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
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
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 mechanismsStimulationPatients
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