Sigrist, Stephan J.

[["dc.bibliographiccitation.firstpage","1318"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Bhukel, Anuradha"],["dc.contributor.author","Beuschel, Christine Brigitte"],["dc.contributor.author","Maglione, Marta"],["dc.contributor.author","Lehmann, Martin"],["dc.contributor.author","Juhász, Gabor"],["dc.contributor.author","Madeo, Frank"],["dc.contributor.author","Sigrist, Stephan J."],["dc.date.accessioned","2022-08-19T09:57:31Z"],["dc.date.available","2022-08-19T09:57:31Z"],["dc.date.issued","2019"],["dc.description.abstract","Macroautophagy is an evolutionarily conserved cellular maintenance program, meant to protect the brain from premature aging and neurodegeneration. How neuronal autophagy, usually loosing efficacy with age, intersects with neuronal processes mediating brain maintenance remains to be explored. Here, we show that impairing autophagy in the Drosophila learning center (mushroom body, MB) but not in other brain regions triggered changes normally restricted to aged brains: impaired associative olfactory memory as well as a brain-wide ultrastructural increase of presynaptic active zones (metaplasticity), a state non-compatible with memory formation. Mechanistically, decreasing autophagy within the MBs reduced expression of an NPY-family neuropeptide, and interfering with autocrine NPY signaling of the MBs provoked similar brain-wide metaplastic changes. Our results in an exemplary fashion show that autophagy-regulated signaling emanating from a higher brain integration center can execute high-level control over other brain regions to steer life-strategy decisions such as whether or not to form memories."],["dc.identifier.doi","10.1038/s41467-019-09262-2"],["dc.identifier.pmid","30899013"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113039"],["dc.identifier.url","https://for2705.de/literature/publications/4"],["dc.language.iso","en"],["dc.relation","FOR 2705: Dissection of a Brain Circuit: Structure, Plasticity and Behavioral Function of the Drosophila Mushroom Body"],["dc.relation.issn","2041-1723"],["dc.relation.workinggroup","RG Sigrist (Genetics)"],["dc.rights","CC BY 4.0"],["dc.title","Autophagy within the mushroom body protects from synapse aging in a non-cell autonomous manner"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","798204"],["dc.bibliographiccitation.journal","Frontiers in Synaptic Neuroscience"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Piao, Chengji"],["dc.contributor.author","Sigrist, Stephan J."],["dc.date.accessioned","2022-08-19T12:09:36Z"],["dc.date.available","2022-08-19T12:09:36Z"],["dc.date.issued","2021"],["dc.description.abstract","The so-called active zones at pre-synaptic terminals are the ultimate filtering devices, which couple between action potential frequency and shape, and the information transferred to the post-synaptic neurons, finally tuning behaviors. Within active zones, the release of the synaptic vesicle operates from specialized \"release sites.\" The (M)Unc13 class of proteins is meant to define release sites topologically and biochemically, and diversity between Unc13-type release factor isoforms is suspected to steer diversity at active zones. The two major Unc13-type isoforms, namely, Unc13A and Unc13B, have recently been described from the molecular to the behavioral level, exploiting Drosophila being uniquely suited to causally link between these levels. The exact nanoscale distribution of voltage-gated Ca2+ channels relative to release sites (\"coupling\") at pre-synaptic active zones fundamentally steers the release of the synaptic vesicle. Unc13A and B were found to be either tightly or loosely coupled across Drosophila synapses. In this review, we reported recent findings on diverse aspects of Drosophila Unc13A and B, importantly, their nano-topological distribution at active zones and their roles in release site generation, active zone assembly, and pre-synaptic homeostatic plasticity. We compared their stoichiometric composition at different synapse types, reviewing the correlation between nanoscale distribution of these two isoforms and release physiology and, finally, discuss how isoform-specific release components might drive the functional heterogeneity of synapses and encode discrete behavior."],["dc.identifier.doi","10.3389/fnsyn.2021.798204"],["dc.identifier.pmid","35046788"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113063"],["dc.identifier.url","https://for2705.de/literature/publications/52"],["dc.language.iso","en"],["dc.relation","FOR 2705: Dissection of a Brain Circuit: Structure, Plasticity and Behavioral Function of the Drosophila Mushroom Body"],["dc.relation.issn","1663-3563"],["dc.relation.workinggroup","RG Sigrist (Genetics)"],["dc.rights","CC BY 4.0"],["dc.title","(M)Unc13s in Active Zone Diversity: A Drosophila Perspective"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["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","12"],["dc.contributor.author","Pooryasin, Atefeh"],["dc.contributor.author","Maglione, Marta"],["dc.contributor.author","Schubert, Marco"],["dc.contributor.author","Matkovic-Rachid, Tanja"],["dc.contributor.author","Hasheminasab, Sayed-mohammad"],["dc.contributor.author","Pech, Ulrike"],["dc.contributor.author","Fiala, André"],["dc.contributor.author","Mielke, Thorsten"],["dc.contributor.author","Sigrist, Stephan J."],["dc.date.accessioned","2021-06-01T09:41:40Z"],["dc.date.available","2021-06-01T09:41:40Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract The physical distance between presynaptic Ca 2+ channels and the Ca 2+ sensors triggering the release of neurotransmitter-containing vesicles regulates short-term plasticity (STP). While STP is highly diversified across synapse types, the computational and behavioral relevance of this diversity remains unclear. In the Drosophila brain, at nanoscale level, we can distinguish distinct coupling distances between Ca 2+ channels and the (m)unc13 family priming factors, Unc13A and Unc13B. Importantly, coupling distance defines release components with distinct STP characteristics. Here, we show that while Unc13A and Unc13B both contribute to synaptic signalling, they play distinct roles in neural decoding of olfactory information at excitatory projection neuron (ePN) output synapses. Unc13A clusters closer to Ca 2+ channels than Unc13B, specifically promoting fast phasic signal transfer. Reduction of Unc13A in ePNs attenuates responses to both aversive and appetitive stimuli, while reduction of Unc13B provokes a general shift towards appetitive values. Collectively, we provide direct genetic evidence that release components of distinct nanoscopic coupling distances differentially control STP to play distinct roles in neural decoding of sensory information."],["dc.identifier.doi","10.1038/s41467-021-22180-6"],["dc.identifier.pmid","33771998"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84997"],["dc.identifier.url","https://for2705.de/literature/publications/38"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","FOR 2705: Dissection of a Brain Circuit: Structure, Plasticity and Behavioral Function of the Drosophila Mushroom Body"],["dc.relation","FOR 2705 | TP 5: Postsynaptic receptor plasticity and transsynaptic communication in storage of memory components in the mushroom bodies"],["dc.relation.eissn","2041-1723"],["dc.relation.workinggroup","RG Fiala"],["dc.relation.workinggroup","RG Sigrist (Genetics)"],["dc.rights","CC BY 4.0"],["dc.title","Unc13A and Unc13B contribute to the decoding of distinct sensory information in Drosophila"],["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","108941"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Liang, YongTian"],["dc.contributor.author","Piao, Chengji"],["dc.contributor.author","Beuschel, Christine B."],["dc.contributor.author","Toppe, David"],["dc.contributor.author","Kollipara, Laxmikanth"],["dc.contributor.author","Bogdanow, Boris"],["dc.contributor.author","Maglione, Marta"],["dc.contributor.author","Lützkendorf, Janine"],["dc.contributor.author","See, Jason Chun Kit"],["dc.contributor.author","Huang, Sheng"],["dc.contributor.author","Conrad, Tim O. F."],["dc.contributor.author","Kintscher, Ulrich"],["dc.contributor.author","Madeo, Frank"],["dc.contributor.author","Liu, Fan"],["dc.contributor.author","Sickmann, Albert"],["dc.contributor.author","Sigrist, Stephan J."],["dc.date.accessioned","2022-08-19T11:57:50Z"],["dc.date.available","2022-08-19T11:57:50Z"],["dc.date.issued","2021"],["dc.description.abstract","Mitochondrial function declines during brain aging and is suspected to play a key role in age-induced cognitive decline and neurodegeneration. Supplementing levels of spermidine, a body-endogenous metabolite, has been shown to promote mitochondrial respiration and delay aspects of brain aging. Spermidine serves as the amino-butyl group donor for the synthesis of hypusine (Nε-[4-amino-2-hydroxybutyl]-lysine) at a specific lysine residue of the eukaryotic translation initiation factor 5A (eIF5A). Here, we show that in the Drosophila brain, hypusinated eIF5A levels decline with age but can be boosted by dietary spermidine. Several genetic regimes of attenuating eIF5A hypusination all similarly affect brain mitochondrial respiration resembling age-typical mitochondrial decay and also provoke a premature aging of locomotion and memory formation in adult Drosophilae. eIF5A hypusination, conserved through all eukaryotes as an obviously critical effector of spermidine, might thus be an important diagnostic and therapeutic avenue in aspects of brain aging provoked by mitochondrial decline."],["dc.identifier.doi","10.1016/j.celrep.2021.108941"],["dc.identifier.pmid","33852845"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113058"],["dc.identifier.url","https://for2705.de/literature/publications/36"],["dc.language.iso","en"],["dc.relation","FOR 2705: Dissection of a Brain Circuit: Structure, Plasticity and Behavioral Function of the Drosophila Mushroom Body"],["dc.relation","FOR 2705 | TP 5: Postsynaptic receptor plasticity and transsynaptic communication in storage of memory components in the mushroom bodies"],["dc.relation.eissn","2211-1247"],["dc.relation.workinggroup","RG Sigrist (Genetics)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.title","eIF5A hypusination, boosted by dietary spermidine, protects from premature brain aging and mitochondrial dysfunction"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]