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 firingThe meso-connectomes of mouse, marmoset, and macaque: network organization and the emergence of higher cognition
Magrou L, Joyce M, Froudist-Walsh S, Datta D, Wang X, Martinez-Trujillo J, Arnsten A. The meso-connectomes of mouse, marmoset, and macaque: network organization and the emergence of higher cognition. Cerebral Cortex 2024, 34: bhae174. PMID: 38771244, PMCID: PMC11107384, DOI: 10.1093/cercor/bhae174.Peer-Reviewed Original ResearchConceptsInter-areal connectionsVisual cortexPrimary visual cortexHigher cortical areasMacaque cortexPrimate specializationHigher cognitionPrimate cortexV1Working memory storageDendritic spine densityTop-down regulationPrefrontal cortexConnection structureSpine densityFunctional segregationCortical areasFrontal areasCortexConnectomeNetwork organizationMemory storageMultimodal associationβ1-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 spinesThe 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
Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in “Long-COVID19”
Fesharaki-Zadeh A, Lowe N, Arnsten A. Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in “Long-COVID19”. Neuroimmunology Reports 2023, 3: 100154. DOI: 10.1016/j.nerep.2022.100154.Peer-Reviewed Original ResearchN-acetylcysteineCognitive deficitsΑ2A-adrenoceptor agonistsPrefrontal cortexCOVID19 infectionPlacebo-controlled trialOpen-label treatmentCommon side effectsExecutive functionPFC connectionsBrain fogAcid blockadeLabel treatmentHypotensive episodesGuanfacine treatmentNMDA receptorsPatient brieflySide effectsClinical experienceGuanfacineCognitive impairmentPatientsPrefrontal connectivityDemonstrate efficacyPrefrontal function
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 ResearchSubcellular localization of PDE4D and HCN1 in rhesus macaque entorhinal cortex layer II: Signature of vulnerability in Alzheimer’s disease
Datta D, Mentone S, Morozov Y, van Dyck C, Arnsten A. Subcellular localization of PDE4D and HCN1 in rhesus macaque entorhinal cortex layer II: Signature of vulnerability in Alzheimer’s disease. Alzheimer's & Dementia 2022, 17 DOI: 10.1002/alz.054671.Peer-Reviewed Original ResearchEntorhinal cortex layer IICortex layer IILayers IIAlzheimer's diseaseTau pathologySmooth endoplasmic reticulumPostsynaptic compartmentsPrefrontal cortexLayer II cellsLayer II stellate cellsDisease courseAsymmetric synapsesGlutamatergic circuitsDendritic shaftsCalcium dysregulationGlutamatergic synapsesSpine apparatusExcitatory synapsesCalcium leakAD subjectsDendritic spinesStellate cellsAssociation cortexCalcium extrusionSynaptic strength
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 Research
2020
Insights into Cognitive Disorders in Aging and Mental Illness: Molecular Influences on Circuits of the Prefrontal Cortex
Arnsten A. Insights into Cognitive Disorders in Aging and Mental Illness: Molecular Influences on Circuits of the Prefrontal Cortex. 2020 DOI: 10.1093/oxfordhb/9780190069162.013.4.Peer-Reviewed Original ResearchPrefrontal cortexAbsence of sensory stimulationGoal-directed behaviorTop-down controlWorking memoryPrefrontal microcircuitsAffective disordersDynamic network connectivityMental disordersArousal systemCognitive disordersMental illnessCortical synaptic connectivityAbstract thoughtCortexRepresentation of informationDisordersSensory stimulationSynaptic strengthAlzheimer's diseaseRecurrent excitatory connectionsSynaptic connectionsExcitatory connectionsSchizophreniaNetwork connectivityMuscarinic 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 diseaseChapter 2 The Cellular Mechanisms of Executive Functions and Working Memory Relevance to Mental Disorders
Lightbourne T, Arnsten A. Chapter 2 The Cellular Mechanisms of Executive Functions and Working Memory Relevance to Mental Disorders. 2017, 21-40. DOI: 10.1016/b978-0-12-803676-1.00002-7.Peer-Reviewed Original ResearchPrefrontal cortexAttention deficit hyperactivity disorderDevastating neuropsychiatric disorderAdvanced ageTopographical organizationTherapeutic interventionsAlzheimer's diseaseMental disordersBrain regionsNeuropsychiatric pathologiesNormal individualsHigher-order cognitive abilitiesNeuropsychiatric disordersUncontrollable stressHyperactivity disorderCellular mechanisms
2015
Catecholamine mechanisms in the prefrontal cortex: proven strategies for enhancing higher cognitive function
Berridge C, Arnsten A. Catecholamine mechanisms in the prefrontal cortex: proven strategies for enhancing higher cognitive function. Current Opinion In Behavioral Sciences 2015, 4: 33-40. DOI: 10.1016/j.cobeha.2015.01.002.Peer-Reviewed Original ResearchAttention deficit hyperactivity disorderPharmacological treatmentCognitive dysfunctionPrefrontal cognitive dysfunctionCognition-enhancing effectsMultiple psychiatric disordersSpecific intracellular pathwaysDeficit hyperactivity disorderPrefrontal catecholaminesClinical efficacyCatecholamine mechanismsADHD medicationNovel medicationsReceptor mechanismsPrefrontal cognitionPsychiatric disordersCatecholamine receptorsCatecholamine modulationHigher cognitive functionsCognitive functionPrefrontal cortexHyperactivity disorderImproved treatmentIntracellular pathwaysKey modulatorDopamine’s Actions in Primate Prefrontal Cortex: Challenges for Treating Cognitive Disorders
Arnsten AF, Wang M, Paspalas CD. Dopamine’s Actions in Primate Prefrontal Cortex: Challenges for Treating Cognitive Disorders. Pharmacological Reviews 2015, 67: 681-696. PMID: 26106146, PMCID: PMC4485014, DOI: 10.1124/pr.115.010512.Peer-Reviewed Original ResearchConceptsCell firingPyramidal cell dendritesD2 receptor familyFrontal eye fieldPrimate prefrontal cortexGABA interneuronsCortical dopamineDopamine actionGlutamate releaseEndogenous dopamineDA cellsCell dendritesD1R agonistDendritic spinesCognitive disordersOrbital PFCEye fieldPositive symptomsLikely projectResponse cellsCognitive deficitsPrefrontal cortexStimulation speedFeedback neuronsD1R
2014
Guanfacine extended release for the treatment of attention-deficit/hyperactivity disorder in children and adolescents
Connor DF, Arnsten A, Pearson GS, Greco GF. Guanfacine extended release for the treatment of attention-deficit/hyperactivity disorder in children and adolescents. Expert Opinion On Pharmacotherapy 2014, 15: 1601-1610. PMID: 24992513, DOI: 10.1517/14656566.2014.930437.Peer-Reviewed Original ResearchConceptsAttention-deficit/hyperactivity disorderHyperactivity disorderSymptoms of ADHDEvidence-based treatmentsTraumatic stressBehavioral dysregulationADHD studiesSmall effect sizesPrefrontal cortexAdolescents 6Behavioral conditionsAdolescentsEffect sizeGXRPsycINFO databasesGuanfacinePsychostimulantsShire PharmaceuticalsOpen trialChildrenPotential promiseSecond-line treatmentDisordersAntihypertensive agentsAdrenoreceptor agonist