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 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 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 Research
2023
Interrogating the Etiology of Sporadic Alzheimer’s Disease Using Aging Rhesus Macaques: Cellular, Molecular, and Cortical Circuitry Perspectives
Datta D. Interrogating the Etiology of Sporadic Alzheimer’s Disease Using Aging Rhesus Macaques: Cellular, Molecular, and Cortical Circuitry Perspectives. The Journals Of Gerontology Series A 2023, 78: 1523-1534. PMID: 37279946, PMCID: PMC10460555, DOI: 10.1093/gerona/glad134.Peer-Reviewed Original ResearchConceptsPrimate dorsolateral prefrontal cortexSporadic Alzheimer's diseaseAlzheimer's diseaseDorsolateral prefrontal cortexRhesus macaquesPrefrontal cortexSignificant risk factorsHuman Alzheimer's diseaseAspartic acid (NMDA) receptorsNonhuman primate modelNovel therapeutic strategiesCalcium-buffering proteinsPattern of pathologyInflammatory cascadeTau pathologyNeuropathological cascadeSynaptic dysfunctionRisk factorsPrimate modelNeurofibrillary tanglesAmyloid plaquesDendritic spinesTherapeutic strategiesGenetic predispositionAnimal models
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
Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates
Leslie SN, Kanyo J, Datta D, Wilson RS, Zeiss C, Duque A, Lam TT, Arnsten AFT, Nairn AC. Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates. Frontiers In Aging Neuroscience 2021, 13: 767322. PMID: 34867294, PMCID: PMC8637411, DOI: 10.3389/fnagi.2021.767322.Peer-Reviewed Original ResearchTau phosphorylationPrefrontal cortexAlzheimer's diseaseAge-related changesLayer III pyramidal cellsRhesus monkey prefrontal cortexSignificant risk factorsMonkey prefrontal cortexNon-human primatesAD pathologyTau levelsRisk factorsPyramidal cellsRodent modelsIdentifies ageRhesus monkeysLiquid chromatography-tandem mass spectrometryTherapeutic developmentNatural aging processSignificant increaseTauAgeDiseaseRobust labelingMonkeysStudies of aging nonhuman primates illuminate the etiology of early‐stage Alzheimer's‐like neuropathology: An evolutionary perspective
Arnsten AFT, Datta D, Preuss TM. Studies of aging nonhuman primates illuminate the etiology of early‐stage Alzheimer's‐like neuropathology: An evolutionary perspective. American Journal Of Primatology 2021, 83: e23254. PMID: 33960505, PMCID: PMC8550995, DOI: 10.1002/ajp.23254.Peer-Reviewed Original ResearchConceptsTau pathologyAssociation cortexAlzheimer's diseaseTau phosphorylationNMDAR-NR2BRhesus monkeysCognitive deficitsMonkey dorsolateral prefrontal cortexAlzheimer-like neuropathologyInternal calcium releaseGenetic mouse modelsDorsolateral prefrontal cortexSynaptic lossNeurofibrillary tanglesAmyloid plaquesMouse modelEarly molecular eventsSporadic formsAutosomal dominant formCalcium releasePerfusion fixationCortexPrefrontal cortexNonhuman primatesPathologySubcellular 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 ResearchChronic Stress Weakens Connectivity in the Prefrontal Cortex: Architectural and Molecular Changes
Woo E, Sansing LH, Arnsten AFT, Datta D. Chronic Stress Weakens Connectivity in the Prefrontal Cortex: Architectural and Molecular Changes. Chronic Stress 2021, 5: 24705470211029254. PMID: 34485797, PMCID: PMC8408896, DOI: 10.1177/24705470211029254.Peer-Reviewed Original ResearchLoss of spinesPrefrontal cortexSpine lossPersistent firingUncontrollable stressDendritic spine lossChronic stress exposureMarked cognitive impairmentInternal calcium releaseRecurrent excitatory connectionsCatecholamine releaseInflammatory signalingSynaptic connectivityCognitive disordersChronic exposureCalcium homeostasisPFC neuronsCognitive impairmentBrain regionsChronic stressCalcium releaseExcitatory connectionsStress exposurePotassium channelsSpine
2020
The genie in the bottle-magnified calcium signaling in dorsolateral prefrontal cortex
Arnsten AFT, Datta D, Wang M. The genie in the bottle-magnified calcium signaling in dorsolateral prefrontal cortex. Molecular Psychiatry 2020, 26: 3684-3700. PMID: 33319854, PMCID: PMC8203737, DOI: 10.1038/s41380-020-00973-3.Peer-Reviewed Original ResearchConceptsDorsolateral prefrontal cortexCognitive disordersPrefrontal cortexPrimate dorsolateral prefrontal cortexHigher cortical circuitsPrimary visual cortexInternal calcium releaseRisk of schizophreniaAge-related lossLevels of calciumDendritic atrophyAmyloid pathologyCalcium binding proteinInflammatory insultCalcium overloadTau phosphorylationCortical circuitsDendritic spinesNeuronal firingCalcium channelsAssociation cortexSynaptic efficacyVisual cortexAlzheimer's diseaseSpecial molecular mechanismMapping Phosphodiesterase 4D (PDE4D) in Macaque Dorsolateral Prefrontal Cortex: Postsynaptic Compartmentalization in Layer III Pyramidal Cell Circuits
Datta D, Enwright JF, Arion D, Paspalas CD, Morozov YM, Lewis DA, Arnsten AFT. Mapping Phosphodiesterase 4D (PDE4D) in Macaque Dorsolateral Prefrontal Cortex: Postsynaptic Compartmentalization in Layer III Pyramidal Cell Circuits. Frontiers In Neuroanatomy 2020, 14: 578483. PMID: 33328902, PMCID: PMC7714912, DOI: 10.3389/fnana.2020.578483.Peer-Reviewed Original ResearchDorsolateral prefrontal cortexSmooth endoplasmic reticulumPrefrontal cortexHuman dlPFCPrimate dorsolateral prefrontal cortexHuman post-mortem tissueInternal calcium releasePrimate association corticesPost-mortem tissueMacaque dorsolateral prefrontal cortexPrimate dlPFCAxospinous synapsesPV interneuronsGlutamatergic connectionsGlutamatergic synapsesPyramidal cellsAxon terminalsTransmitter releaseTau phosphorylationDendritic spinesPDE4 isozymesAssociation cortexLayer IIICAMP actionPostsynaptic labelingLaminar Differences in the Targeting of Dendritic Spines by Cortical Pyramidal Neurons and Interneurons in Human Dorsolateral Prefrontal Cortex
Glausier J, Datta D, Fish K, Chung D, Melchitzky D, Lewis D. Laminar Differences in the Targeting of Dendritic Spines by Cortical Pyramidal Neurons and Interneurons in Human Dorsolateral Prefrontal Cortex. Neuroscience 2020, 452: 181-191. PMID: 33212224, PMCID: PMC7770119, DOI: 10.1016/j.neuroscience.2020.10.022.Peer-Reviewed Original ResearchConceptsCortical pyramidal neuronsDorsolateral prefrontal cortexHuman dorsolateral prefrontal cortexPyramidal neuronsDendritic spinesDensity of spinesMonkey dorsolateral prefrontal cortexPrefrontal cortexPrimate dorsolateral prefrontal cortexDeep cortical layersPyramidal neuron activitySpecific neural circuitsGABAergic inputsGlutamatergic inputsGABAergic interneuronsGlutamatergic synapsesLaminar differencesCore cognitive functionNeuron activitySynaptic informationNeuron synapseCortical layersInterneuronsRecurrent excitationCognitive function
2017
[O2–02–03]: ULTRASTRUCTURAL EVIDENCE FOR IMPAIRED MITOCHONDRIAL FISSION IN THE AGED RHESUS MONKEY DORSOLATERAL PREFRONTAL CORTEX: RELEVANCE TO THE PATHOGENESIS OF ALZHEIMER's DISEASE
Datta D, Morozov Y, Paspalas A. [O2–02–03]: ULTRASTRUCTURAL EVIDENCE FOR IMPAIRED MITOCHONDRIAL FISSION IN THE AGED RHESUS MONKEY DORSOLATERAL PREFRONTAL CORTEX: RELEVANCE TO THE PATHOGENESIS OF ALZHEIMER's DISEASE. Alzheimer's & Dementia 2017, 13: p553-p553. DOI: 10.1016/j.jalz.2017.07.151.Peer-Reviewed Original Research
2016
Altered Expression of ARP2/3 Complex Signaling Pathway Genes in Prefrontal Layer 3 Pyramidal Cells in Schizophrenia
Datta D, Arion D, Roman K, Volk D, Lewis D. Altered Expression of ARP2/3 Complex Signaling Pathway Genes in Prefrontal Layer 3 Pyramidal Cells in Schizophrenia. American Journal Of Psychiatry 2016, 174: 163-171. PMID: 27523502, PMCID: PMC5288270, DOI: 10.1176/appi.ajp.2016.16020204.Peer-Reviewed Original ResearchConceptsLayer 3 pyramidal cellsDorsolateral prefrontal cortexPyramidal cellsParvalbumin interneuronsGray matterExcessive dopamine releaseDendritic spine densityCortical pyramidal cellsCommon final pathwayStriatal hyperdopaminergiaDLPFC gray matterVentral mesencephalonSpine deficitsSpine lossSpine densityExcitatory projectionsCognitive dysfunctionPairs of schizophreniaDopamine cellsDopamine releaseDendritic spinesComparison subjectsFinal pathwaySubcortical hyperdopaminergiaPrefrontal cortexLayer 3 Excitatory and Inhibitory Circuitry in the Prefrontal Cortex: Developmental Trajectories and Alterations in Schizophrenia
Hoftman G, Datta D, Lewis D. Layer 3 Excitatory and Inhibitory Circuitry in the Prefrontal Cortex: Developmental Trajectories and Alterations in Schizophrenia. Biological Psychiatry 2016, 81: 862-873. PMID: 27455897, PMCID: PMC5136518, DOI: 10.1016/j.biopsych.2016.05.022.Peer-Reviewed Original ResearchConceptsDorsolateral prefrontal cortexInhibitory gamma-aminobutyric acid (GABA) neuronsGamma-aminobutyric acid (GABA) neuronsPrefrontal cortexCertain clinical featuresExcitatory pyramidal neuronsAdverse environmental exposuresDisorders of neurodevelopmentNature of schizophreniaDLPFC circuitryInhibitory circuitryClinical featuresPyramidal neuronsDisease processDevelopmental refinementMemory impairmentMemory alterationsDevelopmental disturbancesNeural circuitrySchizophreniaEnvironmental exposuresLate developmental processesNeurodevelopmental disordersSpecific populationsAlterations
2015
Reciprocal Alterations in Regulator of G Protein Signaling 4 and microRNA16 in Schizophrenia
Kimoto S, Glausier J, Fish K, Volk D, Bazmi H, Arion D, Datta D, Lewis D. Reciprocal Alterations in Regulator of G Protein Signaling 4 and microRNA16 in Schizophrenia. Schizophrenia Bulletin 2015, 42: 396-405. PMID: 26424323, PMCID: PMC4753606, DOI: 10.1093/schbul/sbv139.Peer-Reviewed Original ResearchConceptsG protein-coupled receptorsDorsolateral prefrontal cortexG Protein Signaling 4Schizophrenia subjectsRGS4 mRNANMDAR hypofunctionNMDAR activityProtein levelsN-methyl-D-aspartate (NMDA) receptor hypofunctionRole of RGS4Pathology of schizophreniaHealthy comparison subjectsRGS4 mRNA levelsLevels of miR16RGS4 levelsProtein-coupled receptorsPyramidal neuronsReceptor hypofunctionPyramidal cellsComparison subjectsIncreased expressionHypofunctionPrefrontal cortexSchizophreniaMRNA levels
2014
Functional Maturation of GABA Synapses During Postnatal Development of the Monkey Dorsolateral Prefrontal Cortex
Gonzalez-Burgos G, Miyamae T, Pafundo D, Yoshino H, Rotaru D, Hoftman G, Datta D, Zhang Y, Hammond M, Sampson A, Fish K, Ermentrout G, Lewis D. Functional Maturation of GABA Synapses During Postnatal Development of the Monkey Dorsolateral Prefrontal Cortex. Cerebral Cortex 2014, 25: 4076-4093. PMID: 24904071, PMCID: PMC4626828, DOI: 10.1093/cercor/bhu122.Peer-Reviewed Original ResearchMeSH Keywords6-Cyano-7-nitroquinoxaline-2,3-dioneAge FactorsAlpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic AcidAnimalsAnimals, NewbornCalcium Channel BlockersExcitatory Amino Acid AgonistsExcitatory Amino Acid AntagonistsFemaleGABA AntagonistsGamma-Aminobutyric AcidInhibitory Postsynaptic PotentialsLysineMacaca mulattaModels, NeurologicalNeuronsOmega-Agatoxin IVAPrefrontal CortexPyridazinesSynapsesConceptsDorsolateral prefrontal cortexSynapse densityPyramidal cellsPrepubertal ageParvalbumin-positive GABA neuronsMonkey dorsolateral prefrontal cortexPrefrontal cortexPrimate dorsolateral prefrontal cortexInhibitory synapse densityInhibitory postsynaptic currentsAdult macaque monkeysCortical network activityDevelopment of GABAYoung adult ageDlPFC circuitsGamma frequency oscillationsGABA neuronsGABA synapsesInhibitory synaptogenesisPostsynaptic currentsPeripubertal periodSynaptic appositionsGamma band powerMacaque monkeysFunctional maturationDevelopmental Expression Patterns of GABAA Receptor Subunits in Layer 3 and 5 Pyramidal Cells of Monkey Prefrontal Cortex
Datta D, Arion D, Lewis D. Developmental Expression Patterns of GABAA Receptor Subunits in Layer 3 and 5 Pyramidal Cells of Monkey Prefrontal Cortex. Cerebral Cortex 2014, 25: 2295-2305. PMID: 24610118, PMCID: PMC4494034, DOI: 10.1093/cercor/bhu040.Peer-Reviewed Original ResearchConceptsGABAA receptor subunitsPyramidal cellsMonkey prefrontal cortexReceptor subunitsSubunit expressionLayer 3 pyramidal cellsGABAA receptor subunit expressionPrefrontal cortexGABAA receptor subunit mRNAsLayer 5 pyramidal cellsReceptor subunit changesPrefrontal pyramidal neuronsReceptor subunit expressionPyramidal neuron activityGlutamate receptor subunitsReceptor subunit mRNAsPyramidal cell firingPostnatal developmental changesPyramidal neuronsGABAA receptorsInhibitory inputsNeuron activityFunctional maturationPostnatal developmentCell firing