Astrocytic Modulation of Sleep Homeostasis and Cognitive睡眠的平衡和认知的星形胶质细胞调制课件_第1页
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“AstrocyticModulationofSleepHomeostasisandCognitiveConsequencesofSleepLoss”MichaelM.Halassa,CedrickFlorian,TommasoFellin,JamesR.Munoz,So-YoungLee,TedAbel,PhilipG.Haydon,andMarcosG.FrankJournalClub,10-February-2009“AstrocyticModulationofSleeGliaGlia:Neurons=10:1Traditionally3typesofGliaAstrocytesOligodendrocytesMicrogliaRecentlyNG2+CellsAdded“BrainGlue”!?Functions©2009McGraw-HillCompanies,From“/newsletter/2006/2006Jul.html”GliaGlia:Neurons=10:1©2009MAstrocytes!DefinedByGFAP(GlialFibrillaryAcidicProtein)ExpressionHighlyRamified,IntracellularCouplingFunctions:MetabolicRolesK+

BufferingBloodBrainBarrierPrecursorCells?©2007TheUniversityofUtah,GeneticScienceLearningCenter

Astrocytes!DefinedByGFAP(GlOccupydefined,non-overlappingdomainsHippocampus>100,000SynapsesBushongetal.,2002Cortex2-8Somata300-600DendritesHalassaetal,2007BushongEA,MartoneME,JonesYZ,EllismanMHProtoplasmicastrocytesinCA1stratumradiatumoccupyseparateanatomicaldomains.JNeurosci22;183-92,2002BushongEA,MartoneME,JonesCopyright©2007SocietyforNeuroscienceHalassa,M.M.etal.J.Neurosci.2007;27:6473-6477Figure2.OneastrocyteenwrapsseveralneuronalsomataCopyright©2007SocietyforNeTheTripartiteSynapseFilipodiaandLamellipodiaEnvelopSynapseClearanceofNeurotransmittersReceptorsCalciumTransientsGliotransmissionTheTripartiteSynapseFilipodi…AndNowTHEPAPER…AndNowTHEPAPEROutlineGFAPDrivendnSNAREAttenuateexocytoticGliotransmissionAssessedeffectsonSleepandEEGPharmacologicalexperimentstocharacterisecauseoftheseeffectsObjectrecognitiontasktoexamineeffectsonsleepdeprivationinducedmemoryimpairmentsOutlineGFAPDrivendnSNAREdnSNARETetracyclineTransactivator(tTA)underGFAPpromoterdnSNAREundertet.OpromotertTAactivatestet.OanddrivesexpressionofdnSNAREConditionalsupression:Doxycyclineinthediet

<50%corticalastrocytesexpresstransgenednSNARETetracyclineTransactivNosignificantalterationstototalsleeptime,REMtime,NREMtime,or24-hourEEGspectrabetweengroupsOpenCircles/Bars:WildTypeClosedCircles/Bars:dnSNARENosignificantalterationsto“AstrocyticModulationofSleepHomeostasisandCognitive“睡眠的平衡和认知的星形胶质细胞调制课件DuringtheLightPhase…(C-G,After6-HourSleepDeprivationProtocol)DuringtheLightPhase…(C-G,AMechanismassumedtobeinhibitionofextracellularadenosinebuild-up,actingviaA1RTests:Occlusion:(G)Mimic:(H)and(I)“AstrocyticModulationofSleepHomeostasisandCognitive“睡眠的平衡和认知的星形胶质细胞调制课件EffectsofSleepDeprivationonMemorySleepdeprivation,linkedtoimpairedmemoryandcognitivefunctionNovelObjectRecognitiontasksensitivetotheeffectsof“sleeppressure”EffectsofSleepDeprivationodnSNARE/A1RantagonismprotectsagainstSleepdeprivationinducedimpairmentsdnSNARERatsNodifferenceinexplorationtimeNodifferencesinAnxietyNoMotorimpairmentNocontextualfea

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