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 riskDynamic 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 spines
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
2017
mGluR2 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 disease
2015
Dopamine’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
2012
Guanfacine for the treatment of cognitive disorders: a century of discoveries at Yale.
Arnsten AF, Jin LE. Guanfacine for the treatment of cognitive disorders: a century of discoveries at Yale. The Yale Journal Of Biology And Medicine 2012, 85: 45-58. PMID: 22461743, PMCID: PMC3313539.Peer-Reviewed Original ResearchConceptsAttention deficit hyperactivity disorderPrefrontal cortexCognitive disordersHigher-order cognitive abilitiesDeficit hyperactivity disorderPFC cognitive functionCognitive abilitiesHyperactivity disorderCognitive functionMemory functionPFC functionAgonist guanfacineBrain regionsGuanfacineRecent researchNeurobiologyYale Medical SchoolCentury of discoveryDisordersTherapeutic targetTourette syndromePostsynaptic spinesEmotionsMemorySyndrome
2010
Dynamic Network Connectivity: A new form of neuroplasticity
Arnsten AF, Paspalas CD, Gamo NJ, Yang Y, Wang M. Dynamic Network Connectivity: A new form of neuroplasticity. Trends In Cognitive Sciences 2010, 14: 365-375. PMID: 20554470, PMCID: PMC2914830, DOI: 10.1016/j.tics.2010.05.003.Peer-Reviewed Original Research
2007
Norepinephrine and cognitive disorders
Arnsten A. Norepinephrine and cognitive disorders. 2007, 408-435. DOI: 10.1017/cbo9780511544156.015.Peer-Reviewed Original ResearchNoradrenergic drugsCentral nervous system norepinephrineNervous system norepinephrineRole of norepinephrineNoradrenergic neuronsCNS diseaseTherapeutic effectCognitive disordersNorepinephrineNeurological disordersNorepinephrine's roleBrain diseasesNew disease indicationsChemical neurotransmittersDisease indicationsDrugsDiseasePharmacologyDisordersTherapeuticsBasic biologyMolecular biologyNeurotransmittersNeuronsBrain
1998
Catecholamine modulation of prefrontal cortical cognitive function
Arnsten A. Catecholamine modulation of prefrontal cortical cognitive function. Trends In Cognitive Sciences 1998, 2: 436-447. PMID: 21227275, DOI: 10.1016/s1364-6613(98)01240-6.Peer-Reviewed Original ResearchAttention deficit hyperactivity disorderPrefrontal cortexCognitive functionPrefrontal cortical cognitive functionUncontrollable stressCortical cognitive functionsWorking Memory FunctionDeficit hyperactivity disorderHyperactivity disorderPFC functionPFC dysfunctionNormal agingCognitive disordersCatecholamine modulationDopamine systemNeurochemical influencesMental disordersNeuropsychiatric disordersDisordersEnvironmental cuesCuesNeuromodulatory inputsMemoryFresh understandingHigh levels