Manzke, Till U.

[["dc.bibliographiccitation.firstpage","4118"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Journal of Clinical Investigation"],["dc.bibliographiccitation.lastpage","4128"],["dc.bibliographiccitation.volume","120"],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Niebert, Marcus"],["dc.contributor.author","Koch, Uwe R."],["dc.contributor.author","Caley, Alex"],["dc.contributor.author","Vogelgesang, Steffen"],["dc.contributor.author","Huelsmann, Swen"],["dc.contributor.author","Ponimaskin, Evgeni G."],["dc.contributor.author","Mueller, Ulrike"],["dc.contributor.author","Smart, Trevor G."],["dc.contributor.author","Harvey, Robert J."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T08:37:37Z"],["dc.date.available","2018-11-07T08:37:37Z"],["dc.date.issued","2010"],["dc.description.abstract","Rhythmic breathing movements originate from a dispersed neuronal network in the medulla and pons. Here, we demonstrate that rhythmic activity of this respiratory network is affected by the phosphorylation status of the inhibitory glycine receptor alpha 3 subtype (GlyR alpha 3), which controls glutamatergic and glycinergic neuronal discharges, subject to serotonergic modulation. Serotonin receptor type 1A-specific (5-HTR(1A)-specific) modulation directly induced dephosphorylation of GlyR alpha 3 receptors, which augmented inhibitory glycine-activated chloride currents in HEK293 cells coexpressing 5-HTR(1A) and GlyR alpha 3. The 5-HTR(1A)-GlyR alpha 3 signaling pathway was distinct from opioid receptor signaling and efficiently counteracted opioid-induced depression of breathing and consequential apnea in mice. Paradoxically, this rescue of breathing originated from enhanced glycinergic synaptic inhibition of glutamatergic and glycinergic neurons and caused disinhibition of their target neurons. Together, these effects changed respiratory phase alternations and ensured rhythmic breathing in vivo. GlyR alpha 3-deficient mice had an irregular respiratory rhythm under baseline conditions, and systemic 5-HTR(1A) activation failed to remedy opioid-induced respiratory depression in these mice. Delineation of this 5-HTR(1A)-GlyR alpha 3 signaling pathway offers a mechanistic basis for pharmacological treatment of opioid-induced apnea and other breathing disturbances caused by disorders of inhibitory synaptic transmission, such as hyperekplexia, hypoxia/ischemia, and brainstem infarction."],["dc.identifier.doi","10.1172/JCI43029"],["dc.identifier.isi","000283621800043"],["dc.identifier.pmid","20978350"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6108"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18577"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Clinical Investigation Inc"],["dc.relation.issn","0021-9738"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Serotonin receptor 1A-modulated phosphorylation of glycine receptor alpha 3 controls breathing in mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2589"],["dc.bibliographiccitation.issue","1529"],["dc.bibliographiccitation.journal","Philosophical Transactions of The Royal Society B Biological Sciences"],["dc.bibliographiccitation.lastpage","2602"],["dc.bibliographiccitation.volume","364"],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Dutschmann, Mathias"],["dc.contributor.author","Schlaf, Gerald"],["dc.contributor.author","Moerschel, Michael"],["dc.contributor.author","Koch, Uwe R."],["dc.contributor.author","Ponimaskin, Evgeni G."],["dc.contributor.author","Bidon, Olivier"],["dc.contributor.author","Lalley, Peter M."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T11:24:20Z"],["dc.date.available","2018-11-07T11:24:20Z"],["dc.date.issued","2009"],["dc.description.abstract","The cellular effects of serotonin (5-HT), a neuromodulator with widespread influences in the central nervous system, have been investigated. Despite detailed knowledge about the molecular biology of cellular signalling, it is not possible to anticipate the responses of neuronal networks to a global action of 5-HT. Heterogeneous expression of various subtypes of serotonin receptors (5-HTR) in a variety of neurons differently equipped with cell-specific transmitter receptors and ion channel assemblies can provoke diverse cellular reactions resulting in various forms of network adjustment and, hence, motor behaviour. Using the respiratory network as a model for reciprocal synaptic inhibition, we demonstrate that 5-HT(1A)R modulation primarily affects inhibition through glycinergic synapses. Potentiation of glycinergic inhibition of both excitatory and inhibitory neurons induces a functional reorganization of the network leading to a characteristic change of motor output. The changes in network operation are robust and help to overcome opiate-induced respiratory depression. Hence, 5-HT(1A)R activation stabilizes the rhythmicity of breathing during opiate medication of pain."],["dc.identifier.doi","10.1098/rstb.2009.0068"],["dc.identifier.isi","000268569000014"],["dc.identifier.pmid","19651659"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6127"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56378"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Royal Soc"],["dc.publisher.place","London"],["dc.relation.conference","Royal-Society Discussion Meeting on Brainstem - Neural Networks Vital for Life"],["dc.relation.eventlocation","Royal Soc, London, ENGLAND"],["dc.relation.issn","0962-8436"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Serotonin targets inhibitory synapses to induce modulation of network functions"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]