2024
Ventral hippocampal parvalbumin interneurons gate the acute anxiolytic action of the serotonergic psychedelic DOI
Tiwari P, Davoudian P, Kapri D, Vuruputuri R, Karaba L, Sharma M, Zanni G, Balakrishnan A, Chaudhari P, Pradhan A, Suryavanshi S, Bath K, Ansorge M, Fernandez-Ruiz A, Kwan A, Vaidya V. Ventral hippocampal parvalbumin interneurons gate the acute anxiolytic action of the serotonergic psychedelic DOI. Neuron 2024 PMID: 39321791, DOI: 10.1016/j.neuron.2024.08.016.Peer-Reviewed Original ResearchAnxiolytic actionVentral hippocampusParvalbumin (PV)-positive interneuronsAnxiety-like behaviorAction of DOIPV-positive interneuronsPsychedelic DOIAnxiolytic responseAnxiolytic effectsSerotonergic psychedelicsFast-spiking cellsParvalbumin interneuronsGABAergic interneuronsVHPCFiring rateDOIHippocampusInterneuronsTherapeutic potentialReceptorsPsychedelicsCellular triggersGenetic approachesElectrophysiologyPsilocybin Facilitates Fear Extinction: Importance of Dose, Context, and Serotonin Receptors
Woodburn S, Levitt C, Koester A, Kwan A. Psilocybin Facilitates Fear Extinction: Importance of Dose, Context, and Serotonin Receptors. ACS Chemical Neuroscience 2024, 15: 3034-3043. PMID: 39087917, DOI: 10.1021/acschemneuro.4c00279.Peer-Reviewed Original ResearchPost-traumatic stress disorderFear extinctionFear renewalExtinction retentionSerotonin receptorsPsilocybin effectsEffects of psilocybinExtinction-based therapiesProlonged exposure therapyFear conditioning paradigmAnalysis of sex differencesEnhanced fear extinctionFear learning paradigmAdministration of psilocybinConditioning paradigmExposure therapyFear learningStress disorderClassic psychedelicsPsilocybinSex differencesExtinction experimentsReceptor antagonismDrug effectsSerotoninSpatiotemporal Organization of Prefrontal Norepinephrine Influences Neuronal Activity
Glaeser-Khan S, Savalia N, Cressy J, Feng J, Li Y, Kwan A, Kaye A. Spatiotemporal Organization of Prefrontal Norepinephrine Influences Neuronal Activity. ENeuro 2024, 11: eneuro.0252-23.2024. PMID: 38702188, PMCID: PMC11134306, DOI: 10.1523/eneuro.0252-23.2024.Peer-Reviewed Original ResearchTwo-photon imagingLocus coeruleusPrefrontal cortexOptical flow analysisIn vivo two-photon imagingInfluence neuronal activityVesicle exocytosisControl of cortical activityNE releaseGPCR-based sensorsNE dynamicsLocal fieldNeuronal calciumNeuronal firingCell firingNE roleNorepinephrineHomogeneous fieldNeuronal activitySpatiotemporal activity patternsNeurotransmitter functionSensorLight-sheet imagingAxonal dynamicsSpatial scales
2023
Dynamic Foraging Behavior Performance Is Not Affected by Scn2a Haploinsufficiency
Schamiloglu S, Wu H, Zhou M, Kwan A, Bender K. Dynamic Foraging Behavior Performance Is Not Affected by Scn2a Haploinsufficiency. ENeuro 2023, 10: eneuro.0367-23.2023. PMID: 38151324, PMCID: PMC10755640, DOI: 10.1523/eneuro.0367-23.2023.Peer-Reviewed Original ResearchTiming is key for behavioural benefits of psychedelics
Woodburn S, Kwan A. Timing is key for behavioural benefits of psychedelics. Nature 2023, 618: 677-678. PMID: 37316593, DOI: 10.1038/d41586-023-01869-2.Peer-Reviewed Original ResearchHyperconnectivity of Two Separate Long-Range Cholinergic Systems Contributes to the Reorganization of the Brain Functional Connectivity during Nicotine Withdrawal in Male Mice
Carrette L, Kimbrough A, Davoudian P, Kwan A, Collazo A, George O. Hyperconnectivity of Two Separate Long-Range Cholinergic Systems Contributes to the Reorganization of the Brain Functional Connectivity during Nicotine Withdrawal in Male Mice. ENeuro 2023, 10: eneuro.0019-23.2023. PMID: 37295945, PMCID: PMC10306126, DOI: 10.1523/eneuro.0019-23.2023.Peer-Reviewed Original ResearchConceptsWhole-brain functional connectivityCholinergic regionsCholinergic systemFunctional connectivityNicotine withdrawalMale miceFos expressionNicotinic receptorsBrain cholinergic systemWithdrawal-induced changesImmediate early gene FosDiscontinuation of useNicotinic acetylcholine receptorsBrain functional connectivityCholinergic neuronsBasal forebrainNicotine resultsWithdrawal symptomsCholinergic neurotransmissionMRNA expression databaseReceptor mRNANicotine dependenceAcetylcholine receptorsBaseline expressionBrain regionsA computational model for learning from repeated traumatic experiences under uncertainty
Kaye A, Rao M, Kwan A, Ressler K, Krystal J. A computational model for learning from repeated traumatic experiences under uncertainty. Cognitive, Affective, & Behavioral Neuroscience 2023, 23: 894-904. PMID: 37165181, PMCID: PMC11149767, DOI: 10.3758/s13415-023-01085-5.Peer-Reviewed Original ResearchPosttraumatic stress disorderTraumatic eventsNovel contextThreat perceptionTreatment of PTSDEarly life traumaNeutral cuesThreat responsesStress disorderLife traumaTraumatic experiencesPrediction errorComputational theorySensory cuesPTSD incidenceNovel predictionsUnpredictable footshockInternal statesComputational modelCuesPerceptionSpecific associationFootshockContextTheoryCircuit- and Behavioral- Level Investigation of Plasticity After Administration of Entactogens in Mice
Kaye A, Kwan A, Pittenger C, Yu A, Yang J. Circuit- and Behavioral- Level Investigation of Plasticity After Administration of Entactogens in Mice. Biological Psychiatry 2023, 93: s57. DOI: 10.1016/j.biopsych.2023.02.156.Peer-Reviewed Original ResearchCompetitive and cooperative games for probing the neural basis of social decision-making in animals
Wang H, Kwan A. Competitive and cooperative games for probing the neural basis of social decision-making in animals. Neuroscience & Biobehavioral Reviews 2023, 149: 105158. PMID: 37019249, PMCID: PMC10175234, DOI: 10.1016/j.neubiorev.2023.105158.Peer-Reviewed Original Research5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice
Jefferson S, Gregg I, Dibbs M, Liao C, Wu H, Davoudian P, Woodburn S, Wehrle P, Sprouse J, Sherwood A, Kaye A, Pittenger C, Kwan A. 5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice. Neuropsychopharmacology 2023, 48: 1257-1266. PMID: 37015972, PMCID: PMC10354037, DOI: 10.1038/s41386-023-01572-w.Peer-Reviewed Original ResearchConceptsMouse medial frontal cortexEarly phase clinical studiesDendritic spine densityHead-twitch responseDose-dependent increaseStructural neural plasticityMedial frontal cortexSpine densityClinical studiesFrontal cortexLong-term effectsDendritic spinesMental illnessNeural plasticitySpine formationPatient accessSubjective effectsNeural consequencesPotential therapeuticsSerotonergic psychedelicsAnxiety symptomsNeural mechanismsUltrasonic vocalizationsElevated ratesMiceShared and Distinct Brain Regions Targeted for Immediate Early Gene Expression by Ketamine and Psilocybin
Davoudian P, Shao L, Kwan A. Shared and Distinct Brain Regions Targeted for Immediate Early Gene Expression by Ketamine and Psilocybin. ACS Chemical Neuroscience 2023, 14: 468-480. PMID: 36630309, PMCID: PMC9898239, DOI: 10.1021/acschemneuro.2c00637.Peer-Reviewed Original ResearchConceptsC-fos expressionBrain regionsNeural plasticityPlasticity-related gene expressionPrimary visual cortexNumerous brain regionsAnterior cingulate cortexExact brain regionsContribution of receptorsDistinct brain regionsImmediate early gene expressionDorsal rapheGlutamatergic receptorsCA1 subfieldSubanesthetic ketamineFemale miceLocus coeruleusInsular cortexSaline controlsTherapeutic effectPsilocybin administrationBasolateral amygdalaLateral habenulaCingulate cortexVisual cortex
2022
Psychedelics and Neural Plasticity: Therapeutic Implications
Grieco S, Castrén E, Knudsen G, Kwan A, Olson D, Zuo Y, Holmes T, Xu X. Psychedelics and Neural Plasticity: Therapeutic Implications. Journal Of Neuroscience 2022, 42: 8439-8449. PMID: 36351821, PMCID: PMC9665925, DOI: 10.1523/jneurosci.1121-22.2022.Peer-Reviewed Original ResearchConceptsTherapeutic effectNeural plasticityUnmet clinical needFunctional neural plasticityBrain-wide circuitsPsychedelic drugsClinical trialsBasic neuroscience questionsReceptor binding sitesTherapeutic implicationsBrain disordersClinical researchPsychedelic effectsBrain functionClinical needEffects of psychedelicsDrugsNeural mechanismsFuture studiesPsychedelicsGene expressionNeuroscience questionsClinicTrialsThe neural basis of psychedelic action
Kwan A, Olson D, Preller K, Roth B. The neural basis of psychedelic action. Nature Neuroscience 2022, 25: 1407-1419. PMID: 36280799, PMCID: PMC9641582, DOI: 10.1038/s41593-022-01177-4.Peer-Reviewed Original ResearchConceptsSerotonin 2A receptor agonistThalamocortical functional connectivityDownstream molecular signaling pathwaysDrug discoveryMolecular signaling pathwaysReceptor agonistSerotonin receptorsAssociation cortexPsychedelic actionSustained effectSubcortical regionsBasic neurobiologyFunctional connectivityTranscriptional changesPsychoactive moleculesSignaling pathwaysNeural mechanismsStructural plasticityNeural basisPsychedelic drugsChemistryPsychedelicsEnduring effectMoleculesAgonists
2021
Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo
Shao LX, Liao C, Gregg I, Davoudian PA, Savalia NK, Delagarza K, Kwan AC. Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo. Neuron 2021, 109: 2535-2544.e4. PMID: 34228959, PMCID: PMC8376772, DOI: 10.1016/j.neuron.2021.06.008.Peer-Reviewed Original ResearchConceptsFrontal cortexDendritic spinesMouse medial frontal cortexLayer 5 pyramidal neuronsSpine formation ratesApical dendritic spinesMedial frontal cortexUntapped therapeutic potentialPyramidal neuronsSingle doseExcitatory neurotransmissionBehavioral deficitsBeneficial actionsStructural remodelingSynaptic rewiringMammalian brainTherapeutic potentialNeural adaptationUse of psychedelicsSerotonergic psychedelicsSpine sizeTwo-photon microscopyCortexPsilocybinSpine
2020
A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics
Savalia NK, Shao LX, Kwan AC. A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics. Trends In Neurosciences 2020, 44: 260-275. PMID: 33358035, PMCID: PMC7990695, DOI: 10.1016/j.tins.2020.11.008.BooksKetamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines
Ali F, Gerhard DM, Sweasy K, Pothula S, Pittenger C, Duman RS, Kwan AC. Ketamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines. Nature Communications 2020, 11: 72. PMID: 31911591, PMCID: PMC6946708, DOI: 10.1038/s41467-019-13809-8.Peer-Reviewed Original ResearchConceptsDendritic spinesN-methyl-D-aspartate receptor antagonistPrefrontal cortexPrefrontal dendritic spinesApical dendritic spinesSomatostatin-expressing (SST) interneuronsCortico-cortical connectivityElevated calcium levelsMedial prefrontal cortexKetamine actsAntidepressant effectsGABAergic neuronsSST interneuronsKetamine actionPyramidal neuronsNMDAR antagonismReceptor antagonistSubanesthetic ketamineSubanesthetic doseDendritic inhibitionAwake miceCortical interneuronsSynaptic inputsCalcium levelsCalcium transients