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 riskβ1-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 biomarkersInterrogating 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 ResearchMacaque dorsolateral prefrontal cortexDorsolateral prefrontal cortexSchizophrenia risk genesAnatomical evaluationPrefrontal cortexRisk genesCortex
2021
Studies 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 ResearchMacaque dorsolateral prefrontal cortexDorsolateral prefrontal cortexSchizophrenia risk genesPrefrontal cortexRisk genes
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 mechanismThe 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 etiologyMapping 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 maturation