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","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.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"]]