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","226"],["dc.bibliographiccitation.issue","5630"],["dc.bibliographiccitation.journal","Science"],["dc.bibliographiccitation.lastpage","229"],["dc.bibliographiccitation.volume","301"],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Guenther, U."],["dc.contributor.author","Ponimaskin, Evgeni G."],["dc.contributor.author","Haller, M."],["dc.contributor.author","Dutschmann, Mathias"],["dc.contributor.author","Schwarzacher, S."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T10:37:41Z"],["dc.date.available","2018-11-07T10:37:41Z"],["dc.date.issued","2003"],["dc.description.abstract","Opiates are widely used analgesics in anesthesiology, but they have serious adverse effects such as depression of breathing. This is caused by direct inhibition of rhythm-generating respiratory neurons in the Pre-Boetzinger complex (PBC) of the brainstem. We report that serotonin 4(a) [5-HT4(a)] receptors are strongly expressed in respiratory PBC neurons and that their selective activation protects spontaneous respiratory activity. Treatment of rats with a 5-HT4 receptor specific agonist overcame fentanyl-induced respiratory depression and reestablished stable respiratory rhythm without loss of fentanyl's analgesic effect. These findings imply the prospect of a fine-tuned recovery from opioid-induced respiratory depression, through adjustment of intracellular adenosine 3', 5'-monophosphate levels through the convergent signaling pathways in neurons."],["dc.identifier.doi","10.1126/science.1084674"],["dc.identifier.isi","000184056200047"],["dc.identifier.pmid","12855812"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45628"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Advancement Science"],["dc.relation.issn","0036-8075"],["dc.title","5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","542"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Trends in Molecular Medicine"],["dc.bibliographiccitation.lastpage","548"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Richter, Diethelm W."],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Wilken, Barbara"],["dc.contributor.author","Ponimaskin, Evgeni G."],["dc.date.accessioned","2018-11-07T10:34:35Z"],["dc.date.available","2018-11-07T10:34:35Z"],["dc.date.issued","2003"],["dc.description.abstract","Disturbances of breathing arising from failures of the respiratory center are not uncommon. Among them, breath holding and apnea occur most frequently as consequences of pulmonary and cardiac diseases, hypoxia, head trauma, cerebral inflammatory processes, genetic defects, degenerative brain diseases, alcoholism, deep anesthesia and drug overdose. They are often life-threatening and fail to respond to existing pharmacotherapies. After extensive research, there is now a reliable basis for new strategies to treat respiratory disturbances by pharmacological manipulation of intracellular signaling pathways, particularly those involving the serotonin receptor family. Specific activation of these pathways effectively prevails respiratory disturbances and can be extended to treatment of life-threatening respiratory disorders in patients."],["dc.identifier.doi","10.1016/j.molmed.2003.10.010"],["dc.identifier.isi","000187575100008"],["dc.identifier.pmid","14659469"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44908"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Sci Ltd"],["dc.relation.issn","1471-4914"],["dc.title","Serotonin receptors: guardians of stable breathing"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","775"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","The Journal of Comparative Neurology"],["dc.bibliographiccitation.lastpage","790"],["dc.bibliographiccitation.volume","506"],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Preusse, Stefan"],["dc.contributor.author","Huelsmann, Swen"],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T11:18:20Z"],["dc.date.available","2018-11-07T11:18:20Z"],["dc.date.issued","2008"],["dc.description.abstract","Serotonin receptors (5-HTRs) are known to be involved in the regulation of breathing behavior and to mediate neurotrophic actions that exert a significant function in network formation during development. We studied neuronal 5-HT4(a)R-immunoreactivity (-IR) at developmental ages from E14 to P10. Within the pre-Botzinger complex (pre-BotC), a part of the respiratory network important for rhythmogenesis, 5-HT4(a)R-IR was most extensive in rats at an age of E18. The 5-HT4(a)-IR was found predominantly in the neuropil, whereas somatic staining was sporadic at late embryonic (E18-E20) stages. At birth, we observed a dramatic change to a predominantly somatic staining, and neuropil staining was greatly reduced and disappeared at an age of P4. In all developmental stages, 5-HT4(a) and mu-opioid receptors were strongly coexpressed in neurons of the pre-BotC, whereas 5-HT4(a)R expression was absent in neurons within the dorsal horn. Nestin, a marker for CNS progenitor cells, was used to obtain information about the degree of pre-BotC differentiation. Nestin-positive cells did not appear within the pre-BotC before age E20. At E16, nestin-expressing cells were absent in the nucleus ambiguus (NA) and its ventral periphery. The number of nestin-positive cells increased after birth within and outside the pre-BotC, the majority of cells being glial. Coexpression of nestin and 5-HT4(a)R was localized predominantly within the NA and appeared only sporadically within the pre-BotC. We conclude that 5-HT(4(a))Rs are important not only for neuromodulation of cellular excitability but also for respiratory network formation."],["dc.identifier.doi","10.1002/cne.21581"],["dc.identifier.isi","000252334500003"],["dc.identifier.pmid","18076058"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/55012"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.relation.issn","0021-9967"],["dc.title","Developmental changes of serotonin 4(a) receptor expression in the rat pre-Botzinger complex"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1276"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","European Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","1291"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Shevtsova, Natalia A."],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Molkov, Yaroslav I."],["dc.contributor.author","Bischoff, Anne M."],["dc.contributor.author","Smith, Jeffrey C."],["dc.contributor.author","Rybak, Ilya A."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T08:50:56Z"],["dc.date.available","2018-11-07T08:50:56Z"],["dc.date.issued","2011"],["dc.description.abstract","Brainstem respiratory neurons express the glycine a3 receptor (Glya3R), which is a target of modulation by several serotonin (5-HT) receptor agonists. Application of the 5-HT1A receptor (5-HT1AR) agonist 8-OH-DPAT was shown (i) to depress cellular cAMP, leading to dephosphorylation of Glya3R and augmentation of postsynaptic inhibition of neurons expressing Glya3R (Manzke , 2010) and (ii) to hyperpolarize respiratory neurons through 5-HT-activated potassium channels. These processes counteract opioid-induced depression and restore breathing from apnoeas often accompanying pharmacotherapy of pain. The effect is postulated to rely on the enhanced Glya3R-mediated inhibition of inhibitory neurons causing disinhibition of their target neurons. To evaluate this proposal and investigate the neural mechanisms involved, an established computational model of the brainstem respiratory network (Smith , 2007), was extended by (i) incorporating distinct subpopulations of inhibitory neurons (glycinergic and GABAergic) and their synaptic interconnections within the Botzinger and pre-Botzinger complexes and (ii) assigning the 5-HT1AR-Glya3R complex to some of these inhibitory neuron types in the network. The modified model was used to simulate the effects of 8-OH-DPAT on the respiratory pattern and was able to realistically reproduce a number of experimentally observed responses, including the shift in the onset of post-inspiratory activity to inspiration and conversion of the eupnoeic three-phase rhythmic pattern into a two-phase pattern lacking the post-inspiratory phase. The model shows how 5-HT1AR activation can produce a disinhibition of inspiratory neurons, leading to the recovery of respiratory rhythm from opioid-induced apnoeas."],["dc.identifier.doi","10.1111/j.1460-9568.2011.07825.x"],["dc.identifier.isi","000297014000011"],["dc.identifier.pmid","21899601"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21810"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0953-816X"],["dc.title","Computational modelling of 5-HT receptor-mediated reorganization of the brainstem respiratory network"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","The FASEB Journal"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Shevtsova, Natalia A."],["dc.contributor.author","Bischoff, Anne M."],["dc.contributor.author","Molkov, Yaroslav I."],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Rybak, Ilya A."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T08:57:49Z"],["dc.date.available","2018-11-07T08:57:49Z"],["dc.date.issued","2011"],["dc.identifier.isi","000310708403961"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23492"],["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 Meeting 2011"],["dc.relation.eventlocation","Washington, DC"],["dc.relation.issn","0892-6638"],["dc.title","Computational Modeling of Serotonin-Evoked Reorganization of the Brain Stem Respiratory Network"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2611"],["dc.bibliographiccitation.issue","1529"],["dc.bibliographiccitation.journal","Philosophical Transactions of The Royal Society B Biological Sciences"],["dc.bibliographiccitation.lastpage","2623"],["dc.bibliographiccitation.volume","364"],["dc.contributor.author","Dutschmann, Mathias"],["dc.contributor.author","Waki, Hidefumi"],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Simms, A. E."],["dc.contributor.author","Pickering, A. E."],["dc.contributor.author","Richter, Diethelm W."],["dc.contributor.author","Paton, Julian F. R."],["dc.date.accessioned","2018-11-07T11:24:20Z"],["dc.date.available","2018-11-07T11:24:20Z"],["dc.date.issued","2009"],["dc.description.abstract","Serotonin receptor (5-HTR) agonists that target 5-HT(4(a))R and 5-HT(1A)R can reverse mu-opioid receptor (mu-OR)-evoked respiratory depression. Here, we have tested whether such rescuing by serotonin agonists also applies to the cardiovascular system. In working heart-brainstem preparations in situ, we have recorded phrenic nerve activity, thoracic sympathetic chain activity (SCA), vascular resistance and heart rate (HR) and in conscious rats, diaphragmatic electromyogram, arterial blood pressure (BP) and HR via radio-telemetry. In addition, the distribution of 5-HT(4(a))R and 5-HT(1A)R in ponto-medullary cardiorespiratory networks was identified using histochemistry. Systemic administration of the mu-OR agonist fentanyl in situ decreased HR, vascular resistance, SCA and phrenic nerve activity. Subsequent application of the 5-HT(1A)R agonist 8-OH-DPAT further enhanced bradycardia, but partially compensated the decrease in vascular resistance, sympathetic activity and restored breathing. By contrast, the 5-HT(4(a))R agonist RS67333 further decreased vascular resistance, HR and sympathetic activity, but partially rescued breathing. In conscious rats, administration of remifentanyl caused severe respiratory depression, a decrease in mean BP accompanied by pronounced bradyarrhythmia. 8-OH-DPAT restored breathing and prevented the bradyarrhythmia; however, BP and HR remained below baseline. In contrast, RS67333 further suppressed cardiovascular functions in vivo and only partially recovered breathing in some cases. The better recovery of mu-OR cardiorespiratory disturbance by 5-HT(1A)R than 5-HT(4(a))R is supported by the finding that 5-HT(1A)R was more densely expressed in key brainstem nuclei for cardiorespiratory control compared with 5-HT(4(a))R. We conclude that during treatment of severe pain, 5-HT(1A)R agonists may provide a useful tool to counteract opioid-mediated cardiorespiratory disturbances."],["dc.description.sponsorship","British Heart Foundation [RG/07/006/23634]; Wellcome Trust [074570]"],["dc.identifier.doi","10.1098/rstb.2009.0076"],["dc.identifier.isi","000268569000016"],["dc.identifier.pmid","19651661"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56379"],["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.title","The potency of different serotonergic agonists in counteracting opioid evoked cardiorespiratory disturbances"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","272"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Der Schmerz"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Niebert, M."],["dc.contributor.author","Koch, Uwe R."],["dc.contributor.author","Caley, Alex"],["dc.contributor.author","Vogelgesang, S."],["dc.contributor.author","Bischoff, A.-M."],["dc.contributor.author","Huelsmann, Swen"],["dc.contributor.author","Ponimaskin, Evgeni G."],["dc.contributor.author","Mueller, U."],["dc.contributor.author","Smart, Trevor G."],["dc.contributor.author","Harvey, R. J."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T08:55:51Z"],["dc.date.available","2018-11-07T08:55:51Z"],["dc.date.issued","2011"],["dc.description.abstract","To control the breathing rhythm the medullary respiratory network generates periodic salvo activities for inspiration, post-inspiration and expiration. These are under permanent modulatory control by serotonergic neurons of the raphe which governs the degree of phosphorylation of the inhibitory glycine receptor alpha 3. The specific activation of serotonin receptor type 1A (5-HTR(1A)), which is strongly expressed in the respiratory neurons, functions via inhibition of adenylate cyclase and the resulting reduction of the intracellular cAMP level and a gradual dephosphorylation of the glycine receptor type alpha 3 (GlyR alpha 3). This 5-HTR(1A)-GlyR alpha 3 signal pathway is independent of the A mu-opioidergic transduction pathway and via a synaptic inhibition caused by an increase in GlyR alpha 3 stimulates a disinhibition of some target neurons not only from excitatory but also from inhibitory neurons. Our physiological investigations show that this 5-HTR(1A)-GlyR alpha 3 modulation allows treatment of respiratory depression due to opioids without affecting the desired analgesic effects of opioids. The molecular mechanism presented here opens new pharmacological possibilities to treat opioid-induced respiratory depression and respiratory disorders due to disturbed inhibitory synaptic transmission, such as hyperekplexia."],["dc.description.sponsorship","Medical Research Council [G0500833]"],["dc.identifier.doi","10.1007/s00482-011-1044-1"],["dc.identifier.isi","000291886200005"],["dc.identifier.pmid","21499860"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23005"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0932-433X"],["dc.title","Serotonin receptor 1A-modulated dephosphorylation of glycine receptor alpha 3. A new molecular mechanism of breathing control for compensation of opioid-induced respiratory depression without loss of analgesia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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"]]

[["dc.bibliographiccitation.firstpage","209"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","European Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","218"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Bickmeyer, U."],["dc.contributor.author","Heine, M."],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T10:20:38Z"],["dc.date.available","2018-11-07T10:20:38Z"],["dc.date.issued","2002"],["dc.description.abstract","CA1 pyramidal neurons of the hippocampus express various types of serotonin (5-HT) receptors, such as 5-HT1A, 5-HT4 and 5-HT7 receptors, which couple to Galpha(i) or Galpha(s) proteins and operate on different intracellular signalling pathways. In the present paper we verify such differential serotonergic modulation for the hyperpolarization-activated current I-h . Activation of 5-HT1A receptors induced an augmentation of current-induced hyperpolarization responses, while the responses declined after 5-HT4 receptors were activated. The resting potential of neurons hyperpolarized (-2.3 +/- 0.7 mV) after 5-HT1A receptor activation, activation of 5-HT4 receptors depolarized neurons (+3.3 +/- 1.4 mV). Direct activation of adenylyl cyclase (AC) by forskolin also produced a depolarization. In voltage clamp, the I-h current was identified by its characteristic voltage- and time-dependency and by blockade with CsCl or ZD7288. Activation of 5-HT1A receptors reduced I-h and shifted the activation curve to a more negative voltage by -5 mV at half-maximal activation. Activation of 5-HT4 and 5-HT7 receptors increased I-h and shifted the activation curve to the right by +5 mV. Specific activation of 5-HT4 receptors by BIMU8 increased membrane conductance and showed an increase in I-h in a subset of cells, but did not induce a significant alteration in the activation curve. In order to verify spatial differences, we applied BIMU8 selectively to the soma and to the dendrites. Only somatic application induced receptor activation. These data are confirmed by immunofluorescence stainings with an antibody against the 5-HT4A receptor, revealing receptor expression at the somata of the CA1 region. A similar expression pattern was found with a new antibody against 5-HT7 receptors which reveals immunofluorescence staining on the cell bodies of pyramidal neurons."],["dc.identifier.doi","10.1046/j.1460-9568.2002.02072.x"],["dc.identifier.isi","000177364000004"],["dc.identifier.pmid","12169103"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41929"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing Ltd"],["dc.relation.issn","0953-816X"],["dc.title","Differential modulation of I-h by 5-HT receptors in mouse CA1 hippocampal neurons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]