Funke, Frank

[["dc.bibliographiccitation.firstpage","2395"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Journal of Neurophysiology"],["dc.bibliographiccitation.lastpage","2410"],["dc.bibliographiccitation.volume","101"],["dc.contributor.author","Funke, Frank"],["dc.contributor.author","Kron, Miriam"],["dc.contributor.author","Dutschmann, Mathias"],["dc.contributor.author","Mueller, Michael"],["dc.date.accessioned","2018-11-07T08:30:23Z"],["dc.date.available","2018-11-07T08:30:23Z"],["dc.date.issued","2009"],["dc.description.abstract","Funke F, Kron M, Dutschmann M, Muller M. Infant brain stem is prone to the generation of spreading depression during severe hypoxia. J Neurophysiol 101: 2395-2410, 2009. First published March 4, 2009; doi:10.1152/jn.91260.2008. Spreading depression (SD) resembles a concerted, massive neuronal/glial depolarization propagating within the gray matter. Being associated with cerebropathology, such as cerebral ischemia or hemorrhage, epileptic seizures, and migraine, it is well studied in cortex and hippocampus. We have now analyzed the susceptibility of rat brain stem to hypoxia-induced spreading depression-like depolarization (HSD), which could critically interfere with cardiorespiratory control. In rat brain stem slices, severe hypoxia (oxygen withdrawal) triggered HSD within minutes. The sudden extracellular DC potential shift of approximately -20 mV showed the typical profile known from other brain regions and was accompanied by an intrinsic optical signal (IOS). Spatiotemporal IOS analysis revealed that in infant brain stem, HSD was preferably ignited within the spinal trigeminal nucleus and then mostly spread out medially, invading the hypoglossal nucleus, the nucleus of the solitary tract (NTS), and the ventral respiratory group (VRG). The neuronal hypoxic depolarizations underlying the generation of HSD were massive, but incomplete. The propagation velocity of HSD and the associated extracellular K+ rise were also less marked than in other brain regions. In adult brain stem, HSD was mostly confined to the NTS and its occurrence was facilitated by hypotonic solutions, but not by glial poisoning or block of GABAergic and glycinergic synapses. In conclusion, brain stem tissue reliably generates propagating HSD episodes, which may be of interest for basilar-type migraine and brain stem infarcts. The preferred occurrence of HSD in the infant brain stem and its propagation into the VRG may be of importance for neonatal brain stem pathology such as sudden infant death syndrome."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.1152/jn.91260.2008"],["dc.identifier.isi","000265398100023"],["dc.identifier.pmid","19261708"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16886"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Physiological Soc"],["dc.relation.issn","0022-3077"],["dc.title","Infant Brain Stem Is Prone to the Generation of Spreading Depression During Severe Hypoxia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3067"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of Neurophysiology"],["dc.bibliographiccitation.lastpage","3079"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Kron, Miriam"],["dc.contributor.author","Zimmermann, Jasper L."],["dc.contributor.author","Dutschmann, Mathias"],["dc.contributor.author","Funke, Frank"],["dc.contributor.author","Müller, Michael"],["dc.date.accessioned","2018-09-28T10:28:17Z"],["dc.date.available","2018-09-28T10:28:17Z"],["dc.date.issued","2011"],["dc.description.abstract","Rett syndrome (RTT) patients suffer from respiratory arrhythmias with frequent apneas causing intermittent hypoxia. In a RTT mouse model (methyl-CpG-binding protein 2-deficient mice; Mecp2(-/y)) we recently discovered an enhanced hippocampal susceptibility to hypoxia and hypoxia-induced spreading depression (HSD). In the present study we investigated whether this also applies to infant Mecp2(-/y) brain stem, which could become life-threatening due to failure of cardiorespiratory control. HSD most reliably occurred in the nucleus of the solitary tract (NTS) and the spinal trigeminal nucleus (Sp5). HSD susceptibility of the Mecp2(-/y) NTS and Sp5 was increased on 8 mM K(+)-mediated conditioning. 5-HT(1A) receptor stimulation with 8-hydroxy-2-(di-propylamino)tetralin (8-OH-DPAT) postponed HSD by up to 40%, mediating genotype-independent protection. The deleterious impact of HSD on in vitro respiration became obvious in rhythmically active slices, where HSD propagation into the pre-Bötzinger complex (pre-BötC) immediately arrested the respiratory rhythm. Compared with wild-type, the Mecp2(-/y) pre-BötC was invaded less frequently by HSD, but if so, HSD occurred earlier. On reoxygenation, in vitro rhythms reappeared with increased frequency, which was less pronounced in Mecp2(-/y) slices. 8-OH-DPAT increased respiratory frequency but failed to postpone HSD in the pre-BötC. Repetitive hypoxia facilitated posthypoxic recovery only if HSD occurred. In 57% of Mecp2(-/y) slices, however, HSD spared the pre-BötC. Although this occasionally promoted residual hypoxic respiratory activity (\"gasping\"), it also prolonged the posthypoxic recovery, and thus the absence of central inspiratory drive, which in vivo would lengthen respiratory arrest. In view of the breathing disorders in RTTs, the increased hypoxia susceptibility of MeCP2-deficient brain stem potentially contributes to life-threatening disturbances of cardiorespiratory control."],["dc.identifier.doi","10.1152/jn.00822.2010"],["dc.identifier.pmid","21471397"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15858"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1522-1598"],["dc.title","Altered responses of MeCP2-deficient mouse brain stem to severe hypoxia"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","A369"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The FASEB Journal"],["dc.bibliographiccitation.lastpage","A370"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Funke, Frank"],["dc.contributor.author","Mueller, M."],["dc.contributor.author","Dutschmann, Mathias"],["dc.date.accessioned","2018-11-07T10:07:47Z"],["dc.date.available","2018-11-07T10:07:47Z"],["dc.date.issued","2006"],["dc.identifier.isi","000236206503097"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39346"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Federation Amer Soc Exp Biol"],["dc.publisher.place","Bethesda"],["dc.relation.conference","Experimental Biology 2006 Annual Meeting"],["dc.relation.eventlocation","San Francisco, CA"],["dc.relation.issn","0892-6638"],["dc.title","A novel, more complex rhythmic slice preparation containing the preBotzinger (PBC) and Kolliker-Fuse (KF) region"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","C508"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","AJP Cell Physiology"],["dc.bibliographiccitation.lastpage","C516"],["dc.bibliographiccitation.volume","292"],["dc.contributor.author","Funke, Frank"],["dc.contributor.author","Dutschmann, Mathias"],["dc.contributor.author","Mueller, Michael"],["dc.date.accessioned","2018-11-07T11:05:52Z"],["dc.date.available","2018-11-07T11:05:52Z"],["dc.date.issued","2007"],["dc.description.abstract","The pre-Botzinger complex (PBC) in the rostral ventrolateral medulla contains a kernel involved in respiratory rhythm generation. So far, its respiratory activity has been analyzed predominantly by electrophysiological approaches. Recent advances in fluorescence imaging now allow for the visualization of neuronal population activity in rhythmogenic networks. In the respiratory network, voltage-sensitive dyes have been used mainly, so far, but their low sensitivity prevents an analysis of activity patterns of single neurons during rhythmogenesis. We now have succeeded in using more sensitive Ca2+ imaging to study respiratory neurons in rhythmically active brain stem slices of neonatal rats. For the visualization of neuronal activity, fluo-3 was suited best in terms of neuronal specificity, minimized background fluorescence, and response magnitude. The tissue penetration of fluo-3 was improved by hyperosmolar treatment (100 mM mannitol) during dye loading. Rhythmic population activity was imaged with single-cell resolution using a sensitive charge-coupled device camera and a x20 objective, and it was correlated with extracellularly recorded mass activity of the contralateral PBC. Correlated optical neuronal activity was obvious online in 29% of slices. Rhythmic neurons located deeper became detectable during offline image processing. Based on their activity patterns, 74% of rhythmic neurons were classified as inspiratory and 26% as expiratory neurons. Our approach is well suited to visualize and correlate the activity of several single cells with respiratory network activity. We demonstrate that neuronal synchronization and possibly even network configurations can be analyzed in a noninvasive approach with single-cell resolution and at frame rates currently not reached by most scanning-based imaging techniques."],["dc.identifier.doi","10.1152/ajpcell.00253.2006"],["dc.identifier.isi","000243425900051"],["dc.identifier.pmid","16956966"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/52166"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Physiological Soc"],["dc.relation.issn","0363-6143"],["dc.title","Imaging of respiratory-related population activity with single-cell resolution"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","185"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Pflügers Archiv - European Journal of Physiology"],["dc.bibliographiccitation.lastpage","195"],["dc.bibliographiccitation.volume","457"],["dc.contributor.author","Funke, Frank"],["dc.contributor.author","Mueller, Michael"],["dc.contributor.author","Dutschmann, Mathias"],["dc.date.accessioned","2018-11-07T11:10:46Z"],["dc.date.available","2018-11-07T11:10:46Z"],["dc.date.issued","2008"],["dc.description.abstract","Recent studies showed that respiratory rhythm generation depends on oscillators located in the pre-Botzinger complex (pre-BotC) and the parafacial respiratory group (pFRG). To study inhibitory synaptic interactions between these two oscillators, we developed a rostrally tilted transversal slice preparation, which preserves these regions. The onset of rhythmic mass activity in the retrotrapezoid nucleus (RTN)/pFRG preceded that of the pre-BotC. Blockade of glycinergic and gamma-aminobutyric acidic inhibition synchronized preBotC and RTN/pFRG activity and significantly increased preBotC burst frequency, amplitude, and duration. Population imaging revealed recruitment of inspiratory-like neurones, while expiratory-like neurones lost their phasic activity. The reconfiguration after disinhibition reveals: (1) synaptic inhibition of the pre-BotC arising from the RTN/pFRG, (2) excitatory drive from the RTN/pFRG that triggers the pre-BotC burst. Our findings support the view that these synaptic interactions in vitro relate to the initiation of the inspiratory phase or to the steering of the expiratory-inspiratory phase transition in vivo."],["dc.identifier.doi","10.1007/s00424-008-0509-2"],["dc.identifier.isi","000259373000016"],["dc.identifier.pmid","18458944"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?goescholar/3069"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53280"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0031-6768"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Reconfiguration of respiratory-related population activity in a rostrally tilted transversal slice preparation following blockade of inhibitory neurotransmission in neonatal rats"],["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.issue","4"],["dc.bibliographiccitation.journal","The FASEB Journal"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Funke, Frank"],["dc.contributor.author","Dutschmann, Mathias"],["dc.contributor.author","Mueller, M."],["dc.date.accessioned","2018-11-07T10:07:51Z"],["dc.date.available","2018-11-07T10:07:51Z"],["dc.date.issued","2006"],["dc.format.extent","A369"],["dc.identifier.isi","000236206503096"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39357"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Federation Amer Soc Exp Biol"],["dc.publisher.place","Bethesda"],["dc.relation.conference","Experimental Biology 2006 Annual Meeting"],["dc.relation.eventlocation","San Francisco, CA"],["dc.relation.issn","0892-6638"],["dc.title","Imaging of respiratory population activity in the rat preBotzinger region (PBC) with single cell resolution"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","S292"],["dc.bibliographiccitation.journal","Journal of Cerebral Blood Flow & Metabolism"],["dc.bibliographiccitation.lastpage","S293"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Mueller, M."],["dc.contributor.author","Kron, Martina"],["dc.contributor.author","Dutschmann, Mathias"],["dc.contributor.author","Funke, Frank"],["dc.date.accessioned","2018-11-07T11:23:50Z"],["dc.date.available","2018-11-07T11:23:50Z"],["dc.date.issued","2009"],["dc.identifier.isi","000270329900354"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56273"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.publisher.place","New york"],["dc.relation.conference","24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET"],["dc.relation.eventlocation","Chicago, IL"],["dc.relation.issn","0271-678X"],["dc.title","Infant brainstem is prone to the generation of spreading depression during severe hypoxia"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]