Sigrist, Stephan J.

[["dc.bibliographiccitation.firstpage","1077.e5"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Current Biology"],["dc.bibliographiccitation.lastpage","1091.e5"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Huang, Sheng"],["dc.contributor.author","Piao, Chengji"],["dc.contributor.author","Beuschel, Christine B."],["dc.contributor.author","Götz, Torsten"],["dc.contributor.author","Sigrist, Stephan J."],["dc.date.accessioned","2022-08-19T10:05:19Z"],["dc.date.available","2022-08-19T10:05:19Z"],["dc.date.issued","2020"],["dc.description.abstract","Sleep is universal across species and essential for quality of life and health, as evidenced by the consequences of sleep loss. Sleep might homeostatically normalize synaptic gains made over wake states in order to reset information processing and storage and support learning, and sleep-associated synaptic (ultra)structural changes have been demonstrated recently. However, causal relationships between the molecular and (ultra)structural status of synapses, sleep homeostatic regulation, and learning processes have yet to be established. We show here that the status of the presynaptic active zone can directly control sleep in Drosophila. Short sleep mutants showed a brain-wide upregulation of core presynaptic scaffold proteins and release factors. Increasing the gene copy number of ELKS-family scaffold master organizer Bruchpilot (BRP) not only mimicked changes in the active zone scaffold and release proteins but importantly provoked sleep in a dosage-dependent manner, qualitatively and quantitatively reminiscent of sleep deprivation effects. Conversely, reducing the brp copy number decreased sleep in short sleep mutant backgrounds, suggesting a specific role of the active zone plasticity in homeostatic sleep regulation. Finally, elimination of BRP specifically in the sleep-promoting R2 neurons of 4xBRP animals partially restored sleep patterns and rescued learning deficits. Our results suggest that the presynaptic active zone plasticity driven by BRP operates as a sleep homeostatic actuator that also restricts periods of effective learning."],["dc.identifier.doi","10.1016/j.cub.2020.01.019"],["dc.identifier.pmid","32142702"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113043"],["dc.identifier.url","https://for2705.de/literature/publications/13"],["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","1879-0445"],["dc.relation.issn","0960-9822"],["dc.relation.workinggroup","RG Sigrist (Genetics)"],["dc.title","Presynaptic Active Zone Plasticity Encodes Sleep Need in Drosophila"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["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"]]

[["dc.bibliographiccitation.firstpage","106"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neurogenetics"],["dc.bibliographiccitation.lastpage","114"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Woitkuhn, Jennifer"],["dc.contributor.author","Ender, Anatoli"],["dc.contributor.author","Beuschel, Christine B."],["dc.contributor.author","Maglione, Marta"],["dc.contributor.author","Matkovic-Rachid, Tanja"],["dc.contributor.author","Huang, Sheng"],["dc.contributor.author","Lehmann, Martin"],["dc.contributor.author","Geiger, Joerg R. P."],["dc.contributor.author","Sigrist, Stephan J."],["dc.date.accessioned","2022-08-19T10:14:13Z"],["dc.date.available","2022-08-19T10:14:13Z"],["dc.date.issued","2020"],["dc.description.abstract","The cellular analysis of mushroom body (MB)-dependent memory forming processes is far advanced, whereas, the molecular and physiological understanding of their synaptic basis lags behind. Recent analysis of the Drosophila olfactory system showed that Unc13A, a member of the M(Unc13) release factor family, promotes a phasic, high release probability component, while Unc13B supports a slower tonic release component, reflecting their different nanoscopic positioning within individual active zones. We here use STED super-resolution microscopy of MB lobe synapses to show that Unc13A clusters closer to the active zone centre than Unc13B. Unc13A specifically supported phasic transmission and short-term plasticity of Kenyon cell:output neuron synapses, measured by combining electrophysiological recordings of output neurons with optogenetic stimulation. Knockdown of unc13A within Kenyon cells provoked drastic deficits of olfactory aversive short-term and anaesthesia-sensitive middle-term memory. Knockdown of unc13B provoked milder memory deficits. Thus, a low frequency domain transmission component is probably crucial for the proper representation of memory-associated activity patterns, consistent with sparse Kenyon cell activation during memory acquisition and retrieval. Notably, Unc13A/B ratios appeared highly diversified across MB lobes, leaving room for an interplay of activity components in memory encoding and retrieval."],["dc.identifier.doi","10.1080/01677063.2019.1710146"],["dc.identifier.pmid","31980003"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113047"],["dc.identifier.url","https://for2705.de/literature/publications/17"],["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","1563-5260"],["dc.relation.issn","0167-7063"],["dc.relation.workinggroup","RG Sigrist (Genetics)"],["dc.title","The Unc13A isoform is important for phasic release and olfactory memory formation at mushroom body synapses"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]