Amy Arnsten, PhD
Albert E. Kent Professor of Neuroscience and Professor of PsychologyCards
Additional Titles
Member, Kavli Institute of Neuroscience at Yale University
Contact Info
Neuroscience
PO Box 208001, 333 Cedar Street
New Haven, CT 06520-8001
United States
Appointments
Additional Titles
Member, Kavli Institute of Neuroscience at Yale University
Contact Info
Neuroscience
PO Box 208001, 333 Cedar Street
New Haven, CT 06520-8001
United States
Appointments
Additional Titles
Member, Kavli Institute of Neuroscience at Yale University
Contact Info
Neuroscience
PO Box 208001, 333 Cedar Street
New Haven, CT 06520-8001
United States
About
Titles
Albert E. Kent Professor of Neuroscience and Professor of Psychology
Member, Kavli Institute of Neuroscience at Yale University
Biography
Dr. Arnsten is an international expert on the molecular regulation of higher cortical circuits, and a member of the National Academy of Medicine. She received her B.A. in Neuroscience from Brown University in 1976 (where she created the Neuroscience major), and her Ph.D. in Neuroscience from UCSD in 1981. She did post-doctoral research with Dr. Susan Iversen at Cambridge University in the UK, and with Dr. Patricia Goldman-Rakic at Yale. Dr. Arnsten's research examines the neural basis of higher cognition. Her work has revealed that the newly evolved cortical circuits that underlie higher cognition are uniquely regulated at the molecular level, conferring vulnerability in mental illness and age-related cognitive disorders such as Alzheimer's Disease. Arnsten's research has led to new treatments for cognitive disorders in humans, including the successful translation of guanfacine (IntunivTM) for the treatment of ADHD and related prefrontal cortical disorders.
Appointments
Neuroscience
ProfessorPrimaryChild Study Center
ProfessorSecondaryDepartment of Psychology
ProfessorSecondaryPsychiatry
ProfessorSecondary
Other Departments & Organizations
- Alzheimer's Disease Research Center (ADRC)
- Arnsten Lab
- Center for Brain & Mind Health
- Child Study Center
- Department of Psychology
- Interdepartmental Neuroscience Program
- Kavli Institute for Neuroscience
- Neural Disorders
- Neuroscience
- Neuroscience Research Training Program (NRTP)
- Neuroscience Track
- Psychiatry
- WHRY Pilot Project Program Investigators
- Women's Health Research at Yale
- Wu Tsai Institute
- Yale Center for Research on Aging (Y-Age)
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Stress Center
- Yale Ventures
Education & Training
- PhD
- University of California, San Diego (1981)
Research
Overview
The Arnsten Lab studies molecular influences on the higher cognitive functions of the prefrontal cortex (PFC), with the overarching goal of developing rational treatments for cognitive disorders and mental illness. The lab uses a multi-disciplinary approach to understand mechanisms influencing working memory at the cellular and behavioral levels. Research has focused on how the arousal pathways rapidly alter PFC network strength through intracellular signaling mechanisms, a process termed Dynamic Network Connectivity. Our data explain how exposure to stress and/or inflammation causes the rapid loss of PFC cognitive abilities, and how genetic mutations in molecules that regulate these pathways can lead to symptoms of mental illness. Dysregulation of these pathways with advancing age leads to loss of neuronal firing, cognitive impairments,and increased vulnerability for degeneration including tau pathology in Alzheimer's disease. Understanding these mechanisms has led to successful new treatments for patients with PFC dysfunction, including medications for Attention Deficit Hyperactivity Disorder, Post-Traumatic Stress Disorder, long-COVID and delirium.
Medical Research Interests
Public Health Interests
ORCID
0000-0002-3420-1308- View Lab Website
Arnsten Lab
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Dibyadeep Datta
Christopher van Dyck, MD
Yury M. Morozov, PhD
Min Wang, PhD
Alvaro Duque, PhD
Juan Arellano, PhD
Prefrontal Cortex
Aging
Schizophrenia
Alzheimer Disease
Stress Disorders, Post-Traumatic
Publications
2024
Characterizing 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, DOI: 10.1176/appi.ajp.20240731.Peer-Reviewed Original ResearchMeSH KeywordsKey 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 ResearchConceptsDorsolateral 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 riskStress and inflammation target dorsolateral prefrontal cortex function: Neural mechanisms underlying weakened cognitive control
Joyce M, Uchendu S, Arnsten A. Stress and inflammation target dorsolateral prefrontal cortex function: Neural mechanisms underlying weakened cognitive control. Biological Psychiatry 2024 PMID: 38944141, DOI: 10.1016/j.biopsych.2024.06.016.Peer-Reviewed Original ResearchConceptsMental disordersDorsolateral prefrontal cortex functionPrefrontal cortex functionSubgenual cingulate cortexRegulate emotional responsesDorsolateral prefrontal cortexChronic stress exposurePosterior association cortexMedial PFCCognitive controlPrefrontal cortexWorking memoryCingulate cortexRegulate attentionCortex functionNeural mechanismsDlPFCBrain regionsStress exposureAssociation cortexTop-down projectionsEmotional responsesSpine lossArousal statePersistent firingThe 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 ResearchMeSH Keywords and ConceptsConceptsInter-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 ResearchConceptsDorsolateral 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 ResearchCombined Use of Guanfacine and N-Acetylcysteine for the Treatment of Cognitive Deficits After Traumatic Brain Injury
Khasnavis S, Belliveau T, Arnsten A, Fesharaki-Zadeh A. Combined Use of Guanfacine and N-Acetylcysteine for the Treatment of Cognitive Deficits After Traumatic Brain Injury. Neurotrauma Reports 2024, 5: 226-231. PMID: 38524728, PMCID: PMC10960163, DOI: 10.1089/neur.2023.0124.Peer-Reviewed Original ResearchConceptsTreatment of cognitive deficitsTraumatic brain injuryExecutive functionCognitive deficitsTraumatic brain injury clinicEfficacy of guanfacinePre-frontal cortexBrain injuryTreat traumatic brain injuryBehavioral therapyNeuropsychological testsCognitive symptomsCognitive changesPlacebo-controlled trialProcessing speedGuanfacineCortical functionOpen-label useApproved medicationsPersonsPost-treatmentDeficitsTraumatizationN-acetylcysteineMTBIDynamic 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 ResearchConceptsDynamic 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 spinesInhibition of brain glutamate carboxypeptidase II (GCPII) to enhance cognitive function
Wiseman R, Bigos K, Arnsten A, Slusher B. Inhibition of brain glutamate carboxypeptidase II (GCPII) to enhance cognitive function. Advances In Pharmacology 2024 DOI: 10.1016/bs.apha.2024.10.018.Peer-Reviewed Original ResearchConceptsN-acetylaspartyl glutamateGlutamate carboxypeptidase IICognitive deficitsCognitive functionDorsolateral prefrontal cortex of primatesPrefrontal cortex of primatesHigher order cognitive processesDorsolateral prefrontal cortexMetabotropic glutamate receptor 3Inhibition of glutamate carboxypeptidase IIImprove cognitive deficitsEnhance cognitive functionImprove cognitive performanceEnzyme glutamate carboxypeptidase IIGlutamate receptor 3Executive functionCortex of primatesMGlu3 receptorsCarboxypeptidase IICognitive performanceCognitive processesPersistent neuronal firingClinical populationsNeuronal firingClinical workThe circuit mechanisms of working memory: Key roles of the dorsolateral prefrontal cortex
Arnsten A, Martinez-Trujillo J. The circuit mechanisms of working memory: Key roles of the dorsolateral prefrontal cortex. 2024 DOI: 10.1016/b978-0-443-15754-7.00038-9.Peer-Reviewed Original ResearchConceptsDorsolateral prefrontal cortexPrefrontal cortexWorking memoryMechanisms of working memorySpatial working memoryPosterior association cortexExecutive functionMediodorsal thalamusSketch padMental representationsAssociation cortexSubcortical connectionsCholinergic neurotransmissionCircuit mechanismsRecurrent excitatory circuitsNMDA receptorsAbstract thoughtPersistent firingPrimate researchCortexDlPFCExcitatory circuitsMemorySensory stimulationAlzheimer's disease
Academic Achievements & Community Involvement
honor Member, National Academy of Medicine
National AwardDetails10/07/2017United Stateshonor Goldman-Rakic Prize for Outstanding Achievement in Cognitive Neuroscience
National AwardDetails07/25/2015United States
News & Links
Media
News
- August 05, 2024Source: CNN
You really can think so hard it hurts. Here's what to do about it
- August 05, 2024Source: CNN
You really can think so hard it hurts. Here's what to do about it | CNN
- June 10, 2024
Study Reveals How Calcium Channel Mutations Lead to Cognitive Dysfunction
- June 05, 2024
Four Faculty Invited to Speak at Cold Spring Harbor's 2024 Schizophrenia and Related Disorders Course
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Neuroscience
PO Box 208001, 333 Cedar Street
New Haven, CT 06520-8001
United States