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
Chronic 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 dysregulationLocalization 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
2020
Classical complement cascade initiating C1q protein within neurons in the aged rhesus macaque dorsolateral prefrontal cortex
Datta D, Leslie SN, Morozov YM, Duque A, Rakic P, van Dyck CH, Nairn AC, Arnsten AFT. Classical complement cascade initiating C1q protein within neurons in the aged rhesus macaque dorsolateral prefrontal cortex. Journal Of Neuroinflammation 2020, 17: 8. PMID: 31906973, PMCID: PMC6945481, DOI: 10.1186/s12974-019-1683-1.Peer-Reviewed Original ResearchConceptsRat medial PFCPrimate dlPFCC1q levelsMedial PFCLayer IIIC1q proteinPrecise anatomical distributionMacaque dorsolateral prefrontal cortexAge-related degenerationDorsolateral prefrontal cortexAge-related changesC1q expressionSynapse lossBackgroundCognitive impairmentSpine lossComplement signalingInhibitory synapsesAnatomical distributionSynaptic localizationDisease pathogenesisGlial phagocytosisAlzheimer's diseaseClassical complementPrimate cortexPrefrontal cortex
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
2013
Role of disrupted in schizophrenia 1 (DISC1) in stress-induced prefrontal cognitive dysfunction
Gamo NJ, Duque A, Paspalas CD, Kata A, Fine R, Boven L, Bryan C, Lo T, Anighoro K, Bermudez L, Peng K, Annor A, Raja A, Mansson E, Taylor SR, Patel K, Simen AA, Arnsten AF. Role of disrupted in schizophrenia 1 (DISC1) in stress-induced prefrontal cognitive dysfunction. Translational Psychiatry 2013, 3: e328-e328. PMID: 24301646, PMCID: PMC4030323, DOI: 10.1038/tp.2013.104.Peer-Reviewed Original ResearchConceptsPrefrontal cortexCyclic adenosine monophosphateMental illnessRestraint stressCognitive dysfunctionControl groupStress-induced cognitive dysfunctionPhosphodiesterase 4Schizophrenia 1Prefrontal cognitive dysfunctionMild restraint stressH restraint stressUnoperated control groupKD ratsDISC1 mutationViral knockdownNormal animalsPFC dysfunctionImpair functionIncreases SusceptibilityDysfunctionDISC1 geneIllnessCAMP levelsMultifunctional scaffolding protein
2009
Circuit-based Localization of Ferret Prefrontal Cortex
Duque A, McCormick DA. Circuit-based Localization of Ferret Prefrontal Cortex. Cerebral Cortex 2009, 20: 1020-1036. PMID: 19737780, PMCID: PMC2852501, DOI: 10.1093/cercor/bhp164.Peer-Reviewed Original Research
2007
α2A-Adrenoceptors Strengthen Working Memory Networks by Inhibiting cAMP-HCN Channel Signaling in Prefrontal Cortex
Wang M, Ramos BP, Paspalas CD, Shu Y, Simen A, Duque A, Vijayraghavan S, Brennan A, Dudley A, Nou E, Mazer JA, McCormick DA, Arnsten AF. α2A-Adrenoceptors Strengthen Working Memory Networks by Inhibiting cAMP-HCN Channel Signaling in Prefrontal Cortex. Cell 2007, 129: 397-410. PMID: 17448997, DOI: 10.1016/j.cell.2007.03.015.Peer-Reviewed Original ResearchConceptsHCN channel blockadePrefrontal cortical neuronsDelay-related firingΑ2A adrenoceptorsChannel blockadeCortical neuronsInhibition of cAMPAlpha2A adrenoceptorsDendritic spinesNetwork firingElectrophysiological studiesPFC neuronsRecurrent excitationFunctional connectivityHCN channelsPrefrontal cortexHCN1 channelsPFC networksCAMP inhibitionStimulationBlockade
2006
Neocortical Network Activity In Vivo Is Generated through a Dynamic Balance of Excitation and Inhibition
Haider B, Duque A, Hasenstaub A, McCormick D. Neocortical Network Activity In Vivo Is Generated through a Dynamic Balance of Excitation and Inhibition. Journal Of Neuroscience 2006, 26: 4535-4545. PMID: 16641233, PMCID: PMC6674060, DOI: 10.1523/jneurosci.5297-05.2006.Peer-Reviewed Original ResearchConceptsCerebral cortexNeocortical network activityReversal potentialUp statesPersistent network activityNetwork activityDepolarized reversal potentialSpontaneous network activityField potential recordingsLocal cortical circuitsLocal field potential recordingsNeuronal responsivenessCortical functionRecurrent excitatoryCortical circuitsSynaptic currentsPotential recordingsRecurrent excitationExcitatory conductancePrefrontal cortexInhibitory connectionsCortexStable network statesSlow oscillationsInhibition