2014
Memory Enhancement by Targeting Cdk5 Regulation of NR2B
Plattner F, Hernández A, Kistler TM, Pozo K, Zhong P, Yuen EY, Tan C, Hawasli AH, Cooke SF, Nishi A, Guo A, Wiederhold T, Yan Z, Bibb JA. Memory Enhancement by Targeting Cdk5 Regulation of NR2B. Neuron 2014, 81: 1070-1083. PMID: 24607229, PMCID: PMC4010123, DOI: 10.1016/j.neuron.2014.01.022.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCells, CulturedCyclin-Dependent Kinase 5FemaleHippocampusMaleMemoryMemory DisordersMiceMice, Inbred C57BLMice, KnockoutMolecular Sequence DataNeuronal PlasticityNeuronsOrgan Culture TechniquesPhosphorylationRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateSynaptic TransmissionConceptsCell surface expressionReceptor cell surface expressionCyclin-dependent kinase 5Cdk5 regulationN-methyl-D-aspartate receptorsRegulatory mechanismsKinase 5NR2B functionSurface expressionNMDAR functionSubunit NR2BSynaptic plasticityEnhancerFundamental roleRegulationMemory formationNMDAR subunit NR2BCognitive enhancersValid treatment strategyPrime targetSynaptic transmissionNR2B phosphorylationNR2BPhosphorylationSurface level
2013
Restoration of Glutamatergic Transmission by Dopamine D4 Receptors in Stressed Animals*
Yuen EY, Zhong P, Li X, Wei J, Yan Z. Restoration of Glutamatergic Transmission by Dopamine D4 Receptors in Stressed Animals*. Journal Of Biological Chemistry 2013, 288: 26112-26120. PMID: 23884421, PMCID: PMC3764814, DOI: 10.1074/jbc.m112.396648.Peer-Reviewed Original ResearchConceptsD4 receptorsDopamine D4 receptorExcitatory transmissionGlutamatergic transmissionPrefrontal cortexAMPA receptor-mediated synaptic transmissionReceptor-mediated synaptic transmissionCalcium/calmodulin kinase II activityEffects of D4PFC pyramidal neuronsCalmodulin kinase II activityKey brain regionsAttention deficit hyperactivity disorderBi-directional regulationDeficit hyperactivity disorderPyramidal neuronsCortical excitabilityDopaminergic inputSynaptic actionsSynaptic transmissionPotent reductionAMPA receptorsKinase II activityStressed animalsMaladaptive changesEstrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and cognition
Wei J, Yuen EY, Liu W, Li X, Zhong P, Karatsoreos IN, McEwen BS, Yan Z. Estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and cognition. Molecular Psychiatry 2013, 19: 588-598. PMID: 23835908, DOI: 10.1038/mp.2013.83.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAromataseAromatase InhibitorsCognitionEstradiolEstrogensFemaleGlutamic AcidMaleMemory DisordersPrefrontal CortexPyramidal CellsRats, Sprague-DawleyReceptors, EstrogenReceptors, GlutamateRecognition, PsychologyRNA, MessengerSex CharacteristicsStress, PsychologicalSynaptic TransmissionConceptsTemporal order recognition memoryGlutamatergic transmissionPrefrontal cortexStressed malesPFC of femalesNormal glutamatergic transmissionGlutamate receptor surface expressionPFC pyramidal neuronsYoung female ratsAdministration of estradiolLevels of aromatasePFC-dependent cognitionReceptor surface expressionBiosynthesis of estrogensEstrogen protectsPyramidal neuronsGlutamatergic deficitsRestraint stressFemale ratsEstrogen receptorGlutamate receptorsDetrimental effectsDimorphic effectsMemory impairmentStressed females
2012
Repeated Stress Causes Cognitive Impairment by Suppressing Glutamate Receptor Expression and Function in Prefrontal Cortex
Yuen EY, Wei J, Liu W, Zhong P, Li X, Yan Z. Repeated Stress Causes Cognitive Impairment by Suppressing Glutamate Receptor Expression and Function in Prefrontal Cortex. Neuron 2012, 73: 962-977. PMID: 22405206, PMCID: PMC3302010, DOI: 10.1016/j.neuron.2011.12.033.Peer-Reviewed Original ResearchMeSH Keywords2-Amino-5-phosphonovalerate6-Cyano-7-nitroquinoxaline-2,3-dioneAnalysis of VarianceAnimalsBicucullineCognition DisordersDisease Models, AnimalEndosomal Sorting Complexes Required for TransportExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsF-Box ProteinsGABA-A Receptor AntagonistsImmunoprecipitationIn Vitro TechniquesMaleNedd4 Ubiquitin Protein LigasesNeuropsychological TestsPrefrontal CortexPyramidal CellsRatsRats, Sprague-DawleyReceptors, GlutamateRecognition, PsychologyRestraint, PhysicalRNA, Small InterferingStress, PsychologicalUbiquitin-Protein LigasesConceptsGlutamate receptor expressionPrefrontal cortexRepeated stressReceptor expressionRecognition memoryCognitive processesTemporal order recognition memoryPFC pyramidal neuronsStress-related mental disordersJuvenile male ratsGlutamatergic responsesGlutamatergic transmissionPyramidal neuronsMale ratsSynaptic transmissionStressed animalsInhibition of proteasomeMaladaptive changesGlucocorticoid receptorCognitive impairmentNR1 subunitMental disordersChronic stressUbiquitin/proteasome-mediated degradationReceptor turnover
2011
Cellular Mechanisms for Dopamine D4 Receptor-induced Homeostatic Regulation of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors*
Yuen EY, Yan Z. Cellular Mechanisms for Dopamine D4 Receptor-induced Homeostatic Regulation of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors*. Journal Of Biological Chemistry 2011, 286: 24957-24965. PMID: 21622557, PMCID: PMC3137069, DOI: 10.1074/jbc.m111.221416.Peer-Reviewed Original ResearchConceptsGlutamatergic transmissionPFC neuronsPrefrontal cortexCalcium/calmodulin kinase II activityAMPAR responsesIsoxazolepropionic acid (AMPA) receptorsHomeostatic regulationCalmodulin kinase II activityAttention deficit hyperactivity disorderBi-directional regulationDopamine D4 receptorDeficit hyperactivity disorderAberrant dopaminePyramidal neuronsAMPA receptorsKinase II activitySynaptic currentsSynaptic targetingMental illnessAcid receptorsReceptor functionD4 receptorsCaMKII inhibitionActivity stateDistinct signaling mechanisms
2010
Homeostatic regulation of glutamatergic transmission by dopamine D4 receptors
Yuen EY, Zhong P, Yan Z. Homeostatic regulation of glutamatergic transmission by dopamine D4 receptors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 22308-22313. PMID: 21135234, PMCID: PMC3009820, DOI: 10.1073/pnas.1010025108.Peer-Reviewed Original ResearchConceptsSynaptic transmissionPrefrontal cortex pyramidal neuronsCortex pyramidal neuronsExcitatory synaptic transmissionAttention deficit hyperactivity disorderRole of dopamineDopamine D4 receptorGlutamatergic transmissionPyramidal neuronsCortical excitabilityProfound depressionMental disordersSynaptic functionBrain regionsD4 receptorsSynaptic factorsAMPAR traffickingPrefrontal cortexDistinct signaling pathwaysHyperactivity disorderCaMKII activityBidirectional regulationHomeostatic regulationReceptorsSignaling pathwaysMechanisms for acute stress-induced enhancement of glutamatergic transmission and working memory
Yuen EY, Liu W, Karatsoreos IN, Ren Y, Feng J, McEwen BS, Yan Z. Mechanisms for acute stress-induced enhancement of glutamatergic transmission and working memory. Molecular Psychiatry 2010, 16: 156-170. PMID: 20458323, PMCID: PMC3108461, DOI: 10.1038/mp.2010.50.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBiophysicsCells, CulturedCorticosteroneDose-Response Relationship, DrugDrug InteractionsElectric StimulationExcitatory Amino Acid AgentsExcitatory Postsynaptic PotentialsGene Expression RegulationGlutamic AcidGreen Fluorescent ProteinsHormone AntagonistsImmediate-Early ProteinsIn Vitro TechniquesLong-Term PotentiationMaleMaze LearningMemory, Short-TermMifepristonePatch-Clamp TechniquesPeptidesPrefrontal CortexProtein Serine-Threonine KinasesPyramidal CellsRab GTP-Binding ProteinsRatsRats, Sprague-DawleyReceptors, GlutamateRNA, Small InterferingStress, PsychologicalSynaptic TransmissionTime FactorsTransfectionConceptsPrefrontal cortexGlutamatergic transmissionAcid receptorsPFC pyramidal neuronsAspartic acid (NMDA) receptorsIsoxazolepropionic acid (AMPA) receptorsInduction of serumCorticosteroid stress hormonesFunction of NMDARsStress-induced enhancementSustained potentiationPyramidal neuronsCorticosterone treatmentSynaptic responsesSynaptic transmissionBehavioral stressorsGlucocorticoid-inducible kinaseGlucocorticoid receptorAcute stressStress hormonesΑ-aminoSurface expressionReceptorsUnderlying mechanismReceptor recyclingDelivery of GABAARs to Synapses Is Mediated by HAP1-KIF5 and Disrupted by Mutant Huntingtin
Twelvetrees A, Yuen E, Arancibia-Carcamo I, MacAskill A, Rostaing P, Lumb M, Humbert S, Triller A, Saudou F, Yan Z, Kittler J. Delivery of GABAARs to Synapses Is Mediated by HAP1-KIF5 and Disrupted by Mutant Huntingtin. Neuron 2010, 65: 53-65. PMID: 20152113, PMCID: PMC2841506, DOI: 10.1016/j.neuron.2009.12.007.Peer-Reviewed Original ResearchConceptsHuntingtin-associated protein 1Huntington's diseaseInhibitory postsynaptic currentsMutant huntingtinInhibitory synaptic currentsBrain excitabilityPostsynaptic currentsSynaptic inhibitionTherapeutic approachesSynaptic currentsDiseaseBrain information processingMolecular targetsSynapsesProtein 1Protein 5Protein huntingtinHuntingtinReceptorsPolyglutamine repeatsInhibitionGABAARsExcitability
2009
Assembly of a β2‐adrenergic receptor—GluR1 signalling complex for localized cAMP signalling
Joiner M, Lisé M, Yuen E, Kam A, Zhang M, Hall D, Malik Z, Qian H, Chen Y, Ulrich J, Burette A, Weinberg R, Law P, El‐Husseini A, Yan Z, Hell J. Assembly of a β2‐adrenergic receptor—GluR1 signalling complex for localized cAMP signalling. The EMBO Journal 2009, 29: 482-495. PMID: 19942860, PMCID: PMC2824466, DOI: 10.1038/emboj.2009.344.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl CyclasesAnimalsCalcium ChannelsCells, CulturedCerebral CortexCyclic AMP-Dependent Protein KinasesDisks Large Homolog 4 ProteinElectrophysiologyGene Expression RegulationGTP-Binding Protein alpha Subunits, GsHippocampusIntracellular Signaling Peptides and ProteinsMembrane ProteinsNeuronsRatsRats, Sprague-DawleyReceptors, Adrenergic, beta-2Receptors, AMPAConceptsUnknown molecular mechanismsMajor target proteinGluR1 surface expressionLocalized cAMPTarget proteinsMolecular mechanismsPhosphorylation of GluR1Selective regulationAdenylyl cyclaseProteinPSD-95PhosphorylationSurface expressionGlutamate receptor subunits GluR1PKAAssemblyPostsynaptic sitesCentral noradrenergic signalingHomologuesSubunit GluR1ComplexesCAMPSignalingAdrenergic receptorsStargazinAcute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory
Yuen EY, Liu W, Karatsoreos IN, Feng J, McEwen BS, Yan Z. Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 14075-14079. PMID: 19666502, PMCID: PMC2729022, DOI: 10.1073/pnas.0906791106.Peer-Reviewed Original ResearchConceptsAcute stressPrefrontal cortexGlucocorticoid receptorPotentiation of NMDARPFC pyramidal neuronsLong-term potentiationKey brain regionsCorticosteroid stress hormonesGR-dependent mechanismGlutamatergic transmissionPyramidal neuronsSynaptic transmissionBehavioral stressorsSynaptic currentsPFC neuronsBehavioral testsBrain regionsChronic stressAMPAR subunitsRecurrent excitationStress hormonesBeneficial effectsCellular mechanismsSurface expressionNMDAR
2008
Modulation of Neuronal Excitability by Serotonin-NMDA Interactions in Prefrontal Cortex
Zhong P, Yuen E, Yan Z. Modulation of Neuronal Excitability by Serotonin-NMDA Interactions in Prefrontal Cortex. Molecular And Cellular Neuroscience 2008, 38: 290-299. PMID: 18455431, PMCID: PMC2477738, DOI: 10.1016/j.mcn.2008.03.003.Peer-Reviewed Original ResearchMeSH Keywords8-Hydroxy-2-(di-n-propylamino)tetralinAction PotentialsAnimalsExcitatory Amino Acid AgonistsExtracellular Signal-Regulated MAP KinasesMAP Kinase Signaling SystemN-MethylaspartateOrgan Culture TechniquesPrefrontal CortexPyramidal CellsRatsRats, Sprague-DawleyReceptor, Serotonin, 5-HT1AReceptor, Serotonin, 5-HT2AReceptors, N-Methyl-D-AspartateSerotoninSerotonin Receptor AgonistsStress, PhysiologicalSwimmingConceptsExtracellular signal-regulated kinaseProtein kinase AProtein kinase CActivation of ERKSignal-regulated kinaseNeuronal excitabilityKinase AMolecule downstreamERK activationPrefrontal cortexKinase CNMDA receptorsStressful conditionsMental disordersBiochemical evidencePFC neuronal firingPFC pyramidal neuronsPresence of NMDAAction potential firingNMDA-dependent mannerDPAT effectsAgonist alphaPyramidal neuronsReceptor subtypesActivation
2007
The Phosphorylation State of GluR1 Subunits Determines the Susceptibility of AMPA Receptors to Calpain Cleavage*
Yuen EY, Liu W, Yan Z. The Phosphorylation State of GluR1 Subunits Determines the Susceptibility of AMPA Receptors to Calpain Cleavage*. Journal Of Biological Chemistry 2007, 282: 16434-16440. PMID: 17428797, DOI: 10.1074/jbc.m701283200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein KinasesCalpainCells, CulturedCerebral CortexEnzyme ActivationNeuronsPhosphoprotein PhosphatasesPhosphorylationProtein Phosphatase 1Protein Processing, Post-TranslationalProtein SubunitsRatsRats, Sprague-DawleyReceptors, AMPATime FactorsConceptsCalpain cleavagePhosphorylation stateProteolytic cleavageDependent protein kinase IITerminal fusion proteinEffect of phosphorylationProtein phosphatase 1/2AProtein kinase IIPhosphorylation sitesProtein kinaseCalpain cleavage sitesGluR1 subunitKinase IIFusion proteinActive CaMKIIAMPAR currentsCalpain regulationCleavage siteIsoxazoleproprionic acid (AMPA) receptorSubunitsIonotropic glutamate receptorsN-methyl-D-aspartate receptorsPhysiological studiesExcitatory synaptic transmissionAMPA receptor currentsCalpain regulation of AMPA receptor channels in cortical pyramidal neurons
Yuen EY, Gu Z, Yan Z. Calpain regulation of AMPA receptor channels in cortical pyramidal neurons. The Journal Of Physiology 2007, 580: 241-254. PMID: 17234699, PMCID: PMC2075435, DOI: 10.1113/jphysiol.2006.122754.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCalpainCells, CulturedCerebral CortexElectrophysiologyEndocytosisGerbillinaeImmunohistochemistryMaleMAP Kinase Kinase 2NeuronsNeuroprotective AgentsPatch-Clamp TechniquesPyramidal CellsRatsRats, Sprague-DawleyReceptors, AMPAReceptors, Cell SurfaceReceptors, N-Methyl-D-AspartateStimulation, ChemicalSynapsesSynaptic TransmissionConceptsCortical pyramidal neuronsNMDA receptorsPyramidal neuronsAMPA receptorsNMDA treatmentCalpain inhibitorsIschaemia-induced depressionFast excitatory synaptic transmissionTransient ischemic insultAMPAR-mediated currentsExcitatory synaptic transmissionCalpain-dependent mannerAMPA receptor channelsSelective calpain inhibitorsExcitotoxic conditionsIschemic animalsIschemic insultNeuronal excitotoxicityAMPAR currentsAMPA responsesCortical culturesExtracellular glutamateGlutamate receptorsGlutamate triggersNeuronal excitability
2006
Adrenergic modulation of NMDA receptors in prefrontal cortex is differentially regulated by RGS proteins and spinophilin
Liu W, Yuen EY, Allen PB, Feng J, Greengard P, Yan Z. Adrenergic modulation of NMDA receptors in prefrontal cortex is differentially regulated by RGS proteins and spinophilin. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 18338-18343. PMID: 17101972, PMCID: PMC1838752, DOI: 10.1073/pnas.0604560103.Peer-Reviewed Original ResearchConceptsExcitatory postsynaptic currentsNMDA receptorsAlpha1-ARNMDAR currentsPrefrontal cortexNoradrenergic systemPFC neuronsAlpha2-AR agonistNMDAR EPSC amplitudePFC pyramidal neuronsPaired-pulse ratioAlpha2-adrenergic receptorsPhospholipase C-inositolEffect of RGS4Norepinephrine transporter inhibitorG protein-coupled receptorsSpinophilin knockout miceProtein-coupled receptorsAdrenergic modulationPyramidal neuronsPFC slicesPostsynaptic currentsMood controlMutant miceTransporter inhibitors