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000181223 0247_ $$2doi$$a10.1523/JNEUROSCI.2161-17.2017
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000181223 041__ $$aEnglish
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000181223 1001_ $$aGrund, Thomas$$b0
000181223 245__ $$aNeuropeptide S Activates Paraventricular Oxytocin Neurons to Induce Anxiolysis.
000181223 260__ $$aWashington, DC$$bSoc.$$c2017
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000181223 520__ $$aNeuropeptides, such as neuropeptide S (NPS) and oxytocin (OXT), represent potential options for the treatment of anxiety disorders due to their potent anxiolytic profile. In this study, we aimed to reveal the mechanisms underlying the behavioral action of NPS, and present a chain of evidence that the effects of NPS within the hypothalamic paraventricular nucleus (PVN) are mediated via actions on local OXT neurons in male Wistar rats. First, retrograde studies identified NPS fibers originating in the brainstem locus coeruleus, and projecting to the PVN. FACS identified prominent NPS receptor expression in PVN-OXT neurons. Using genetically encoded calcium indicators, we further demonstrated that NPS reliably induces a transient increase in intracellular Ca2+ concentration in a subpopulation of OXT neurons, an effect mediated by NPS receptor. In addition, intracerebroventricular (i.c.v.) NPS evoked a significant somatodendritic release of OXT within the PVN as assessed by microdialysis in combination with a highly sensitive radioimmunoassay. Finally, we could show that the anxiolytic effect of NPS seen after i.c.v. or intra-PVN infusion requires responsive OXT neurons of the PVN and locally released OXT. Thus, pharmacological blockade of OXT receptors as well as chemogenetic silencing of OXT neurons within the PVN prevented the effect of synthetic NPS. In conclusion, our results indicate a significant role of the OXT system in mediating the effects of NPS on anxiety, and fill an important gap in our understanding of brain neuropeptide interactions in the context of regulation of emotional behavior within the hypothalamus.SIGNIFICANCE STATEMENT Given the rising scientific interest in neuropeptide research in the context of emotional and stress-related behaviors, our findings demonstrate a novel intrahypothalamic mechanism involving paraventricular oxytocin neurons that express the neuropeptide S receptor. These neurons respond with transient Ca2+ increase and somatodendritic oxytocin release following neuropeptide S stimulation. Thereby, oxytocin neurons seem essential for neuropeptide S-induced anxiolysis, as this effect was blocked by pharmacological and chemogenetic inhibition of the oxytocin system.
000181223 536__ $$0G:(DE-HGF)POF3-311$$a311 - Signalling pathways, cell and tumor biology (POF3-311)$$cPOF3-311$$fPOF III$$x0
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000181223 650_7 $$2Other$$aDREADD
000181223 650_7 $$2Other$$aGCaMP6s
000181223 650_7 $$2Other$$aanxiety
000181223 650_7 $$2Other$$amicrodialysis
000181223 650_7 $$2Other$$aneuropeptide S
000181223 650_7 $$2Other$$aoxytocin
000181223 650_7 $$2NLM Chemicals$$aBacterial Proteins
000181223 650_7 $$2NLM Chemicals$$aLuminescent Proteins
000181223 650_7 $$2NLM Chemicals$$aNeuropeptides
000181223 650_7 $$2NLM Chemicals$$aReceptors, Neuropeptide
000181223 650_7 $$2NLM Chemicals$$aReceptors, Oxytocin
000181223 650_7 $$2NLM Chemicals$$aneuropeptide S receptor, rat
000181223 650_7 $$2NLM Chemicals$$aneuropeptide S, rat
000181223 650_7 $$2NLM Chemicals$$aoxytocin receptor, rat
000181223 650_7 $$2NLM Chemicals$$ared fluorescent protein
000181223 650_7 $$2NLM Chemicals$$ayellow fluorescent protein, Bacteria
000181223 650_7 $$050-56-6$$2NLM Chemicals$$aOxytocin
000181223 650_2 $$2MeSH$$aAnimals
000181223 650_2 $$2MeSH$$aAnxiety: physiopathology
000181223 650_2 $$2MeSH$$aAxonal Transport
000181223 650_2 $$2MeSH$$aBacterial Proteins: analysis
000181223 650_2 $$2MeSH$$aCalcium Signaling: physiology
000181223 650_2 $$2MeSH$$aDependovirus: genetics
000181223 650_2 $$2MeSH$$aExploratory Behavior: drug effects
000181223 650_2 $$2MeSH$$aGenes, Reporter
000181223 650_2 $$2MeSH$$aGenetic Vectors
000181223 650_2 $$2MeSH$$aLuminescent Proteins: analysis
000181223 650_2 $$2MeSH$$aMale
000181223 650_2 $$2MeSH$$aMicrodialysis
000181223 650_2 $$2MeSH$$aMotor Activity: drug effects
000181223 650_2 $$2MeSH$$aNeuropeptides: pharmacology
000181223 650_2 $$2MeSH$$aNeuropeptides: physiology
000181223 650_2 $$2MeSH$$aOxytocin: agonists
000181223 650_2 $$2MeSH$$aOxytocin: physiology
000181223 650_2 $$2MeSH$$aParaventricular Hypothalamic Nucleus: drug effects
000181223 650_2 $$2MeSH$$aParaventricular Hypothalamic Nucleus: physiology
000181223 650_2 $$2MeSH$$aRats
000181223 650_2 $$2MeSH$$aRats, Wistar
000181223 650_2 $$2MeSH$$aReceptors, Neuropeptide: drug effects
000181223 650_2 $$2MeSH$$aReceptors, Neuropeptide: physiology
000181223 650_2 $$2MeSH$$aReceptors, Oxytocin: antagonists & inhibitors
000181223 650_2 $$2MeSH$$aReceptors, Oxytocin: physiology
000181223 650_2 $$2MeSH$$aSynaptic Transmission: drug effects
000181223 7001_ $$aGoyon, Stephanie$$b1
000181223 7001_ $$0P:(DE-He78)262728a22f16ad48aa602f831de92936$$aLi, Yuting$$b2
000181223 7001_ $$aEliava, Marina$$b3
000181223 7001_ $$0P:(DE-He78)76aeb2431f7458c9261e69c5420390c6$$aLiu, Haikun$$b4$$udkfz
000181223 7001_ $$00000-0003-4837-3706$$aCharlet, Alexandre$$b5
000181223 7001_ $$0P:(DE-He78)b2142a2557ce071790760d0126e259d3$$aGrinevich, Valery$$b6
000181223 7001_ $$aNeumann, Inga D$$b7
000181223 773__ $$0PERI:(DE-600)1475274-8$$a10.1523/JNEUROSCI.2161-17.2017$$gVol. 37, no. 50, p. 12214 - 12225$$n50$$p12214 - 12225$$tThe journal of neuroscience$$v37$$x0270-6474$$y2017
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