简介：Membranedepolarizationinducesthereleaseoftheserineproteinasetissue-typeplasminogenactivator(tPA)fromthepresynapticterminalofcerebralcorticalneurons.OnceinthesynapticcleftthistPApromotestheexocytosisandsubsequentendocyticretrievalofglutamate-containingsynapticvesicles,andregulatesthepostsynapticresponsetothepresynapticreleaseofglutamate.Indeed,tPAhasabidirectionaleffectonthecompositionofthepostsynapticdensity(PSD)thatdoesnotrequireplasmingenerationorthepresynapticreleaseofglutamate,butvariesaccordingtothebaselinelevelofneuronalactivity.Hence,ininactiveneuronstPAinducesphosphorylationandaccumulationinthePSDoftheCa~(2+)/calmodulin-dependentproteinkinaseIIα(pCaMKIIα),followedbypCaMKIIα-inducedphosphorylationandsynapticrecruitmentofGluR1-containingα-amino-3-hydroxy-5-methyl-4-isoxazolepropionicacid(AMPA)receptors.Incontrast,inactiveneuronswithincreasedlevelsofpCaMKIIαinthePSDtPAinducespCaMKIIαandpGluR1dephosphorylationandtheirsubsequentremovalfromthePSD.TheseeffectsrequireactivesynapticN-methyl-D-aspartate(NMDA)receptorsandcyclin-dependentkinase5(Cdk5)-inducedphosphorylationoftheproteinphosphatase1(PP1)atT320.ThesedataindicatethattPAisahomeostaticregulatorofthepostsynapticresponseofcerebralcorticalneuronstothepresynapticreleaseofglutamateviabidirectionalregulationofthepCaMKIIα/PP1switchinthePSD.

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