Featured Publications
Reward-Mediated, Model-Free Reinforcement-Learning Mechanisms in Pavlovian and Instrumental Tasks Are Related
Afshar N, Cinotti F, Martin D, Khamassi M, Calu DJ, Taylor JR, Groman SM. Reward-Mediated, Model-Free Reinforcement-Learning Mechanisms in Pavlovian and Instrumental Tasks Are Related. Journal Of Neuroscience 2022, 43: 458-471. PMID: 36216504, PMCID: PMC9864557, DOI: 10.1523/jneurosci.1113-22.2022.Peer-Reviewed Original ResearchConceptsGoal-tracking behaviorReinforcement learning mechanismInstrumental learning processesSign-tracking behaviorModel-free reinforcementApproach taskInstrumental taskInstrumental behaviorBehavioral proceduresSubjects designLearning mechanismDecision Making TaskModel-based computationLearning processModel-free reinforcement learningPredictive cuesIncentive salienceAssociative learningIndividual differencesComputational mechanismsDecision-making processPavlovianModel-based algorithmValue representationAction valuesExamining sex differences in responses to footshock stress and the role of the metabotropic glutamate receptor 5: an [18F]FPEB and positron emission tomography study in rats
Asch RH, Pothula S, Toyonaga T, Fowles K, Groman SM, Garcia-Milian R, DiLeone RJ, Taylor JR, Esterlis I. Examining sex differences in responses to footshock stress and the role of the metabotropic glutamate receptor 5: an [18F]FPEB and positron emission tomography study in rats. Neuropsychopharmacology 2022, 48: 489-497. PMID: 36100654, PMCID: PMC9852230, DOI: 10.1038/s41386-022-01441-y.Peer-Reviewed Original ResearchPositive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear
Lee B, Pothula S, Wu M, Kang H, Girgenti MJ, Picciotto MR, DiLeone RJ, Taylor JR, Duman RS. Positive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear. Molecular Psychiatry 2022, 27: 2580-2589. PMID: 35418600, PMCID: PMC9135632, DOI: 10.1038/s41380-022-01498-7.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderFear extinctionInfralimbic medial prefrontal cortexFear conditioning modelEnhanced fear extinctionFear-based behaviorsProlonged stress modelMedial prefrontal cortexSpontaneous recoveryIL-mPFCPTSD modelPTSD treatmentStress disorderPrefrontal cortexSPS modelN-methyl-D-aspartate receptor modulatorsBrain-derived neurotrophic factorN-methyl-D-aspartate receptorsBehavioral effectsIncreased attentionMPFCPreclinical findingsPyramidal neuronsNeurotrophic factorMale miceReinforcement Learning during Adolescence in Rats
Afshar N, Keip AJ, Taylor JR, Lee D, Groman SM. Reinforcement Learning during Adolescence in Rats. Journal Of Neuroscience 2020, 40: 5857-5870. PMID: 32601244, PMCID: PMC7380962, DOI: 10.1523/jneurosci.0910-20.2020.Peer-Reviewed Original ResearchConceptsNovel behavioral protocolReversal-learning performanceAdaptive choice behaviorBehavioral protocolFemale Long-Evans ratsReversal performanceChoice behaviorLong-Evans ratsAdolescent brain functionAge-related improvementsReinforcement-learning mechanismsReversal-learning taskReversal-learning paradigmDecision-making paradigmReinforcement learning mechanismAdolescent ratsLongitudinal designAge-related changesNeurodevelopmental mechanismsAdolescencePositive outcomesBrain functionFunction of circuitsPostnatal day 30AdulthoodMPEP Lowers Binge Drinking in Male and Female C57BL/6 Mice: Relationship with mGlu5/Homer2/Erk2 Signaling
Huang G, Thompson SL, Taylor JR. MPEP Lowers Binge Drinking in Male and Female C57BL/6 Mice: Relationship with mGlu5/Homer2/Erk2 Signaling. Alcohol Clinical And Experimental Research 2021, 45: 732-742. PMID: 33587295, PMCID: PMC8076072, DOI: 10.1111/acer.14576.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinge DrinkingDose-Response Relationship, DrugDrug Evaluation, PreclinicalExcitatory Amino Acid AntagonistsFemaleHomer Scaffolding ProteinsMaleMAP Kinase Signaling SystemMice, Inbred C57BLMitogen-Activated Protein Kinase 1Nucleus AccumbensPyridinesReceptor, Metabotropic Glutamate 5Septal NucleiSex CharacteristicsConceptsEffects of MPEPFemale C57BL/6 miceAlcohol intakeAlcohol consumptionNegative allosteric modulatorsLocomotor activityC57BL/6 miceFemale miceMale miceHomer2 expressionBinge drinkingMetabotropic glutamate receptor 5MGlu5 negative allosteric modulatorsSex differencesBinge alcohol consumptionGlutamate receptor 5Dose-response effectExcessive alcohol useERK2 expressionDose-response relationshipPotential sex differencesERK2 signalingBed nucleusNucleus accumbensStria terminalis
2023
Ketogenic diet enhances the effects of oxycodone in mice
Trinko R, Diaz D, Foscue E, Thompson S, Taylor J, DiLeone R. Ketogenic diet enhances the effects of oxycodone in mice. Scientific Reports 2023, 13: 7507. PMID: 37160959, PMCID: PMC10170077, DOI: 10.1038/s41598-023-33458-8.Peer-Reviewed Original ResearchConceptsOpioid use disorderKetogenic dietKD miceUse disordersTreatment of OUDEffects of KDEffects of oxycodoneClinical pain managementAlcohol use disorderProgressive ratio scheduleSex-specific effectsChronic oxycodoneLess oxycodoneOpioid withdrawalAntinociceptive effectPain managementPrescription opioidsSide effectsOxycodoneLocomotor activityTherapeutic potentialOpioidsDietary effectsOpiate sensitivityMice
2012
The tyrosine phosphatase STEP constrains amygdala-dependent memory formation and neuroplasticity
Olausson P, Venkitaramani D, Moran T, Salter M, Taylor J, Lombroso P. The tyrosine phosphatase STEP constrains amygdala-dependent memory formation and neuroplasticity. Neuroscience 2012, 225: 1-8. PMID: 22885232, PMCID: PMC3725644, DOI: 10.1016/j.neuroscience.2012.07.069.Peer-Reviewed Original ResearchMeSH KeywordsAmygdalaAnalysis of VarianceAnimalsBiophysicsConditioning, OperantElectric StimulationExcitatory Postsynaptic PotentialsFearMaleMAP Kinase Signaling SystemMemoryMiceMice, Inbred C57BLMice, TransgenicNeuronal PlasticityPatch-Clamp TechniquesProtein Tyrosine Phosphatases, Non-ReceptorReinforcement ScheduleReinforcement, PsychologyConceptsSynaptic plasticityExperience-dependent synaptic plasticityAspartic acid (NMDA) receptorsMemory formationLong-term potentiationAdult neuroplasticityAmygdala-dependent memory formationPharmacological treatmentKO miceExperience-induced neuroplasticityTyrosine phosphatase STEPNR2B subunitLateral amygdalaBrain regionsTyrosine kinase FynAcid receptorsStriatal-enriched protein tyrosine phosphataseNeuroplasticityMiceERK phosphorylationReceptor internalizationERK signalingKinase 1/2Detectable expressionSTEP KO mice
2009
Prior chronic cocaine exposure in mice induces persistent alterations in cognitive function
Krueger DD, Howell JL, Oo H, Olausson P, Taylor JR, Nairn AC. Prior chronic cocaine exposure in mice induces persistent alterations in cognitive function. Behavioural Pharmacology 2009, 20: 695-704. PMID: 19901826, PMCID: PMC3380449, DOI: 10.1097/fbp.0b013e328333a2bb.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAttentionCocaineCocaine-Related DisordersCognitionConditioning, ClassicalConditioning, OperantDisease Models, AnimalImpulsive BehaviorInhibition, PsychologicalInjections, IntraperitonealMaleMemory DisordersMemory, Short-TermMiceMice, Inbred C57BLMotor ActivityReinforcement ScheduleReinforcement, PsychologyReversal LearningTime FactorsConceptsCognitive functionAttentional functionsResponse inhibitionPrefrontal cortexThree-choice serial reaction time taskSerial reaction time taskReaction time taskPattern of errorsCocaine exposureDevelopment of addictionPrior chronic exposureCognitive flexibilityInstrumental reversalTime taskPosition taskChronic cocaine exposureChronic cocaine useCognitive dysfunctionTaskMemoryCocaine useDrug-free periodSuitable animal modelMultiple aspectsCortexPrelimbic cortex bdnf knock-down reduces instrumental responding in extinction
Gourley SL, Howell JL, Rios M, DiLeone RJ, Taylor JR. Prelimbic cortex bdnf knock-down reduces instrumental responding in extinction. Learning & Memory 2009, 16: 756-760. PMID: 19926781, PMCID: PMC2788209, DOI: 10.1101/lm.1547909.Peer-Reviewed Original ResearchNeuronal Correlates of Instrumental Learning in the Dorsal Striatum
Kimchi EY, Torregrossa MM, Taylor JR, Laubach M. Neuronal Correlates of Instrumental Learning in the Dorsal Striatum. Journal Of Neurophysiology 2009, 102: 475-489. PMID: 19439679, PMCID: PMC2712266, DOI: 10.1152/jn.00262.2009.Peer-Reviewed Original ResearchConceptsDorsal striatumResponse portsNeuronal activityTask-related firingTask-related neuronsMovement-related potentialsInitiation of movementLateral striatumLearning-related changesMedial striatumStriatumNeuronal correlatesReward portNumber of neuronsAcoustic stimuliNeuronsOperant taskField potentialsProgressive increaseLateral regionsTheta-band oscillationsHigh rateTraining periodInstrumental learningHead entries
2008
Acute Hippocampal Brain-Derived Neurotrophic Factor Restores Motivational and Forced Swim Performance After Corticosterone
Gourley SL, Kiraly DD, Howell JL, Olausson P, Taylor JR. Acute Hippocampal Brain-Derived Neurotrophic Factor Restores Motivational and Forced Swim Performance After Corticosterone. Biological Psychiatry 2008, 64: 884-890. PMID: 18675955, PMCID: PMC2633780, DOI: 10.1016/j.biopsych.2008.06.016.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorHippocampal brain-derived neurotrophic factorAntidepressant treatmentCORT exposureCORT secretionAppetitive instrumental behaviorChronic antidepressant treatmentDepressive-like stateNeurobiology of depressionHippocampal BDNF expressionAdult male miceAnhedonic-like behaviorResponse Element-Binding Protein PhosphorylationCAMP response element-binding protein (CREB) phosphorylationProgressive ratio taskElement-Binding Protein PhosphorylationADT efficacyCORT modelAntidepressant efficacyBDNF expressionHippocampal brainNeurotrophic factorSwim testCorticosterone exposureMale mice
2005
Persistent changes in motivation to self‐administer cocaine following modulation of cyclic AMP‐dependent protein kinase A (PKA) activity in the nucleus accumbens
Lynch W, Taylor J. Persistent changes in motivation to self‐administer cocaine following modulation of cyclic AMP‐dependent protein kinase A (PKA) activity in the nucleus accumbens. European Journal Of Neuroscience 2005, 22: 1214-1220. PMID: 16176364, DOI: 10.1111/j.1460-9568.2005.04305.x.Peer-Reviewed Original Research
2001
Embryonic ventral mesencephalic grafts to the substantia nigra of MPTP‐treated monkeys: Feasibility relevant to multiple‐target grafting as a therapy for Parkinson's disease
Collier TJ, Sortwell CE, Elsworth JD, Taylor JR, Roth RH, Sladek JR, Redmond DE. Embryonic ventral mesencephalic grafts to the substantia nigra of MPTP‐treated monkeys: Feasibility relevant to multiple‐target grafting as a therapy for Parkinson's disease. The Journal Of Comparative Neurology 2001, 442: 320-330. PMID: 11793337, DOI: 10.1002/cne.10108.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsBrain Tissue TransplantationCell DifferentiationChlorocebus aethiopsDopamineGraft SurvivalHomovanillic AcidImmunohistochemistryMaleNeostriatumNerve RegenerationNeuritesNeuronsParkinsonian DisordersRecovery of FunctionStem Cell TransplantationStem CellsSubstantia NigraTreatment OutcomeTyrosine 3-MonooxygenaseConceptsSubstantia nigraParkinson's diseaseDA neuronsVentral mesencephalonTyrosine hydroxylaseTH-positive fiber densityEmbryonic DA neuronsEmbryonic dopamine neuronsRostral substantia nigraStriatal DA depletionVentral mesencephalic graftsBasal ganglia circuitryBasal ganglia structuresSuboptimal therapeutic outcomesAfrican green monkeysDA modulationGrafted neuronsVM graftsMesencephalic graftsParkinsonian monkeysSN neuronsDA depletionReplacement therapyDA replacementDA levelsRepeated intermittent administration of psychomotor stimulant drugs alters the acquisition of Pavlovian approach behavior in rats: differential effects of cocaine, d-amphetamine and 3,4-methylenedioxymethamphetamine (“ecstasy”)
Taylor J, Jentsch J. Repeated intermittent administration of psychomotor stimulant drugs alters the acquisition of Pavlovian approach behavior in rats: differential effects of cocaine, d-amphetamine and 3,4-methylenedioxymethamphetamine (“ecstasy”). Biological Psychiatry 2001, 50: 137-143. PMID: 11526995, DOI: 10.1016/s0006-3223(01)01106-4.Peer-Reviewed Original ResearchEffects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5
Bibb J, Chen J, Taylor J, Svenningsson P, Nishi A, Snyder G, Yan Z, Sagawa Z, Ouimet C, Nairn A, Nestler E, Greengard P. Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5. Nature 2001, 410: 376-380. PMID: 11268215, DOI: 10.1038/35066591.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCocaineCocaine-Related DisordersCorpus StriatumCyclin-Dependent Kinase 5Cyclin-Dependent KinasesDopamineDopamine and cAMP-Regulated Phosphoprotein 32Enzyme InhibitorsGene Expression Regulation, EnzymologicKinetinMaleMiceMice, TransgenicNerve Tissue ProteinsNeuronsOligonucleotide Array Sequence AnalysisPhosphoproteinsPhosphorylationProto-Oncogene Proteins c-fosPsychomotor PerformancePurinesRatsRats, Sprague-DawleyReceptors, Dopamine D1RoscovitineSignal TransductionConceptsTranscription factorsSuch transcription factorsDownstream target genesCyclin-dependent kinase 5DNA array analysisTarget genesGene expressionCocaine administrationKinase 5Inducible transgenic miceChronic exposureCdk5 inhibitorMessenger RNACocaine addictionArray analysisDopamine-mediated neurotransmissionDopamine-containing nerve terminalsMedium spiny neuronsD1 dopamine receptorsChronic cocaine administrationOverexpression of ΔFosBProteinTransgenic miceAdaptive changesSpiny neuronsImpaired Inhibition of Conditioned Responses Produced by Subchronic Administration of Phencyclidine to Rats
Jentsch J, Taylor J. Impaired Inhibition of Conditioned Responses Produced by Subchronic Administration of Phencyclidine to Rats. Neuropsychopharmacology 2001, 24: 66-74. PMID: 11106877, DOI: 10.1016/s0893-133x(00)00174-3.Peer-Reviewed Original ResearchConceptsPCP-treated ratsStimulus-reward associationsNovel instrumental responseInhibitory response controlObsessive-compulsive disorderMore responsesConcurrent discriminationReversal learningFrontostriatal systemIncentive stimuliAffective impairmentsInhibitory controlInstrumental respondingImpaired inhibitionConditioned responseInstrumental responsePCP treatmentResponse controlMental disordersCurrent studyDrug abuseStimuliLearningSubchronic administrationImpulsivity
2000
Object retrieval/detour deficits in monkeys produced by prior subchronic phencyclidine administration: evidence for cognitive impulsivity
Jentsch J, Roth R, Taylor J. Object retrieval/detour deficits in monkeys produced by prior subchronic phencyclidine administration: evidence for cognitive impulsivity. Biological Psychiatry 2000, 48: 415-424. PMID: 10978725, DOI: 10.1016/s0006-3223(00)00926-4.Peer-Reviewed Original ResearchConceptsPhencyclidine administrationObject retrieval detour taskFrontal cortical dysfunctionFrontal cortex ablationSubchronic phencyclidine administrationPerformance of trialsDrugs of abusePhencyclidine exposureSubchronic administrationIntermittent administrationCortical dysfunctionDrug withdrawalChronic consumptionDopaminergic dysfunctionBehavioral deficitsPsychotomimetic drugsCorticostriatal functionInhibitory response controlCognitive impairmentImpaired acquisitionNonhuman primatesAdministrationPhencyclidineDysfunctionInhibitory control
1999
Striatal dopaminergic correlates of stable parkinsonism and degree of recovery in old-world primates one year after MPTP treatment
Elsworth J, Taylor J, Sladek J, Collier T, Redmond D, Roth R. Striatal dopaminergic correlates of stable parkinsonism and degree of recovery in old-world primates one year after MPTP treatment. Neuroscience 1999, 95: 399-408. PMID: 10658619, DOI: 10.1016/s0306-4522(99)00437-6.Peer-Reviewed Original ResearchConceptsHomovanillic acid/dopamine ratioMPTP treatmentStriatal dopamine levelsDopamine levelsDopamine lossDopamine depletionDopamine ratioStriatal subregionsNucleus accumbensCaudate nucleusDopamine concentrationsOne-yearSeverity categoriesDopamine neuron integrityVentromedial caudate nucleusStriatal dopamine lossHomovanillic acid concentrationsStriatal dopaminergic functionMarked increaseNormal motor performancePaucity of dataMetabolic activityNon-human primatesParkinsonian disabilityTetrahydropyridine (MPTP) modelA role for norepinephrine in stress-induced cognitive deficits: α-1-adrenoceptor mediation in the prefrontal cortex
Birnbaum S, Gobeske K, Auerbach J, Taylor J, Arnsten A. A role for norepinephrine in stress-induced cognitive deficits: α-1-adrenoceptor mediation in the prefrontal cortex. Biological Psychiatry 1999, 46: 1266-1274. PMID: 10560032, DOI: 10.1016/s0006-3223(99)00138-9.Peer-Reviewed Original ResearchConceptsStress-induced cognitive deficitsPoor attention regulationAlternation performanceSpatial working memoryPFC cognitive functionPrefrontal cortical dysfunctionMotor response timeIntra-PFC infusionsStress-induced deficitsStress-induced impairmentWorking memoryAttention regulationPFC contributeMemory performanceAlternation testingStress researchNeuropsychiatric disordersPrefrontal cortexCognitive deficitsCognitive functionMemory functionMemory impairmentPFC dysfunctionPerseverative patternsPharmacological stressorSpontaneous Blink Rates Correlate with Dopamine Levels in the Caudate Nucleus of MPTP-Treated Monkeys
Taylor J, Elsworth J, Lawrence M, Sladek J, Roth R, Redmond D. Spontaneous Blink Rates Correlate with Dopamine Levels in the Caudate Nucleus of MPTP-Treated Monkeys. Experimental Neurology 1999, 158: 214-220. PMID: 10448434, DOI: 10.1006/exnr.1999.7093.Peer-Reviewed Original ResearchConceptsCaudate nucleusConcentration of DAEye blink rateBlink rateDA ratioDopaminergic regulationD1 agonist dihydrexidineDA D2 receptorsDopaminergic neurotoxin MPTPSeverity of parkinsonismSpontaneous eye blink rateSpecific brain regionsAntiparkinsonian effectsDA depletionD2 agonistDopamine D1Dopamine levelsNeurotoxin MPTPD2 receptorsMPTPNormal animalsRostral portionSubcortical regionsBrain regionsVentromedial region