2024
Key Roles of CACNA1C/Cav1.2 and CALB1/Calbindin in Prefrontal Neurons Altered in Cognitive Disorders
Datta D, Yang S, Joyce M, Woo E, McCarroll S, Gonzalez-Burgos G, Perone I, Uchendu S, Ling E, Goldman M, Berretta S, Murray J, Morozov Y, Arellano J, Duque A, Rakic P, O’Dell R, van Dyck C, Lewis D, Wang M, Krienen F, Arnsten A. Key Roles of CACNA1C/Cav1.2 and CALB1/Calbindin in Prefrontal Neurons Altered in Cognitive Disorders. JAMA Psychiatry 2024, 81: 870-881. PMID: 38776078, PMCID: PMC11112502, DOI: 10.1001/jamapsychiatry.2024.1112.Peer-Reviewed Original ResearchDorsolateral prefrontal cortexPrefrontal cortexLayer III pyramidal cellsWorking memoryCognitive disordersNeuronal firingPrimate dorsolateral prefrontal cortexPyramidal cellsSpatial working memoryWorking memory performanceRisk of mental disordersCalcium-related proteinsReduced neuronal firingL-type calcium channel Cav1.2GluN2B-NMDA receptorsL-type calcium channel activityPrefrontal neuronsL-type calcium channel blockerMemory performanceL-type calcium channelsMental disordersRisk of cognitive disordersCognitive behaviorProtein expressionAssociated with increased riskStress and inflammation target dorsolateral prefrontal cortex function: Neural mechanisms underlying weakened cognitive control
Joyce M, Uchendu S, Arnsten A. Stress and inflammation target dorsolateral prefrontal cortex function: Neural mechanisms underlying weakened cognitive control. Biological Psychiatry 2024 PMID: 38944141, DOI: 10.1016/j.biopsych.2024.06.016.Peer-Reviewed Original ResearchMental disordersDorsolateral prefrontal cortex functionPrefrontal cortex functionSubgenual cingulate cortexRegulate emotional responsesDorsolateral prefrontal cortexChronic stress exposurePosterior association cortexMedial PFCCognitive controlPrefrontal cortexWorking memoryCingulate cortexRegulate attentionCortex functionNeural mechanismsDlPFCBrain regionsStress exposureAssociation cortexTop-down projectionsEmotional responsesSpine lossArousal statePersistent firingβ1-adrenoceptor expression on GABAergic interneurons in primate dorsolateral prefrontal cortex: potential role in stress-induced cognitive dysfunction
Joyce M, Yang S, Morin K, Duque A, Arellano J, Datta D, Wang M, Arnsten A. β1-adrenoceptor expression on GABAergic interneurons in primate dorsolateral prefrontal cortex: potential role in stress-induced cognitive dysfunction. Neurobiology Of Stress 2024, 30: 100628. PMID: 38550854, PMCID: PMC10973161, DOI: 10.1016/j.ynstr.2024.100628.Peer-Reviewed Original ResearchDorsolateral prefrontal cortexPrefrontal cortexStress-induced cognitive dysfunctionTreat stress-related disordersPrimate dorsolateral prefrontal cortexImpaired working memoryWorking memory deficitsWorking memory taskCalcium-binding proteins calbindinStress-related disordersClasses of inhibitory neuronsLevels of norepinephrineFast-spikingMemory taskDopamine releaseWorking memoryMemory deficitsInhibitory neuronsCognitive dysfunctionPV interneuronsGABAergic interneuronsDlPFCBehavior analysisCortexPyramidal cellsNanoscale imaging of pT217‐tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: Evidence of interneuronal trafficking and early‐stage neurodegeneration
Datta D, Perone I, Wijegunawardana D, Liang F, Morozov Y, Arellano J, Duque A, Xie Z, van Dyck C, Joyce M, Arnsten A. Nanoscale imaging of pT217‐tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: Evidence of interneuronal trafficking and early‐stage neurodegeneration. Alzheimer's & Dementia 2024, 20: 2843-2860. PMID: 38445818, PMCID: PMC11032534, DOI: 10.1002/alz.13737.Peer-Reviewed Original ResearchDynamic Network Connectivity: from monkeys to humans
Arnsten A, Wang M, D’Esposito M. Dynamic Network Connectivity: from monkeys to humans. Frontiers In Human Neuroscience 2024, 18: 1353043. PMID: 38384333, PMCID: PMC10879414, DOI: 10.3389/fnhum.2024.1353043.Peer-Reviewed Original ResearchDynamic network connectivityFunctional MRIFunctional connectivityHuman brain imaging researchDorsolateral prefrontal cortexNMDA receptor neurotransmissionBrain imaging researchHuman fMRI studiesPrefrontal cortexReceptor neurotransmissionWorking memoryFMRI studyBrain regionsPersistent neuronal firingNeuromodulator acetylcholineCognitive disordersCortical regionsDlPFCPost-synaptic densityArousal stateStrength of synaptic connectionsNeuronal firingCognitive statesImaging researchDendritic spinesInhibition of brain glutamate carboxypeptidase II (GCPII) to enhance cognitive function
Wiseman R, Bigos K, Arnsten A, Slusher B. Inhibition of brain glutamate carboxypeptidase II (GCPII) to enhance cognitive function. Advances In Pharmacology 2024 DOI: 10.1016/bs.apha.2024.10.018.Peer-Reviewed Original ResearchN-acetylaspartyl glutamateGlutamate carboxypeptidase IICognitive deficitsCognitive functionDorsolateral prefrontal cortex of primatesPrefrontal cortex of primatesHigher order cognitive processesDorsolateral prefrontal cortexMetabotropic glutamate receptor 3Inhibition of glutamate carboxypeptidase IIImprove cognitive deficitsEnhance cognitive functionImprove cognitive performanceEnzyme glutamate carboxypeptidase IIGlutamate receptor 3Executive functionCortex of primatesMGlu3 receptorsCarboxypeptidase IICognitive performanceCognitive processesPersistent neuronal firingClinical populationsNeuronal firingClinical workThe circuit mechanisms of working memory: Key roles of the dorsolateral prefrontal cortex
Arnsten A, Martinez-Trujillo J. The circuit mechanisms of working memory: Key roles of the dorsolateral prefrontal cortex. 2024 DOI: 10.1016/b978-0-443-15754-7.00038-9.Peer-Reviewed Original ResearchDorsolateral prefrontal cortexPrefrontal cortexWorking memoryMechanisms of working memorySpatial working memoryPosterior association cortexExecutive functionMediodorsal thalamusSketch padMental representationsAssociation cortexSubcortical connectionsCholinergic neurotransmissionCircuit mechanismsRecurrent excitatory circuitsNMDA receptorsAbstract thoughtPersistent firingPrimate researchCortexDlPFCExcitatory circuitsMemorySensory stimulationAlzheimer's disease
2023
Anatomical characterization of pT217‐tau in aged rhesus macaque association cortices: Relevance for trans‐synaptic propagation in sporadic Alzheimer’s Disease
Datta D, Mentone S, Morozov Y, van Dyck C, Arnsten A. Anatomical characterization of pT217‐tau in aged rhesus macaque association cortices: Relevance for trans‐synaptic propagation in sporadic Alzheimer’s Disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.075998.Peer-Reviewed Original ResearchTau pathologyEntorhinal cortexAlzheimer's diseaseRhesus macaquesBrain tau pathologyHigher brain circuitsHigher cortical circuitsPattern of neurodegenerationAged rhesus macaquesHuman Alzheimer's diseaseSporadic Alzheimer's diseaseTrans-synaptic propagationSoluble tau speciesSequence of tauDorsolateral prefrontal cortexAmyloid pathologyExtracellular spaceDendritic shaftsAdvanced neurodegenerationTau hyperphosphorylationInhibitory synapsesNeurofibrillary tanglesGlutamatergic synapsesSpine apparatusAD biomarkers
2022
P477. Anatomical Evaluation of Calcium-Related Schizophrenia Risk Genes in Rhesus Macaque Dorsolateral Prefrontal Cortex
Datta D, Mentone S, Morozov Y, Arnsten A. P477. Anatomical Evaluation of Calcium-Related Schizophrenia Risk Genes in Rhesus Macaque Dorsolateral Prefrontal Cortex. Biological Psychiatry 2022, 91: s281-s282. DOI: 10.1016/j.biopsych.2022.02.713.Peer-Reviewed Original ResearchMacaque dorsolateral prefrontal cortexDorsolateral prefrontal cortexSchizophrenia risk genesAnatomical evaluationPrefrontal cortexRisk genesCortex
2021
Subcellular Localization of Schizophrenia Risk Genes Encoding Cav1.2 (CACNA1C) and VIPR2 in Rhesus Macaque Dorsolateral Prefrontal Cortex
Datta D, Mentone S, Morozov Y, Arnsten A. Subcellular Localization of Schizophrenia Risk Genes Encoding Cav1.2 (CACNA1C) and VIPR2 in Rhesus Macaque Dorsolateral Prefrontal Cortex. Biological Psychiatry 2021, 89: s308. DOI: 10.1016/j.biopsych.2021.02.768.Peer-Reviewed Original ResearchMacaque dorsolateral prefrontal cortexDorsolateral prefrontal cortexSchizophrenia risk genesPrefrontal cortexRisk genes
2020
The calcium‐containing smooth endoplasmic reticulum is a focus of risk factors for early‐ and late‐onset Alzheimer’s disease
Datta D, Mentone S, Morozov Y, van Dyck C, Arnsten A. The calcium‐containing smooth endoplasmic reticulum is a focus of risk factors for early‐ and late‐onset Alzheimer’s disease. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.047651.Peer-Reviewed Original ResearchLate-onset Alzheimer's diseaseAlzheimer's diseaseSmooth endoplasmic reticulumAD pathologyCalcium dysregulationRisk factorsCalcium leakMonkey dorsolateral prefrontal cortexAutosomal dominant Alzheimer's diseaseNeurofibrillary tangle formationGenetic risk factorsMedial temporal lobeDorsolateral prefrontal cortexMonkey DLPFCAD neurodegenerationTangle formationAge-related pathologiesTemporal lobeAnimal modelsAssociation cortexPS2 mutationTherapeutic interventionsBrain regionsEtiological eventInternal calciumBiochemical characterization of age‐related calcium‐cAMP‐PKA signaling dysregulation and its effect on tau pathology in rhesus monkey cortex
Leslie S, Datta D, Wang M, van Dyck C, Arnsten A, Nairn A. Biochemical characterization of age‐related calcium‐cAMP‐PKA signaling dysregulation and its effect on tau pathology in rhesus monkey cortex. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.042017.Peer-Reviewed Original ResearchTau pathologyAge-related dysregulationAlzheimer's diseaseIntracellular calciumTau phosphorylationRhesus monkeysRat primary cortical culturesHuman post-mortem samplesVulnerable brain regionsSporadic Alzheimer's diseaseAmyloid-beta plaquesPrimary cortical culturesMain pathological hallmarksRhesus monkey cortexTau neurofibrillary tanglesYears of ageEarly-onset formAge-related vulnerabilityDorsolateral prefrontal cortexAge-related changesMonkey DLPFCPost-mortem samplesAD pathologyAmyloid pathologyUnknown etiologyMuscarinic M1 Receptors Modulate Working Memory Performance and Activity via KCNQ Potassium Channels in the Primate Prefrontal Cortex
Galvin VC, Yang ST, Paspalas CD, Yang Y, Jin LE, Datta D, Morozov YM, Lightbourne TC, Lowet AS, Rakic P, Arnsten AFT, Wang M. Muscarinic M1 Receptors Modulate Working Memory Performance and Activity via KCNQ Potassium Channels in the Primate Prefrontal Cortex. Neuron 2020, 106: 649-661.e4. PMID: 32197063, PMCID: PMC7244366, DOI: 10.1016/j.neuron.2020.02.030.Peer-Reviewed Original ResearchConceptsKCNQ channelsInverted-U dose responseCell firingPrefrontal cortexMuscarinic M1 receptorsKCNQ potassium channelsSingle-unit recordingsPrimate prefrontal cortexDorsolateral prefrontal cortexCholinergic alterationsKCNQ isoformsM1 receptorsPyramidal neuronsCholinergic depletionMuscarinic M1Cognitive disordersAged monkeysPersistent firingRecurrent excitationPotassium channelsAppropriate targetsDose responseM1R stimulationSensory inputCortex
2019
Noradrenergic α1-Adrenoceptor Actions in the Primate Dorsolateral Prefrontal Cortex
Datta D, Yang ST, Galvin VC, Solder J, Luo F, Morozov YM, Arellano J, Duque A, Rakic P, Arnsten A, Wang M. Noradrenergic α1-Adrenoceptor Actions in the Primate Dorsolateral Prefrontal Cortex. Journal Of Neuroscience 2019, 39: 2722-2734. PMID: 30755491, PMCID: PMC6445993, DOI: 10.1523/jneurosci.2472-18.2019.Peer-Reviewed Original ResearchConceptsΑ1-AR stimulationPosttraumatic stress disorderExcitatory effectsNeuronal firingDorsolateral prefrontal cortexBasal conditionsPrefrontal cortexΑ1-ARΑ1-adrenoceptorsInverted-U dose responseUncontrollable stressStress disorderTreatment of PTSDPrimate dorsolateral prefrontal cortexΑ1-AR expressionMajority of neuronsΑ1-AR agonistsPrefrontal cortical physiologyNoradrenergic releasePresynaptic excitationEndogenous NEPostsynaptic actionsExcitatory actionGlutamate releaseAxon terminals
2017
The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology
Paspalas CD, Carlyle BC, Leslie S, Preuss TM, Crimins JL, Huttner AJ, van Dyck C, Rosene DL, Nairn AC, Arnsten AFT. The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology. Alzheimer's & Dementia 2017, 14: 680-691. PMID: 29241829, PMCID: PMC6178089, DOI: 10.1016/j.jalz.2017.11.005.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseCortical pathologyEntorhinal cortexAnimal modelsBraak stage III/IVAlzheimer's diseaseStage III/IVRhesus macaquesProgression of tauAlzheimer-like pathologyPrimary visual cortexSequence of tauDorsolateral prefrontal cortexTau pathologyPreventive strategiesAssociation cortexVisual cortexPrefrontal cortexCortexPathologyDiseaseOld animalsProtein kinase A (PKA) phosphorylationGenetic insultsMacaquesmGluR2 versus mGluR3 Metabotropic Glutamate Receptors in Primate Dorsolateral Prefrontal Cortex: Postsynaptic mGluR3 Strengthen Working Memory Networks
Jin LE, Wang M, Galvin VC, Lightbourne TC, Conn PJ, Arnsten AF, Paspalas CD. mGluR2 versus mGluR3 Metabotropic Glutamate Receptors in Primate Dorsolateral Prefrontal Cortex: Postsynaptic mGluR3 Strengthen Working Memory Networks. Cerebral Cortex 2017, 28: 974-987. PMID: 28108498, PMCID: PMC5974790, DOI: 10.1093/cercor/bhx005.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsDose-Response Relationship, DrugExcitatory Amino Acid AgentsEye MovementsFemaleImage Processing, Computer-AssistedMacaca mulattaMagnetic Resonance ImagingMaleMemory, Short-TermNeuronsPost-Synaptic DensityPrefrontal CortexRatsReceptors, Metabotropic GlutamateSpatial LearningSubcellular FractionsConceptsPrimate dorsolateral prefrontal cortexMetabotropic glutamate receptorsDorsolateral prefrontal cortexGlutamate receptorsCell firingPrefrontal cortexMGluR2 positive allosteric modulatorsFocus of pathologyNovel therapeutic targetPositive allosteric modulatorsMGluR3 agonistGlutamate transmissionAstrocytic expressionGlial receptorsPostsynaptic componentsSpine synapsesInhibition of cAMPN-acetylaspartylglutamateMGluR3Therapeutic targetCognitive disordersLayer IIIMGluR2Postsynaptic cAMPAlzheimer's disease
2013
Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex
Yang Y, Paspalas CD, Jin LE, Picciotto MR, Arnsten AF, Wang M. Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 12078-12083. PMID: 23818597, PMCID: PMC3718126, DOI: 10.1073/pnas.1307849110.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAconitineAlpha7 Nicotinic Acetylcholine ReceptorAnalysis of VarianceAnimalsBridged Bicyclo Compounds, HeterocyclicCholinergic AgonistsCholinergic AntagonistsCognitionFemaleIontophoresisMacaca mulattaMaleMecamylamineMicroscopy, ImmunoelectronN-MethylaspartatePhenolsPiperidinesPrefrontal CortexQuinuclidinesReceptors, NicotinicSpatial BehaviorSynapsesVisual PerceptionConceptsDorsolateral prefrontal cortexΑ7 nAChRsPrefrontal cortexΑ7 nicotinic acetylcholine receptorGlutamatergic NMDA receptorsCognitive circuitsNicotinic α7 receptorsPrimary visual cortexNMDA receptor actionGenetic insultsNicotinic acetylcholine receptorsDlPFC circuitsPrimate dlPFCACh depletionNMDA actionNMDA receptorsPyramidal cellsΑ7 receptorsNeuronal firingNAChR blockadeAcetylcholine receptorsVisual cortexPersistent firingCognitive functionLow-dose stimulationNMDA Receptors Subserve Persistent Neuronal Firing during Working Memory in Dorsolateral Prefrontal Cortex
Wang M, Yang Y, Wang CJ, Gamo NJ, Jin LE, Mazer JA, Morrison JH, Wang XJ, Arnsten AF. NMDA Receptors Subserve Persistent Neuronal Firing during Working Memory in Dorsolateral Prefrontal Cortex. Neuron 2013, 77: 736-749. PMID: 23439125, PMCID: PMC3584418, DOI: 10.1016/j.neuron.2012.12.032.Peer-Reviewed Original ResearchConceptsPersistent firingDorsolateral prefrontal cortexAMPA receptorsPrefrontal cortexPrimate dorsolateral prefrontal cortexSystemic ketamine administrationPersistent neuronal firingAMPAR blockadePrimate dlPFCKetamine actionKetamine administrationNMDAR blockadeNMDA receptorsSystemic ketamineNetwork firingNeuronal firingAlzheimer's diseaseReceptor influencesImpair cognitionResponse cellsRecurrent excitationSensory stimulation
2010
The use of α-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder
Arnsten A. The use of α-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder. Expert Review Of Neurotherapeutics 2010, 10: 1595-1605. PMID: 20925474, PMCID: PMC3143019, DOI: 10.1586/ern.10.133.Peer-Reviewed Original ResearchConceptsAttention-deficit/hyperactivity disorderPrefrontal cortexHyperactivity disorderPFC functionPFC gray matterPFC pyramidal cellsPyramidal cell networksDorsolateral prefrontal cortexPFC connectionsReceptors inhibitsPyramidal cellsAdrenergic agonistsDendritic spinesVentromedial prefrontal cortexGray matterRelated disordersBrain regionsNeuropsychiatric disordersPotassium channelsDisordersPatientsRecent dataPhysiological connectionTreatmentExecutive functioning
2000
The Alpha-2A-Adrenoceptor Agonist, Guanfacine, Increases Regional Cerebral Blood Flow in Dorsolateral Prefrontal Cortex of Monkeys Performing a Spatial Working Memory Task
Avery R, Franowicz J, Studholme C, van Dyck C, Arnsten A. The Alpha-2A-Adrenoceptor Agonist, Guanfacine, Increases Regional Cerebral Blood Flow in Dorsolateral Prefrontal Cortex of Monkeys Performing a Spatial Working Memory Task. Neuropsychopharmacology 2000, 23: 240-249. PMID: 10942848, DOI: 10.1016/s0893-133x(00)00111-1.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-2 Receptor AgonistsAdrenergic alpha-AgonistsAnimalsCerebrovascular CirculationCognitionFemaleGuanfacineImage Processing, Computer-AssistedMacaca mulattaMagnetic Resonance ImagingMemoryPrefrontal CortexSpace PerceptionStimulation, ChemicalTomography, Emission-Computed, Single-PhotonConceptsRegional cerebral blood flowCerebral blood flowPrefrontal cortexDorsolateral prefrontal cortexBlood flowAlpha 2A-adrenoceptorsAuditory association areasSuperior temporal cortexBlood flow tracerSPECT measuresAdrenoceptor agonistsAdrenoceptor stimulationAlpha-2aMemory taskAdrenoreceptor agonistIntravenous cathetersGuanfacine treatmentTemporal cortexRCBF valuesAssociation areasBrain regionsGuanfacineCortexSpatial Working Memory taskCognitive performance