Hirrlinger, Johannes

[["dc.bibliographiccitation.firstpage","1229"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","European Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","1241"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Rahman, Jamilur"],["dc.contributor.author","Latal, A. Tobias"],["dc.contributor.author","Besser, Stefanie"],["dc.contributor.author","Hirrlinger, Johannes"],["dc.contributor.author","Huelsmann, Swen"],["dc.date.accessioned","2018-11-07T09:26:26Z"],["dc.date.available","2018-11-07T09:26:26Z"],["dc.date.issued","2013"],["dc.description.abstract","Inhibitory neurons are involved in the generation and patterning of the respiratory rhythm in the adult animal. However, the role of glycinergic neurons in the respiratory rhythm in the developing network is still not understood. Although the complete loss of glycinergic transmission in vivo is lethal, the blockade of glycinergic transmission in slices of the medulla has little effect on pre-Botzinger complex network activity. As 50% of the respiratory rhythmic neurons in this slice preparation are glycinergic, they have to be considered as integrated parts of the network. We aimed to investigate whether glycinergic neurons receive mixed miniature inhibitory postsynaptic currents (mIPSCs) that result from co-release of GABA and glycine. Quantification of mixed mIPSCs by the use of different objective detection methods resulted in a wide range of results. Therefore, we generated traces of mIPSCs with a known distribution of mixed mIPSCs and mono-transmitter-induced mIPSCs, and tested the detection methods on the simulated data. We found that analysis paradigms, which are based on fitting the sum of two mIPSC templates, to be most acceptable. On the basis of these protocols, 2040% of all mIPSCs recorded from respiratory glycinergic neurons are mixed mIPSCs that result from co-release of GABA and glycine. Furthermore, single-cell reverse transcriptase polymerase chain reaction revealed that 46% of glycinergic neurons co-express mRNA of glycine transporter 2 together with at least one marker protein of GABAergic neurons. Our data suggest that significant co-transmission occurs in the pre-Botzinger complex that might be involved in the shaping of synaptic inhibition of respiratory glycinergic neurons."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft (DFG) [HI1414/2-1, HU797/7-1]; CMPB"],["dc.identifier.doi","10.1111/ejn.12136"],["dc.identifier.isi","000317850800003"],["dc.identifier.pmid","23347272"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30298"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0953-816X"],["dc.title","Mixed miniature postsynaptic currents resulting from co-release of glycine and GABA recorded from glycinergic neurons in the neonatal respiratory network"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0129934"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Besser, Stefanie"],["dc.contributor.author","Sicker, Marit"],["dc.contributor.author","Marx, Grit"],["dc.contributor.author","Winkler, Ulrike"],["dc.contributor.author","Eulenburg, Volker"],["dc.contributor.author","Huelsmann, Swen"],["dc.contributor.author","Hirrlinger, Johannes"],["dc.date.accessioned","2018-11-07T09:55:52Z"],["dc.date.available","2018-11-07T09:55:52Z"],["dc.date.issued","2015"],["dc.description.abstract","GABAergic inhibitory neurons are a large population of neurons in the central nervous system (CNS) of mammals and crucially contribute to the function of the circuitry of the brain. To identify specific cell types and investigate their functions labelling of cell populations by transgenic expression of fluorescent proteins is a powerful approach. While a number of mouse lines expressing the green fluorescent protein (GFP) in different subpopulations of GABAergic cells are available, GFP expressing mouse lines are not suitable for either crossbreeding to other mouse lines expressing GFP in other cell types or for Ca2+-imaging using the superior green Ca2+-indicator dyes. Therefore, we have generated a novel transgenic mouse line expressing the red fluorescent protein tdTomato in GABAergic neurons using a bacterial artificial chromosome based strategy and inserting the tdTomato open reading frame at the start codon within exon 1 of the GAD2 gene encoding glutamic acid decarboxylase 65 (GAD65). TdTomato expression was observed in all expected brain regions; however, the fluorescence intensity was highest in the olfactory bulb and the striatum. Robust expression was also observed in cortical and hippocampal neurons, Purkinje cells in the cerebellum, amacrine cells in the retina as well as in cells migrating along the rostral migratory stream. In cortex, hippocampus, olfactory bulb and brainstem, 80% to 90% of neurons expressing endogenous GAD65 also expressed the fluorescent protein. Moreover, almost all tdTomato-expressing cells coexpressed GAD65, indicating that indeed only GABAergic neurons are labelled by tdTomato expression. This mouse line with its unique spectral properties for labelling GABAergic neurons will therefore be a valuable new tool for research addressing this fascinating cell type."],["dc.description.sponsorship","\"Deutsche Forschungsgemeinschaft\" (DFG) [HI1414/2-1, HU797/7-1]"],["dc.identifier.doi","10.1371/journal.pone.0129934"],["dc.identifier.isi","000356329900114"],["dc.identifier.pmid","26076353"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11956"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36843"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","A Transgenic Mouse Line Expressing the Red Fluorescent Protein tdTomato in GABAergic Neurons"],["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","1"],["dc.bibliographiccitation.journal","Brain Structure and Function"],["dc.bibliographiccitation.lastpage","26"],["dc.contributor.author","Rahman, Jamilur"],["dc.contributor.author","Besser, Stefanie"],["dc.contributor.author","Schnell, Christian"],["dc.contributor.author","Eulenburg, Volker"],["dc.contributor.author","Hirrlinger, Johannes"],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Hülsmann, Swen"],["dc.date.accessioned","2019-07-09T11:41:21Z"],["dc.date.available","2019-07-09T11:41:21Z"],["dc.date.issued","2014"],["dc.description.abstract","Both glycinergic and GABAergic neurons require the vesicular inhibitory amino acid transporter (VIAAT) for synaptic vesicle filling. Presynaptic GABA concentrations are determined by the GABA synthesizing enzymes glutamate decarboxylase (GAD)65 and GAD67, whereas the presynaptic glycine content depends on the plasma membrane glycine transporter 2 (GlyT2). Although severely impaired, glycinergic transmission is not completely absent in GlyT2-knockout mice, suggesting that other routes of glycine uptake or de novo synthesis of glycine exist in presynaptic terminals. To investigate the consequences of a complete loss of glycinergic transmission, we generated a mouse line with a conditional ablation of VIAAT in glycinergic neurons by crossing mice with loxP-flanked VIAAT alleles with a GlyT2-Cre transgenic mouse line. Interestingly, conditional VIAAT knockout (VIAAT cKO) mice were not viable at birth. In addition to the dominant respiratory failure, VIAAT cKO showed an umbilical hernia and a cleft palate. Immunohistochemistry revealed an almost complete depletion of VIAAT in the brainstem. Electrophysiology revealed the absence of both spontaneous glycinergic and GABAergic inhibitory postsynaptic currents (IPSCs) from hypoglossal motoneurons. Our results demonstrate that the deletion of VIAAT in GlyT2-Cre expressing neurons also strongly affects GABAergic transmission and suggest a large overlap of the glycinergic and the GABAergic neuron population during early development in the caudal parts of the brain."],["dc.identifier.doi","10.1007/s00429-014-0829-2"],["dc.identifier.pmid","25027639"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11988"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58409"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Genetic ablation of VIAAT in glycinergic neurons causes a severe respiratory phenotype and perinatal death"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","submitted_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Cellular Neuroscience"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Hirrlinger, Johannes"],["dc.contributor.author","Marx, Grit"],["dc.contributor.author","Besser, Stefanie"],["dc.contributor.author","Sicker, Marit"],["dc.contributor.author","Köhler, Susanne"],["dc.contributor.author","Hirrlinger, Petra G."],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Eulenburg, Volker"],["dc.contributor.author","Winkler, Ulrike"],["dc.contributor.author","Hülsmann, Swen"],["dc.date.accessioned","2020-12-10T18:44:31Z"],["dc.date.available","2020-12-10T18:44:31Z"],["dc.date.issued","2019"],["dc.description.abstract","Inhibitory neurons crucially contribute to shaping the breathing rhythm in the brain stem. These neurons use GABA or glycine as neurotransmitter; or co-release GABA and glycine. However, the developmental relationship between GABAergic, glycinergic and cotransmitting neurons, and the functional relevance of cotransmitting neurons has remained enigmatic. Transgenic mice expressing fluorescent markers or the split-Cre system in inhibitory neurons were developed to track the three different interneuron phenotypes. During late embryonic development, the majority of inhibitory neurons in the ventrolateral medulla are cotransmitting cells, most of which differentiate into GABAergic and glycinergic neurons around birth and around postnatal day 4, respectively. Functional inactivation of cotransmitting neurons revealed an increase of the number of respiratory pauses, the cycle-by-cycle variability, and the overall variability of breathing. In summary, the majority of cotransmitting neurons differentiate into GABAergic or glycinergic neurons within the first 2 weeks after birth and these neurons contribute to fine-tuning of the breathing pattern."],["dc.identifier.doi","10.3389/fncel.2019.00517"],["dc.identifier.eissn","1662-5102"],["dc.identifier.pmid","31803026"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17103"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78488"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1662-5102"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","GABA-Glycine Cotransmitting Neurons in the Ventrolateral Medulla: Development and Functional Relevance for Breathing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]