2025
472. Role of Voltage-Gated Calcium Channels in Vulnerable Pyramidal Neurons in Primate Dorsolateral Prefrontal Cortex: Elucidating the Role of Cav3.1 and Cav1.2 in Higher-Order Cognition
Datta D, Yang S, Gonzalez-Burgos G, Enwright J, Arion D, Lewis D, Wang M, Arnsten A. 472. Role of Voltage-Gated Calcium Channels in Vulnerable Pyramidal Neurons in Primate Dorsolateral Prefrontal Cortex: Elucidating the Role of Cav3.1 and Cav1.2 in Higher-Order Cognition. Biological Psychiatry 2025, 97: s291-s292. DOI: 10.1016/j.biopsych.2025.02.710.Peer-Reviewed Original ResearchDysregulated calcium signaling in the aged macaque entorhinal cortex associated with tau hyperphosphorylation
Bathla S, Datta D, Bolat D, Woo E, Duque A, Arellano J, Arnsten A, Nairn A. Dysregulated calcium signaling in the aged macaque entorhinal cortex associated with tau hyperphosphorylation. Frontiers In Aging Neuroscience 2025, 17: 1549770. PMID: 40365352, PMCID: PMC12069431, DOI: 10.3389/fnagi.2025.1549770.Peer-Reviewed Original ResearchTau pathologyTau hyperphosphorylationAlzheimer's diseaseAssociated with tau hyperphosphorylationSoluble phosphorylated tauSporadic Alzheimer's diseaseCalcium signalingDysregulated calcium signalingTau etiologyEarly stages of ADHyperphosphorylationSignaling pathwayHuman ADInflammatory signaling pathwaysCalpain-2Stages of ADMolecular processesHydrolyze cAMPTauEntorhinal cortexCarboxypeptidase IIGlutamate carboxypeptidase IIDephosphorylation39 Nanoscale 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. 39 Nanoscale imaging of pT217-tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: Evidence of interneuronal trafficking and early-stage neurodegeneration. Journal Of Clinical And Translational Science 2025, 9: 13-13. PMCID: PMC12038495, DOI: 10.1017/cts.2024.726.Peer-Reviewed Original ResearchDorsolateral prefrontal cortexPrefrontal cortexEntorhinal cortexStatistically significant age-related increaseTau pathologySignificant age-related increaseAlzheimer's diseaseAge-related increaseBrain circuitsRhesus macaquesAged rhesus macaquesAging brainAged macaquesCortical pathologyCortexAge spanDendritic spinesEarly-stage neurodegenerationBrainTau speciesSubcellular localizationInhibitory synapsesPhosphorylated proteinsDysmorphic mitochondriaPostsynaptic compartmentsContrasting patterns of extrasynaptic NMDAR-GluN2B expression in macaque subgenual cingulate and dorsolateral prefrontal cortices
Joyce M, Datta D, Arellano J, Duque A, Morozov Y, Morrison J, Arnsten A. Contrasting patterns of extrasynaptic NMDAR-GluN2B expression in macaque subgenual cingulate and dorsolateral prefrontal cortices. Frontiers In Neuroanatomy 2025, 19: 1553056. PMID: 40255911, PMCID: PMC12006084, DOI: 10.3389/fnana.2025.1553056.Peer-Reviewed Original ResearchSubgenual cingulate cortexDorsolateral prefrontal cortexPrefrontal cortexPutative pyramidal neuronsN-methyl-D-aspartate receptorsN-methyl-D-aspartateSporadic Alzheimer's diseaseSubgenual cingulateCingulate cortexWorking memoryMacaque dlPFCDlPFCNMDAR antagonistsGluN2B subunitVulnerable to alterationsCortexSynaptic expressionPyramidal neuronsSynaptic functionAlzheimer's diseaseNeurodegenerative processesExtrasynaptic sitesTau pathologySchizophreniaCingulateThe neuropathologic basis for translational biomarker development in the macaque model of late-onset Alzheimer's disease
Zeiss C, Huttner A, Nairn A, Arnsten A, Datta D, Strittmatter S, Vander Wyk B, Duque A. The neuropathologic basis for translational biomarker development in the macaque model of late-onset Alzheimer's disease. Journal Of Alzheimer’s Disease 2025, 104: 1243-1258. PMID: 40095666, DOI: 10.1177/13872877251323787.Peer-Reviewed Original ResearchAlzheimer's diseaseLate-onset Alzheimer's diseaseModel of late-onset Alzheimer's diseaseBraak stages III-IVDisruption of synaptic connectivityFormalin fixed paraffinAccumulation of senescence markersTau phosphorylationAmyloid-bFibrillar tauSenescence markersCo-morbiditiesPTau expressionLabile proteinBiomarker developmentStage III-IVSynaptic disruptionGlial fibrillary acidic proteinSenescence markers p16Fibrillary acidic proteinPredictive biomarkersFFPE tissuesMacaque modelAcidic proteinIII-IVSUSCEPTIBLE PYRAMIDAL NEURONS IN PRIMATE DORSOLATERAL PREFRONTAL CORTEX EXPRESS AN ENRICHED CALCIUM INTERACTOME: CRITICAL ROLE OF CALBINDIN AND CAV1.2 IN HIGHER-ORDER COGNITION
Datta *, Yang S, Joyce M, Woo E, McCarroll S, Gonzalez-Burgos G, Perone I, Uchendu S, Ling E, Goldman R, 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. SUSCEPTIBLE PYRAMIDAL NEURONS IN PRIMATE DORSOLATERAL PREFRONTAL CORTEX EXPRESS AN ENRICHED CALCIUM INTERACTOME: CRITICAL ROLE OF CALBINDIN AND CAV1.2 IN HIGHER-ORDER COGNITION. The International Journal Of Neuropsychopharmacology 2025, 28: i57-i58. PMCID: PMC11814899, DOI: 10.1093/ijnp/pyae059.100.Peer-Reviewed Original ResearchDorsolateral prefrontal cortexMacaque dlPFCPrefrontal cortexWorking memoryLayer 3 pyramidal cellsAlzheimer s diseasePrefrontal cortex dysfunctionExpression of Grin2bPyramidal cellsHigher-order cognitionIncreased risk of mental disordersRisk of neuropsychiatric disordersDendritic spine pathologyRisk of mental disordersIncreased risk of neuropsychiatric disordersL-type calcium channel Cav1.2Primate dlPFCDLPFC functionCognitive deficitsLayer III pyramidal cellsMemory impairmentPsychiatric disordersBrain circuitryNeuropsychiatric disordersMental representationsThe etiology and prevention of early‐stage tau pathology in higher cortical circuits: Insights from aging rhesus macaques
Datta D, Arnsten A. The etiology and prevention of early‐stage tau pathology in higher cortical circuits: Insights from aging rhesus macaques. Alzheimer's & Dementia 2025, 21: e14477. PMID: 39776253, PMCID: PMC11848412, DOI: 10.1002/alz.14477.Peer-Reviewed Original ResearchConceptsAged macaquesAged rhesus macaquesP-tauTau hyperphosphorylationCortical circuitsAmyloid-beta generationSoluble phosphorylated tauCognitive deficitsAged monkeysSoluble hyperphosphorylated tauSporadic Alzheimer's diseaseAssociation cortexEarly-stage pathologyRhesus macaquesIncreased ABCalcium dysregulationCalcium regulationToxic to neuronsHyperphosphorylated tauAmyloid-betaCortexInflammatory signalingP-tau217 levelsTau pathologyPhosphorylated tau
2024
Nanoscale imaging of pT217‐tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: Evidence of interneuronal trafficking and early‐stage neurodegeneration
Datta D. 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: e089418. PMCID: PMC11709465, DOI: 10.1002/alz.089418.Peer-Reviewed Original ResearchDorsolateral prefrontal cortexPrefrontal cortexEntorhinal cortexStatistically significant age-related increaseAged macaquesTau pathologySignificant age-related increaseAlzheimer's diseaseAge-related increaseCognitive deficitsBrain circuitsBrain expressionAging brainBrain pathologyCortical pathologyCortexEfficacy of novel treatmentsDlPFCAge spanDendritic spinesEarly-stage neurodegenerationInhibitory synapsesLayer IIBrainRhesus macaquesCharacterizing the Most Vulnerable Prefrontal Cortical Neurons in Schizophrenia
Arnsten A, Datta D. Characterizing the Most Vulnerable Prefrontal Cortical Neurons in Schizophrenia. American Journal Of Psychiatry 2024, 181: 861-864. PMID: 39350618, PMCID: PMC11714303, DOI: 10.1176/appi.ajp.20240731.Peer-Reviewed Original ResearchTranslating Prefrontal Cortex Insights to the Clinic and Society
Rowe J, Datta D, Fiebach C, Jaeggi S, Liston C, Luna B, Rasmussen S, Roberts A, Sinha R, Haber S. Translating Prefrontal Cortex Insights to the Clinic and Society. 2024, 319-360. DOI: 10.7551/mitpress/15679.003.0019.Peer-Reviewed Original ResearchKey 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 riskThe 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 associationAn overview of preclinical models of traumatic brain injury (TBI): relevance to pathophysiological mechanisms
Fesharaki-Zadeh A, Datta D. An overview of preclinical models of traumatic brain injury (TBI): relevance to pathophysiological mechanisms. Frontiers In Cellular Neuroscience 2024, 18: 1371213. PMID: 38682091, PMCID: PMC11045909, DOI: 10.3389/fncel.2024.1371213.Peer-Reviewed Original ResearchClosed-Head Impact Model of Engineered Rotational AccelerationModel of traumatic brain injuryPreclinical modelsPreclinical models of traumatic brain injuryAnimal modelsTraumatic brain injuryControlled cortical impact injuryRodent preclinical modelsDisease modifying effectFluid percussion injuryCortical impact injuryBlast injuryAnimal models of traumatic brain injuryBrain injuryMotor vehicle accidentsTherapeutic regimenPathophysiological mechanismsEtiology of traumatic brain injuryPharmacological agentsSports related injuriesInjury modelCalcium dysregulationPrevalence of traumatic brain injuryClinical treatmentClinical settingβ1-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 Research
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 biomarkersNanoscale imaging of pT217-tau in aged rhesus macaque: Trans-synaptic propagation and seeding of tau pathology in entorhinal cortex
Datta D, Arnsten A. Nanoscale imaging of pT217-tau in aged rhesus macaque: Trans-synaptic propagation and seeding of tau pathology in entorhinal cortex. Journal Of The Neurological Sciences 2023, 455: 122501. DOI: 10.1016/j.jns.2023.122501.Peer-Reviewed Original ResearchChronic GCPII (glutamate‐carboxypeptidase‐II) inhibition reduces pT217Tau levels in the entorhinal and dorsolateral prefrontal cortices of aged macaques
Bathla S, Datta D, Liang F, Barthelemy N, Wiseman R, Slusher B, Asher J, Zeiss C, Ekanayake‐Alper D, Holden D, Terwilliger G, Duque A, Arellano J, van Dyck C, Bateman R, Xie Z, Nairn A, Arnsten A. Chronic GCPII (glutamate‐carboxypeptidase‐II) inhibition reduces pT217Tau levels in the entorhinal and dorsolateral prefrontal cortices of aged macaques. Alzheimer's & Dementia: Translational Research & Clinical Interventions 2023, 9: e12431. PMID: 37915375, PMCID: PMC10617575, DOI: 10.1002/trc2.12431.Peer-Reviewed Original ResearchSporadic Alzheimer's diseaseEntorhinal cortexGCPII inhibitionDorsolateral prefrontal cortexChronic inhibitionTau pathologyTau hyperphosphorylationAged macaquesType 3 metabotropic glutamate receptorAlzheimer's diseasePrefrontal cortexRhesus macaquesVehicle-treated monkeysAged rhesus macaquesMetabotropic glutamate receptorsApparent side effectsAmyloid beta 1Regulation of calciumGCPII inhibitorsKey etiological factorGCPII activityPrimate dlPFCNeuronal damageCSF analysisCalcium dysregulationInteraction Between HCN and Slack Channels Regulates mPFC Pyramidal Cell Excitability in Working Memory Circuits
Wu J, El-Hassar L, Datta D, Thomas M, Zhang Y, Jenkins D, DeLuca N, Chatterjee M, Gribkoff V, Arnsten A, Kaczmarek L. Interaction Between HCN and Slack Channels Regulates mPFC Pyramidal Cell Excitability in Working Memory Circuits. Molecular Neurobiology 2023, 61: 2430-2445. PMID: 37889366, DOI: 10.1007/s12035-023-03719-8.Peer-Reviewed Original ResearchPFC pyramidal neuronsPyramidal cellsHCN channelsPrefrontal cortexPyramidal neuronsNeuronal firingSlack channelsPyramidal cell excitabilityRat prefrontal cortexPFC pyramidal cellsCell linesNon-selective cation channelsRecurrent excitatory connectionsCortical extractsNeuronal depolarizationNeuronal excitabilityPharmacological blockersSpecific blockerDendritic spinesKNa channelsCell excitabilityPostsynaptic spinesPersistent firingExcitatory connectionsNeural circuitsLocalization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer’s disease
Datta D, Perone I, Morozov Y, Arellano J, Duque A, Rakic P, van Dyck C, Arnsten A. Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer’s disease. Cerebral Cortex 2023, 33: 11501-11516. PMID: 37874022, PMCID: PMC10724870, DOI: 10.1093/cercor/bhad382.Peer-Reviewed Original ResearchConceptsHCN1 channelsTau pathologyGlutamate synapsesEntorhinal cortexCalcium actionInternal calcium releaseEntorhinal cortex stellate cellsDorsolateral prefrontal cortexSusceptible neuronsInitial pathologySelective vulnerabilityEtiological factorsTau phosphorylationStellate cellsAlzheimer's diseaseSpecific neuronsCalcium releasePrefrontal cortexCortexSynapse strengthPathologyCalcium signalingCalbindinDiseaseNeurons
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