Sigrist, Stephan J.

[["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences of the United States of America"],["dc.bibliographiccitation.volume","118"],["dc.contributor.author","Fukaya, Ryota"],["dc.contributor.author","Maglione, Marta"],["dc.contributor.author","Sigrist, Stephan J."],["dc.contributor.author","Sakaba, Takeshi"],["dc.date.accessioned","2022-08-19T11:52:31Z"],["dc.date.available","2022-08-19T11:52:31Z"],["dc.date.issued","2021"],["dc.description.abstract","The cyclic adenosine monophosphate (cAMP)-dependent potentiation of neurotransmitter release is important for higher brain functions such as learning and memory. To reveal the underlying mechanisms, we applied paired pre- and postsynaptic recordings from hippocampal mossy fiber-CA3 synapses. Ca2+ uncaging experiments did not reveal changes in the intracellular Ca2+ sensitivity for transmitter release by cAMP, but suggested an increase in the local Ca2+ concentration at the release site, which was much lower than that of other synapses before potentiation. Total internal reflection fluorescence (TIRF) microscopy indicated a clear increase in the local Ca2+ concentration at the release site within 5 to 10 min, suggesting that the increase in local Ca2+ is explained by the simple mechanism of rapid Ca2+ channel accumulation. Consistently, two-dimensional time-gated stimulated emission depletion microscopy (gSTED) microscopy showed an increase in the P/Q-type Ca2+ channel cluster size near the release sites. Taken together, this study suggests a potential mechanism for the cAMP-dependent increase in transmission at hippocampal mossy fiber-CA3 synapses, namely an accumulation of active zone Ca2+ channels."],["dc.identifier.doi","10.1073/pnas.2016754118"],["dc.identifier.pmid","33622791"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113055"],["dc.identifier.url","https://for2705.de/literature/publications/33"],["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","1091-6490"],["dc.relation.issn","0027-8424"],["dc.relation.workinggroup","RG Sigrist (Genetics)"],["dc.title","Rapid Ca2+ channel accumulation contributes to cAMP-mediated increase in transmission at hippocampal mossy fiber synapses"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["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.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","1711.e5"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Current Biology"],["dc.bibliographiccitation.lastpage","1725.e5"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Ramesh, Niraja"],["dc.contributor.author","Escher, Marc J. F."],["dc.contributor.author","Mampell, Malou M."],["dc.contributor.author","Böhme, Mathias A."],["dc.contributor.author","Götz, Torsten W. B."],["dc.contributor.author","Goel, Pragya"],["dc.contributor.author","Matkovic, Tanja"],["dc.contributor.author","Petzoldt, Astrid G."],["dc.contributor.author","Dickman, Dion"],["dc.contributor.author","Sigrist, Stephan J."],["dc.date.accessioned","2022-08-19T11:56:00Z"],["dc.date.available","2022-08-19T11:56:00Z"],["dc.date.issued","2021"],["dc.description.abstract","As a result of developmental synapse formation, the presynaptic neurotransmitter release machinery becomes accurately matched with postsynaptic neurotransmitter receptors. Trans-synaptic signaling is executed through cell adhesion proteins such as Neurexin::Neuroligin pairs but also through diffusible and cytoplasmic signals. How exactly pre-post coordination is ensured in vivo remains largely enigmatic. Here, we identified a \"molecular choreography\" coordinating pre- with postsynaptic assembly during the developmental formation of Drosophila neuromuscular synapses. Two presynaptic Neurexin-binding scaffold proteins, Syd-1 and Spinophilin (Spn), spatio-temporally coordinated pre-post assembly in conjunction with two postsynaptically operating, antagonistic Neuroligin species: Nlg1 and Nlg2. The Spn/Nlg2 module promoted active zone (AZ) maturation by driving the accumulation of AZ scaffold proteins critical for synaptic vesicle release. Simultaneously, these regulators restricted postsynaptic glutamate receptor incorporation. Both functions of the Spn/Nlg2 module were directly antagonized by Syd-1/Nlg1. Nlg1 and Nlg2 also had divergent effects on Nrx-1 in vivo motility. Concerning diffusible signals, Spn and Syd-1 antagonistically controlled the levels of Munc13-family protein Unc13B at nascent AZs, whose release function facilitated glutamate receptor incorporation at assembling postsynaptic specializations. As a result, we here provide direct in vivo evidence illustrating how a highly regulative and interleaved communication between cell adhesion protein signaling complexes and diffusible signals allows for a precise coordination of pre- with postsynaptic assembly. It will be interesting to analyze whether this logic also transfers to plasticity processes."],["dc.identifier.doi","10.1016/j.cub.2021.01.093"],["dc.identifier.pmid","33651992"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113057"],["dc.identifier.url","https://for2705.de/literature/publications/35"],["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","Antagonistic interactions between two Neuroligins coordinate pre- and postsynaptic assembly"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["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"]]