Astrocytic Modulation of Sleep Homeostasis and Cognitive睡眠平衡和認知的星形膠質(zhì)細胞調(diào)制課件

“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:dnSNARENosignificantalterationstoAstrocyticModulationofSleepHomeostasisandCognitive睡眠平衡和認知的星形膠質(zhì)細胞調(diào)制課件DuringtheLightPhase…(C-G,After6-HourSleepDeprivationProtocol)DuringtheLightPhase…(C-G,AMechanismassumedtobeinhibitionofextracellularadenosinebuild-up,actingviaA1RTests:Occlusion:(G)Mimic:(H)and(I)AstrocyticModulationofSleepHomeostasisandCognitive睡眠平衡和認知的星形膠質(zhì)細胞調(diào)制課件EffectsofSleepDeprivationonMemorySleepdeprivation,linkedtoimpairedmemoryandcognitivefunctionNovelObjectRecognitiontasksensitivetotheeffectsof“sleeppressure”EffectsofSleepDeprivationodnSNARE/A1RantagonismprotectsagainstSleepdeprivationinducedimpairmentsdnSNARERatsNodifferenceinexplorationtimeNodifferencesinAnxietyNoMotorimpairmentNocontextualfearconditioningimpairmentsNotanEffectofSleep,ratherSleepPressure/AdenosineAstrocyticModulationofSleepHomeostasisandCognitive睡眠平衡和認知的星形膠質(zhì)細胞調(diào)制課件“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:dnSNARENosignificantalterationstoAstrocyticModulationofSleepHomeostasisandCognitive睡眠平衡和認知的星形膠質(zhì)細胞調(diào)制課件DuringtheLightPhase…(C-G,After6-HourSleepDeprivationProtocol)DuringtheLightPhase…(C-G,AMechanismassumedtobeinhibitionofextracellularadenosinebuild-up,actingviaA1RTests:Occlusion:(G)Mimic:(H)