\t\t Auditory Neuroscience Group, Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany, carolin.wichmann@med.uni-goettingen.de"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Chakrabarti, Rituparna"],["dc.date.accessioned","2019-07-09T11:51:18Z"],["dc.date.available","2019-07-09T11:51:18Z"],["dc.date.issued","2019"],["dc.date.updated","2022-09-06T05:26:16Z"],["dc.description.abstract","A critical aim in neuroscience is to obtain a comprehensive view of how regulated neurotransmission is achieved. Our current understanding of synapses relies mainly on data from electrophysiological recordings, imaging, and molecular biology. Based on these methodologies, proteins involved in a synaptic vesicle (SV) formation, mobility, and fusion at the active zone (AZ) membrane have been identified. In the last decade, electron tomography (ET) combined with a rapid freezing immobilization of neuronal samples opened a window for understanding the structural machinery with the highest spatial resolution in situ. ET provides significant insights into the molecular architecture of the AZ and the organelles within the presynaptic nerve terminal. The specialized sensory ribbon synapses exhibit a distinct architecture from neuronal synapses due to the presence of the electron-dense synaptic ribbon. However, both synapse types share the filamentous structures, also commonly termed as tethers that are proposed to contribute to different steps of SV recruitment and exocytosis. In this review, we discuss the emerging views on the role of filamentous structures in SV exocytosis gained from ultrastructural studies of excitatory, mainly central neuronal compared to ribbon-type synapses with a focus on inner hair cell (IHC) ribbon synapses. Moreover, we will speculate on the molecular entities that may be involved in filament formation and hence play a crucial role in the SV cycle."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.3390/ijms20092147"],["dc.identifier.pmid","31052288"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16099"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59921"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/29"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | A04: Aktivitätsabhängige morphologische Veränderungen am Endkolben von Held-Synapsen"],["dc.relation.eissn","1422-0067"],["dc.relation.workinggroup","RG Wichmann (Molecular Architecture of Synapses)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Nanomachinery Organizing Release at Neuronal and Ribbon Synapses"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Jean, Philippe"],["dc.contributor.author","Anttonen, Tommi"],["dc.contributor.author","Michanski, Susann"],["dc.contributor.author","de Diego, Antonio M. G."],["dc.contributor.author","Steyer, Anna M."],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Oestreicher, David"],["dc.contributor.author","Kroll, Jana"],["dc.contributor.author","Nardis, Christos"],["dc.contributor.author","Pangršič, Tina"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Ashmore, Jonathan"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2021-04-14T08:25:48Z"],["dc.date.available","2021-04-14T08:25:48Z"],["dc.date.issued","2020"],["dc.description.abstract","Inner hair cells (IHCs) are the primary receptors for hearing. They are housed in the cochlea and convey sound information to the brain via synapses with the auditory nerve. IHCs have been thought to be electrically and metabolically independent from each other. We report that, upon developmental maturation, in mice 30% of the IHCs are electrochemically coupled in ‘mini-syncytia’. This coupling permits transfer of fluorescently-labeled metabolites and macromolecular tracers. The membrane capacitance, Ca2+-current, and resting current increase with the number of dye-coupled IHCs. Dual voltage-clamp experiments substantiate low resistance electrical coupling. Pharmacology and tracer permeability rule out coupling by gap junctions and purinoceptors. 3D electron microscopy indicates instead that IHCs are coupled by membrane fusion sites. Consequently, depolarization of one IHC triggers presynaptic Ca2+-influx at active zones in the entire mini-syncytium. Based on our findings and modeling, we propose that IHC-mini-syncytia enhance sensitivity and reliability of cochlear sound encoding."],["dc.identifier.doi","10.1038/s41467-020-17003-z"],["dc.identifier.pmid","32587250"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81736"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/383"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","2041-1723"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.relation.workinggroup","RG Möbius"],["dc.relation.workinggroup","RG Pangršič Vilfan (Experimental Otology)"],["dc.relation.workinggroup","RG Wichmann (Molecular Architecture of Synapses)"],["dc.rights","CC BY 4.0"],["dc.title","Macromolecular and electrical coupling between inner hair cells in the rodent cochlea"],["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","14"],["dc.bibliographiccitation.journal","Frontiers in synaptic neuroscience"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Butola, Tanvi"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2018-01-17T11:39:58Z"],["dc.date.available","2018-01-17T11:39:58Z"],["dc.date.issued","2017"],["dc.description.abstract","Piccolo and Bassoon are the two largest cytomatrix of the active zone (CAZ) proteins involved in scaffolding and regulating neurotransmitter release at presynaptic active zones (AZs), but have long been discussed as being functionally redundant. We employed genetic manipulation to bring forth and segregate the role of Piccolo from that of Bassoon at central auditory synapses of the cochlear nucleus-the endbulbs of Held. These synapses specialize in high frequency synaptic transmission, ideally poised to reveal even subtle deficits in the regulation of neurotransmitter release upon molecular perturbation. Combining semi-quantitative immunohistochemistry, electron microscopy, and in vitro and in vivo electrophysiology we first studied signal transmission in Piccolo-deficient mice. Our analysis was not confounded by a cochlear deficit, as a short isoform of Piccolo (\"Piccolino\") present at the upstream ribbon synapses of cochlear inner hair cells (IHC), is unaffected by the mutation. Disruption of Piccolo increased the abundance of Bassoon at the AZs of endbulbs, while that of RIM1 was reduced and other CAZ proteins remained unaltered. Presynaptic fiber stimulation revealed smaller amplitude of the evoked excitatory postsynaptic currents (eEPSC), while eEPSC kinetics as well as miniature EPSCs (mEPSCs) remained unchanged. Cumulative analysis of eEPSC trains indicated that the reduced eEPSC amplitude of Piccolo-deficient endbulb synapses is primarily due to a reduced readily releasable pool (RRP) of synaptic vesicles (SV), as was corroborated by a reduction of vesicles at the AZ found on an ultrastructural level. Release probability seemed largely unaltered. Recovery from short-term depression was slowed. We then performed a physiological analysis of endbulb synapses from mice which, in addition to Piccolo deficiency, lacked one functional allele of the Bassoon gene. Analysis of the double-mutant endbulbs revealed an increase in release probability, while the synapses still exhibited the reduced RRP, and the impairment in SV replenishment was exacerbated. We propose additive roles of Piccolo and Bassoon in SV replenishment which in turn influences the organization and size of the RRP, and an additional role of Bassoon in regulation of release probability."],["dc.format.extent","1"],["dc.identifier.doi","10.3389/fnsyn.2017.00014"],["dc.identifier.pmid","29118709"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11685"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/33"],["dc.language.iso","en"],["dc.notes.intern","DeepGreen Import"],["dc.notes.status","final"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | A04: Aktivitätsabhängige morphologische Veränderungen am Endkolben von Held-Synapsen"],["dc.relation","SFB 1286 | B05: Quantitative molekulare Physiologie aktiver Zonen in Calyx-Synapsen"],["dc.relation.eissn","1663-3563"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.relation.workinggroup","RG Wichmann (Molecular Architecture of Synapses)"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Piccolo Promotes Vesicle Replenishment at a Fast Central Auditory Synapse"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","334"],["dc.bibliographiccitation.journal","Frontiers in Cellular Neuroscience"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Krinner, Stefanie"],["dc.contributor.author","Butola, Tanvi"],["dc.contributor.author","Jung, SangYong"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2018-01-17T11:39:13Z"],["dc.date.available","2018-01-17T11:39:13Z"],["dc.date.issued","2017"],["dc.description.abstract","Ribbon synapses of inner hair cells (IHCs) mediate high rates of synchronous exocytosis to indefatigably track the stimulating sound with sub-millisecond precision. The sophisticated molecular machinery of the inner hair cell active zone realizes this impressive performance by enabling a large number of synaptic voltage-gated CaV1.3 Ca2+-channels, their tight coupling to synaptic vesicles (SVs) and fast replenishment of fusion competent SVs. Here we studied the role of RIM-binding protein 2 (RIM-BP2)-a multidomain cytomatrix protein known to directly interact with Rab3 interacting molecules (RIMs), bassoon and CaV1.3-that is present at the inner hair cell active zones. We combined confocal and stimulated emission depletion (STED) immunofluorescence microscopy, electron tomography, patch-clamp and confocal Ca2+-imaging, as well as auditory systems physiology to explore the morphological and functional effects of genetic RIM-BP2 disruption in constitutive RIM-BP2 knockout mice. We found that RIM-BP2 (1) positively regulates the number of synaptic CaV1.3 channels and thereby facilitates synaptic vesicle release and (2) supports fast synaptic vesicle recruitment after readily releasable pool (RRP) depletion. However, Ca2+-influx-exocytosis coupling seemed unaltered for readily releasable SVs. Recordings of auditory brainstem responses (ABR) and of single auditory nerve fiber firing showed that RIM-BP2 disruption results in a mild deficit of synaptic sound encoding."],["dc.format.extent","1"],["dc.identifier.doi","10.3389/fncel.2017.00334"],["dc.identifier.pmid","29163046"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14890"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11684"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/30"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | A04: Aktivitätsabhängige morphologische Veränderungen am Endkolben von Held-Synapsen"],["dc.relation","SFB 1286 | B05: Quantitative molekulare Physiologie aktiver Zonen in Calyx-Synapsen"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.relation.workinggroup","RG Wichmann (Molecular Architecture of Synapses)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","RIM-Binding Protein 2 Promotes a Large Number of CaV1.3 Ca2+-Channels and Contributes to Fast Synaptic Vesicle Replenishment at Hair Cell Active Zones"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]