Differential Stress-Induced Neuronal Activation Patterns in Mouse Lines Selectively Bred for High, Normal or Low Anxiety 英文参考文献.docVIP

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Differential Stress-Induced Neuronal Activation Patterns in Mouse Lines Selectively Bred for High, Normal or Low Anxiety 英文参考文献.doc

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Differential Stress-Induced Neuronal Activation Patterns in Mouse Lines Selectively Bred for High, Normal or Low Anxiety 英文参考文献

DifferentialStress-InducedNeuronalActivationPatterns inMouseLinesSelectivelyBredforHigh,NormalorLow Anxiety PatrikMuigg1,SandraScheiber1,PeterSalchner1,MirjamBunck2,RainerLandgraf2,NicolasSingewald1* 1Department of Pharmacology and Toxicology, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innsbruck, Austria, 2MaxPlanckInstituteofPsychiatry,DepartmentBehavioralNeuroendocrinology,Munich,Germany Abstract Thereisevidenceforadisturbedperceptionandprocessingofemotionalinformationinpathologicalanxiety.Usingarat modeloftraitanxietygeneratedbyselectivebreeding,wepreviouslyrevealeddifferencesinchallenge-inducedneuronal activationinfear/anxiety-relatedbrainareasbetweenhigh(HAB)andlow(LAB)anxietyrats.Toconfirmwhetherfindings generalize to other species, we used the corresponding HAB/LAB mouse model and investigated c-Fos responses to elevatedopenarmexposure.Moreover,forthefirsttimeweincludednormalanxietymice(NAB)forcomparison.Theresults confirm that HAB mice show hyperanxious behavior compared to their LAB counterparts, with NAB mice displaying an intermediate anxiety phenotype. Open arm challenge revealed altered c-Fos response in prefrontal-cortical, limbic and hypothalamicareasinHABmiceascomparedtoLABmice,andthiswassimilartothedifferencesobservedpreviouslyinthe HAB/LAB rat lines.Inmice, however, additional differential c-Fos responsewas observedin subregions of theamygdala, hypothalamus,nucleusaccumbens,midbrainandpons.MostofthesedifferenceswerealsoseenbetweenHABandNAB mice,indicatingthatitispredominatelytheHABlineshowingalteredneuronalprocessing.Hypothalamichypoactivation detectedinLABversusNABmicemaybeassociatedwiththeirlow-anxiety/high-novelty-seekingphenotype.Thedetection ofsimilarlydisturbedactivationpatternsinakeysetofanxiety-relatedbrainareasintwoindependentmodelsreflecting psychopathological states of trait anxiety confirms the notion that the altered brain activation in HAB animals is indeed characteristicofenha