资源描述：
《Neuronal basis of age-related working memory decline》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。
1、LETTERdoi:10.1038/nature10243Neuronalbasisofage-relatedworkingmemorydecline111111,211MinWang,NaoJ.Gamo,YangYang,LuE.Jin,Xiao-JingWang,MarkLaubach,JamesA.Mazer,DaeyeolLee1&AmyF.T.Arnsten6Manyofthecognitivedeficitsofnormalageing(forgetfulness,dis-periodinaworkingmem
2、orytask(Fig.1d).Thisabilitytomaintaintractibility,inflexibilityandimpairedexecutivefunctions)involveinformationthatisnolongerintheenvironmentisafundamental1–46prefrontalcortex(PFC)dysfunction.ThePFCguidesbehaviourprocessneededforabstractthoughtandflexiblerespondin
3、g.5andthoughtusingworkingmemory,whichareessentialfunctionsIntracellularsignallingpathwaysmodulatethephysiologicalstrength9intheinformationage.ManyPFCneuronsholdinformationinoftheserecurrent,excitatoryPFCnetworkconnections.Recentdataworkingmemorythroughexcitatoryne
4、tworksthatcanmaintainshowthatincreasedcAMPsignallingweakensnetworkconnectivityby6persistentneuronalfiringintheabsenceofexternalstimulation.openingpotassiumchannels,whereasinhibitingcAMPsignallingand/9Thisfragileprocessishighlydependentontheneurochemicalorclosingth
5、esechannelsstrengthensconnectivityandcognitiveability7environment.Forexample,elevatedcyclic-AMPsignallingreduces(Fig.1e).Specifically,cAMPsignallingseemstoweakenpersistentfiring8,9persistentfiringbyopeningHCNandKCNQpotassiumchannels.andimpairworkingmemorybyincreas
6、ingtheopenstateofHCNItisnotknownifmolecularchangesassociatedwithnormalageing(hyperpolarization-activatedcyclicnucleotide-gated)channelsthat8alterthephysiologicalpropertiesofPFCneuronsduringworkingarelocalizedonspineswherenetworksinterconnect.Recentdatamemory,asthe
7、rehavebeennoinvivorecordings,toourknowledge,indicatethatHCNchannelsmayalsogatesynapticinputsthroughfromPFCneuronsofagedmonkeys.HerewecharacterizethefirstinteractionswithKCNQchannels,whoseopenstateisincreasedby21recordingsofthiskind,revealingamarkedlossofPFCpersist
8、entcAMP-activatingproteinkinaseA(PKA).Studiesindicatethat22firingwithadvancingagethatcanberescuedbyrestoringanoptimalcAMPsignallingisdisinhibitedintheag
