Featured Publications
Brain responses to nutrients are severely impaired and not reversed by weight loss in humans with obesity: a randomized crossover study
van Galen K, Schrantee A, ter Horst K, la Fleur S, Booij J, Constable R, Schwartz G, DiLeone R, Serlie M. Brain responses to nutrients are severely impaired and not reversed by weight loss in humans with obesity: a randomized crossover study. Nature Metabolism 2023, 5: 1059-1072. PMID: 37308722, DOI: 10.1038/s42255-023-00816-9.Peer-Reviewed Original ResearchConceptsDiet-induced weight lossCerebral neuronal activityStriatal dopamine releaseWeight lossCrossover studyDopamine releaseNeuronal activityIntragastric glucoseNeuronal responsesSuccessful weight lossHealthy body weightSignificant weight lossBrain responsesPathological feeding behaviorsWeight regainHunger scoresLipid infusionLean participantsCaloric intakePlasma hormonesObesityBody weightInfusionNutrient signalsHigh rateMedial Nucleus Accumbens Projections to the Ventral Tegmental Area Control Food Consumption
Bond CW, Trinko R, Foscue E, Furman K, Groman SM, Taylor JR, DiLeone RJ. Medial Nucleus Accumbens Projections to the Ventral Tegmental Area Control Food Consumption. Journal Of Neuroscience 2020, 40: 4727-4738. PMID: 32354856, PMCID: PMC7294796, DOI: 10.1523/jneurosci.3054-18.2020.Peer-Reviewed Original ResearchConceptsControl food intakeNAc projectionsFood intakeAccumbens projectionsLateral hypothalamusMesolimbic circuitsFood consumptionNucleus accumbens projectionsFood-seeking behaviorNAC controlVTA pathwayInhibitory projectionsMale miceNAc shellOptogenetic activationFiber photometryOptogenetic inhibitionPermissive rolePharmacological studiesDrug rewardVTAConsummatory behaviorIntakeAdaptive inhibitionNeural activityMedial prefrontal D1 dopamine neurons control food intake
Land BB, Narayanan NS, Liu RJ, Gianessi CA, Brayton CE, M Grimaldi D, Sarhan M, Guarnieri DJ, Deisseroth K, Aghajanian GK, DiLeone RJ. Medial prefrontal D1 dopamine neurons control food intake. Nature Neuroscience 2014, 17: 248-253. PMID: 24441680, PMCID: PMC3968853, DOI: 10.1038/nn.3625.Peer-Reviewed Original ResearchMeSH KeywordsAmygdalaAnalysis of VarianceAnimalsBiophysicsCalcium-Calmodulin-Dependent Protein Kinase Type 2ChannelrhodopsinsEatingElectric StimulationFemaleFood DeprivationFunctional LateralityGene Expression RegulationIn Vitro TechniquesLuminescent ProteinsMaleMembrane PotentialsMiceMice, Inbred C57BLMice, TransgenicNeural InhibitionNeural PathwaysNeuronsOptogeneticsPatch-Clamp TechniquesPhotic StimulationPrefrontal CortexReceptors, Dopamine D1Time Factors
2024
The endogenous opioid system in the medial prefrontal cortex mediates ketamine’s antidepressant-like actions
Jiang C, DiLeone R, Pittenger C, Duman R. The endogenous opioid system in the medial prefrontal cortex mediates ketamine’s antidepressant-like actions. Translational Psychiatry 2024, 14: 90. PMID: 38346984, PMCID: PMC10861497, DOI: 10.1038/s41398-024-02796-0.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexAction of ketamineEndogenous opioid systemAntidepressant-like actionOpioid systemB-endorphinKetamine treatmentAntidepressant-like actions of ketamineBehavioral actions of ketamineAntidepressant actions of ketamineBehavioral effects of ketamineSingle dose of ketamineAntidepressant-like effectsLevels of B-endorphinAcute systemic administrationEffects of ketamineDose of ketamineOpioid receptor antagonistAntidepressant actionPrefrontal cortexActivation of opioid receptorsBehavioral effectsBehavioral actionsCompetitive opioid receptor antagonistOpioid receptors
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
2019
Orbitofrontal Circuits Control Multiple Reinforcement-Learning Processes
Groman SM, Keistler C, Keip AJ, Hammarlund E, DiLeone RJ, Pittenger C, Lee D, Taylor JR. Orbitofrontal Circuits Control Multiple Reinforcement-Learning Processes. Neuron 2019, 103: 734-746.e3. PMID: 31253468, PMCID: PMC6893860, DOI: 10.1016/j.neuron.2019.05.042.Peer-Reviewed Original ResearchOptogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects
Hare BD, Shinohara R, Liu RJ, Pothula S, DiLeone RJ, Duman RS. Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects. Nature Communications 2019, 10: 223. PMID: 30644390, PMCID: PMC6333924, DOI: 10.1038/s41467-018-08168-9.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexAntidepressant effectsPyramidal cellsNovel rapid-acting antidepressantsRapid antidepressant effectsRapid-acting antidepressantsRapid antidepressant responseRapid antidepressant actionsAntidepressant actionAntidepressant responsePyramidal neuronsTherapeutic responseDRD2 dopamine receptorAnxiolytic responseDopamine receptorsSomatic stimulationTarget neuronsImpaired functionMajor subtypesOptogenetic stimulationParticular subtypeDownstream circuitryPrefrontal cortexKetamineNeurons
2018
Striatal dopamine regulates systemic glucose metabolism in humans and mice
Ter Horst KW, Lammers NM, Trinko R, Opland DM, Figee M, Ackermans MT, Booij J, van den Munckhof P, Schuurman PR, Fliers E, Denys D, DiLeone RJ, la Fleur SE, Serlie MJ. Striatal dopamine regulates systemic glucose metabolism in humans and mice. Science Translational Medicine 2018, 10 PMID: 29794060, DOI: 10.1126/scitranslmed.aar3752.Peer-Reviewed Original ResearchConceptsSystemic glucose metabolismDeep brain stimulationPeripheral insulin sensitivityGlucose metabolismInsulin sensitivityStriatal dopamineBilateral deep brain stimulationStriatal neuronal activityPeripheral glucose metabolismReceptor-expressing neuronsStriatal dopamine signalingObservational human studiesNondiabetic patientsInsulin requirementsDopamine depletionGlucose toleranceObsessive-compulsive disorderDiabetes patientsInternal capsuleStriatal areasDopamine releaseHealthy subjectsAnterior limbNucleus accumbensNeuronal activity
2016
Innate Fear-Induced Weight Regulation in the C57BL/6J Mouse
Genné-Bacon EA, Trinko JR, DiLeone RJ. Innate Fear-Induced Weight Regulation in the C57BL/6J Mouse. Frontiers In Behavioral Neuroscience 2016, 10: 132. PMID: 27458352, PMCID: PMC4930939, DOI: 10.3389/fnbeh.2016.00132.Peer-Reviewed Original ResearchHigh-fat dietWeight regulationBody weightBrown adipose thermogenesisDifferential weight gainWeek old miceLong-term neural plasticityDorsomedial hypothalamusFat dietAdipose thermogenesisC57BL/6J miceDiet groupFood intakeBA groupNeural plasticityChronic stressWeight gainAversive doseMiceΔFosB proteinButyric acidMT exposureActivity levelsUnderlying mechanismMetabolic adaptationThe vitamin D metabolites 25(OH)D and 1,25(OH)2D are not related to either glucose metabolism or insulin action in obese women
Horst K, Versteeg RI, Gilijamse PW, Ackermans MT, Heijboer AC, Romijn JA, la Fleur SE, Trinko R, DiLeone RJ, Serlie MJ. The vitamin D metabolites 25(OH)D and 1,25(OH)2D are not related to either glucose metabolism or insulin action in obese women. Diabetes & Metabolism 2016, 42: 416-423. PMID: 27262368, DOI: 10.1016/j.diabet.2016.04.011.Peer-Reviewed Original ResearchConceptsVitamin D deficiencyObese womenInsulin actionD deficiencyVitamin DInsulin resistanceInsulin sensitivityGlucose metabolismEuglycaemic–hyperinsulinaemic clamp studiesActive vitamin D metaboliteBasal endogenous glucose productionObesity-related insulin resistanceTissue-specific insulin actionObesity-induced metabolic diseasesTissue-specific insulin sensitivitySkeletal muscle insulin sensitivityBody mass indexVitamin D metabolitesTotal body fatMuscle insulin sensitivityEndogenous glucose productionBaseline characteristicsSerum levelsMass indexD levelsActivity of D1/2 Receptor Expressing Neurons in the Nucleus Accumbens Regulates Running, Locomotion, and Food Intake
Zhu X, Ottenheimer D, DiLeone RJ. Activity of D1/2 Receptor Expressing Neurons in the Nucleus Accumbens Regulates Running, Locomotion, and Food Intake. Frontiers In Behavioral Neuroscience 2016, 10: 66. PMID: 27147989, PMCID: PMC4828436, DOI: 10.3389/fnbeh.2016.00066.Peer-Reviewed Original ResearchD2 neuronsFood intakeEnergy intakeExcessive energy intakeNeuronal manipulationInhibition of D1Expressing NeuronsD2 receptorsDesigner receptorsD1 neuronsNucleus accumbensDopamine pathwayNeuron inhibitionWeight controlLocomotor activityBrain regionsDrug strategiesWeight gainBehavioral effectsNeuronsIntakeWheel runningEnergy expenditureReward behaviorNeural activity
2015
Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions
Fuchikami M, Thomas A, Liu R, Wohleb ES, Land BB, DiLeone RJ, Aghajanian GK, Duman RS. Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 8106-8111. PMID: 26056286, PMCID: PMC4491758, DOI: 10.1073/pnas.1414728112.Peer-Reviewed Original ResearchConceptsIL-PFCOptogenetic stimulationAntidepressant actionAnxiolytic effectsSystemic ketamineLayer V pyramidal neuronsSystemic ketamine administrationInfralimbic prefrontal cortexPrecise cellular mechanismsKetamine infusionKetamine administrationPyramidal neuronsAnxiolytic actionDepressed patientsSpine synapsesSynaptic responsesNeuronal inactivationRodent modelsNeuronal activityKetaminePrefrontal cortexBehavioral actionsCellular mechanismsStimulationPatientsTargeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome
Xu M, Kobets A, Du JC, Lennington J, Li L, Banasr M, Duman RS, Vaccarino FM, DiLeone RJ, Pittenger C. Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 893-898. PMID: 25561540, PMCID: PMC4311862, DOI: 10.1073/pnas.1419533112.Peer-Reviewed Original ResearchConceptsTourette syndromeCholinergic interneuronsDorsolateral striatumSensorimotor gatingD-amphetamine challengeLarge cholinergic interneuronsSpecific cell ablationInterneuron deficitsStriatal interneuronsAcute administrationGABAergic markersDopaminergic drugsAvailable treatmentsPostmortem studiesPrepulse inhibitionTic disordersSevere diseaseHuman putamenMotor coordinationInterneuronsTargeted ablationSevere endStriatumAcute stressGilles de
2014
Optogenetic inhibition of neurons by internal light production
Land BB, Brayton CE, Furman KE, LaPalombara Z, DiLeone RJ. Optogenetic inhibition of neurons by internal light production. Frontiers In Behavioral Neuroscience 2014, 8: 108. PMID: 24744708, PMCID: PMC3978322, DOI: 10.3389/fnbeh.2014.00108.Peer-Reviewed Original ResearchOptogenetic inhibitionAmphetamine-induced locomotor activityNeural activityLuciferase-expressing virusesSuppress neural activitySpecific molecular pathwaysAdeno-associated virusLuciferase miceNeuronal activityLocomotor activityNeural circuitsActivation/inhibitionAdministrationMolecular pathwaysFos activityDelivery of lightVivo optogeneticsInhibitionMiceAnimalsVirusLuciferaseOptogeneticsOptical fiberStriatum
2012
Prefrontal D1 dopamine signaling is required for temporal control
Narayanan NS, Land BB, Solder JE, Deisseroth K, DiLeone RJ. Prefrontal D1 dopamine signaling is required for temporal control. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 20726-20731. PMID: 23185016, PMCID: PMC3528521, DOI: 10.1073/pnas.1211258109.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBehavior, AnimalBiological ClocksMaleMiceMice, TransgenicModels, NeurologicalNeural PathwaysOptogeneticsPrefrontal CortexRatsReceptors, Dopamine D1RewardRNA InterferenceRNA, Small InterferingSignal TransductionSynaptic TransmissionTime FactorsTyrosine 3-MonooxygenaseVentral Tegmental AreaConceptsVentral tegmental areaD1 dopamine receptorsDopamine receptorsTegmental areaDopaminergic projectionsPrefrontal neuronsMidbrain ventral tegmental areaD2 dopamine receptorsDopaminergic inputD1 receptorsDopaminergic neurotransmissionD1 dopamineDopaminergic diseasesTyrosine hydroxylaseDopamine signalingReceptorsPharmacological disruptionSelective inhibitionGoal-directed behaviorNeuronsRNA interferenceTiming taskBehavioral goalsControlNeurotransmissionGene Profiling Reveals a Role for Stress Hormones in the Molecular and Behavioral Response to Food Restriction
Guarnieri DJ, Brayton CE, Richards SM, Maldonado-Aviles J, Trinko JR, Nelson J, Taylor JR, Gourley SL, DiLeone RJ. Gene Profiling Reveals a Role for Stress Hormones in the Molecular and Behavioral Response to Food Restriction. Biological Psychiatry 2012, 71: 358-365. PMID: 21855858, PMCID: PMC3237832, DOI: 10.1016/j.biopsych.2011.06.028.Peer-Reviewed Original ResearchConceptsFood restrictionGene expressionExpression changesStress-responsive genesBrain regionsWhole-genome microarraysPersistent expression changesGene expression profilesMale C57BL/6J miceAdministration of corticosteroneVentral tegmental areaIntact adrenal glandsEnzyme-linked immunosorbentMedial prefrontal cortexQuantitative polymerase chain reactionResponsive genesNonrestricted animalsDaily injectionsAdrenal glandC57BL/6J miceExpression profilesPlasma levelsPolymerase chain reactionCORT treatmentTegmental area