2021
Drp1 is required for AgRP neuronal activity and feeding
Jin S, Yoon NA, Liu ZW, Song JE, Horvath TL, Kim JD, Diano S. Drp1 is required for AgRP neuronal activity and feeding. ELife 2021, 10: e64351. PMID: 33689681, PMCID: PMC7946429, DOI: 10.7554/elife.64351.Peer-Reviewed Original ResearchConceptsAgRP neuronal activityFatty acid oxidationAgRP neuronsNeuronal activityAgRP neuronal functionHypothalamic AgRP neuronsBody weight regulationMitochondrial fatty acid utilizationWhole-body energy homeostasisHypothalamic orexigenic agoutiFatty acid utilizationAcid oxidationFat massCKO miceNeuronal activationPeptide-1Body weightNeuronal functionOrexigenic agoutiEnergy homeostasisMitochondrial fissionSignificant decreaseEnergy expenditureNeuronsAcid utilization
2020
Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice
Tan Y, Hang F, Liu ZW, Stoiljkovic M, Wu M, Tu Y, Han W, Lee AM, Kelley C, Hajos M, Lu L, de Lecea L, de Araujo I, Picciotto M, Horvath TL, Gao XB. Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice. Journal Of Clinical Investigation 2020, 130: 4985-4998. PMID: 32516139, PMCID: PMC7456212, DOI: 10.1172/jci130889.Peer-Reviewed Original ResearchConceptsHcrt cellsObese miceDiet-induced obese miceObese male miceExcessive energy intakeNeuropeptide hypocretin/orexinHypocretin/orexinHcrt neuronsMale miceHcrt systemClinical studiesCommon causeSynaptic transmissionObese animalsEnergy intakeAcute stressCognitive functionSalient stimuliAlters responsesExact mechanismMiceHomeostatic regulationNeuronal networksBehavioral changesNeurons
2018
The 7q11.23 Protein DNAJC30 Interacts with ATP Synthase and Links Mitochondria to Brain Development
Tebbenkamp ATN, Varela L, Choi J, Paredes MI, Giani AM, Song JE, Sestan-Pesa M, Franjic D, Sousa AMM, Liu ZW, Li M, Bichsel C, Koch M, Szigeti-Buck K, Liu F, Li Z, Kawasawa YI, Paspalas CD, Mineur YS, Prontera P, Merla G, Picciotto MR, Arnsten AFT, Horvath TL, Sestan N. The 7q11.23 Protein DNAJC30 Interacts with ATP Synthase and Links Mitochondria to Brain Development. Cell 2018, 175: 1088-1104.e23. PMID: 30318146, PMCID: PMC6459420, DOI: 10.1016/j.cell.2018.09.014.Peer-Reviewed Original ResearchConceptsCopy number variationsATP synthase dimersOxidative phosphorylation supercomplexesHuman neurodevelopmental disordersATP synthaseWS pathogenesisGene contributionMitochondrial featuresBrain developmentWilliams syndromeMitochondrial dysfunctionNeocortical pyramidal neuronsNeural phenotypesMitochondriaPyramidal neuronsMachineryMorphological featuresNeurodevelopmental disordersDysfunctionSupercomplexesPhenotypeA Neural Circuit for Gut-Induced Reward
Han W, Tellez LA, Perkins MH, Perez IO, Qu T, Ferreira J, Ferreira TL, Quinn D, Liu ZW, Gao XB, Kaelberer MM, Bohórquez DV, Shammah-Lagnado SJ, de Lartigue G, de Araujo IE. A Neural Circuit for Gut-Induced Reward. Cell 2018, 175: 665-678.e23. PMID: 30245012, PMCID: PMC6195474, DOI: 10.1016/j.cell.2018.08.049.Peer-Reviewed Original ResearchConceptsSubstantia nigraVagal sensory gangliaVagal sensory neuronsTransneuronal labelingTransneuronal tracingVagal originBrain axisGlutamatergic neuronsSelf-stimulation behaviorParabrachial regionSensory gangliaDopamine cellsObligatory relayDopamine releaseSensory neuronsRewarding effectsNeuronal circuitryPlace preferenceReward pathwayNeural circuitsNeuronsStimulation approachesReward neuronsMajor regulatorNigra
2014
O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat
Ruan HB, Dietrich MO, Liu ZW, Zimmer MR, Li MD, Singh JP, Zhang K, Yin R, Wu J, Horvath TL, Yang X. O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat. Cell 2014, 159: 306-317. PMID: 25303527, PMCID: PMC4509746, DOI: 10.1016/j.cell.2014.09.010.Peer-Reviewed Original ResearchConceptsAgRP neuronsFundamental cellular processesWhite fatN-acetylglucosamine (O-GlcNAc) modificationOrexigenic AgRP neuronsVoltage-dependent potassium channelsCellular processesGlcNAc transferaseDynamic physiological processesNuclear proteinsWhite adipose tissue browningPhysiological processesAdipose tissue browningDiet-induced obesityPhysiological relevanceTissue browningGenetic ablationBeige cellsEnergy metabolismInsulin resistanceNeuronal excitabilityPotassium channelsAdipose tissueCentral mechanismsNeuronsLeptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding
Kim JG, Suyama S, Koch M, Jin S, Argente-Arizon P, Argente J, Liu ZW, Zimmer MR, Jeong JK, Szigeti-Buck K, Gao Y, Garcia-Caceres C, Yi CX, Salmaso N, Vaccarino FM, Chowen J, Diano S, Dietrich MO, Tschöp MH, Horvath TL. Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding. Nature Neuroscience 2014, 17: 908-910. PMID: 24880214, PMCID: PMC4113214, DOI: 10.1038/nn.3725.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesCell CountEatingExcitatory Postsynaptic PotentialsGlial Fibrillary Acidic ProteinHypothalamusImmunohistochemistryIn Situ HybridizationLeptinMaleMelanocortinsMiceMice, KnockoutMicroscopy, ElectronNerve NetNeuronsPrimary Cell CulturePro-OpiomelanocortinPulmonary Gas ExchangeReal-Time Polymerase Chain ReactionRNA, MessengerSignal Transduction
2013
Mitochondrial Dynamics Controlled by Mitofusins Regulate Agrp Neuronal Activity and Diet-Induced Obesity
Dietrich MO, Liu ZW, Horvath TL. Mitochondrial Dynamics Controlled by Mitofusins Regulate Agrp Neuronal Activity and Diet-Induced Obesity. Cell 2013, 155: 188-199. PMID: 24074868, PMCID: PMC4142434, DOI: 10.1016/j.cell.2013.09.004.Peer-Reviewed Original ResearchConceptsMitochondrial dynamicsEnergy metabolismCell-type specificCellular energy metabolismWhole-body energy metabolismKey organellesMitofusin 1Mitofusin 2High-fat dietMitochondria sizeAgRP neuronsMfn1Anorexigenic pro-opiomelanocortin (POMC) neuronsAgRP neuronal activityKnockout miceMetabolismPro-opiomelanocortin (POMC) neuronsFusion mechanismDiet-Induced ObesityMitofusinsOverfed stateImportant roleCellsDynamic changesOrganelles
2012
Prolyl Endopeptidase-Deficient Mice Have Reduced Synaptic Spine Density in the CA1 Region of the Hippocampus, Impaired LTP, and Spatial Learning and Memory
D'Agostino G, Kim JD, Liu ZW, Jeong JK, Suyama S, Calignano A, Gao XB, Schwartz M, Diano S. Prolyl Endopeptidase-Deficient Mice Have Reduced Synaptic Spine Density in the CA1 Region of the Hippocampus, Impaired LTP, and Spatial Learning and Memory. Cerebral Cortex 2012, 23: 2007-2014. PMID: 22767632, PMCID: PMC3841400, DOI: 10.1093/cercor/bhs199.Peer-Reviewed Original ResearchConceptsSynaptic spine densitySpine densityCA1 regionProlyl endopeptidaseHippocampal long-term potentiationLong-term potentiationHippocampal-mediated learningImpaired LTPWild-type controlsSpatial memory formationHippocampal plasticityCognitive impairmentPharmacological manipulationNeurodegenerative disordersSpatial learningMemory formationHippocampusPossible roleMicePhysiological functionsSerine proteasesBehavioral approachPotentiationDiseaseNeuropeptides
2010
Direct Evidence for Wake-Related Increases and Sleep-Related Decreases in Synaptic Strength in Rodent Cortex
Liu ZW, Faraguna U, Cirelli C, Tononi G, Gao XB. Direct Evidence for Wake-Related Increases and Sleep-Related Decreases in Synaptic Strength in Rodent Cortex. Journal Of Neuroscience 2010, 30: 8671-8675. PMID: 20573912, PMCID: PMC2903226, DOI: 10.1523/jneurosci.1409-10.2010.Peer-Reviewed Original ResearchConceptsMiniature EPSCsAmplitude of mEPSCsFrontal cortex slicesNet synaptic potentiationCerebral cortexCortex slicesLarge brain areasSynaptic potentiationSynaptic currentsBrain areasRodent cortexStrong synapsesRecovery sleepSynaptic homeostasisSynaptic strengthSleepCortexSynapsesEPSCsTime of dayRatsPotentiationMiceDirect evidence
2009
Prolylcarboxypeptidase regulates food intake by inactivating α-MSH in rodents
Wallingford N, Perroud B, Gao Q, Coppola A, Gyengesi E, Liu ZW, Gao XB, Diament A, Haus KA, Shariat-Madar Z, Mahdi F, Wardlaw SL, Schmaier AH, Warden CH, Diano S. Prolylcarboxypeptidase regulates food intake by inactivating α-MSH in rodents. Journal Of Clinical Investigation 2009, 119: 2291-2303. PMID: 19620781, PMCID: PMC2719925, DOI: 10.1172/jci37209.Peer-Reviewed Original ResearchConceptsFood intakeHigh-fat diet-induced obesityReduced body fatRegular chow dietDiet-induced obesityPRCP activityWild-type controlsChow dietMelanocortin signalingObese miceWeight maintenanceReal-time PCRAxon terminalsBody fatNeuronal populationsΑ-MSHBrain tissueMRNA expressionMouse strainsSmall molecule protease inhibitorsElevated levelsVivo activityProlylcarboxypeptidaseProtease inhibitorsHypothalamus
2007
Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons
Rao Y, Liu ZW, Borok E, Rabenstein RL, Shanabrough M, Lu M, Picciotto MR, Horvath TL, Gao XB. Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons. Journal Of Clinical Investigation 2007, 117: 4022-4033. PMID: 18060037, PMCID: PMC2104495, DOI: 10.1172/jci32829.Peer-Reviewed Original ResearchConceptsHypocretin/orexin neuronsLong-term potentiationOrexin neuronsGlutamatergic synapsesSynaptic plasticitySleep lossExperience-dependent synaptic plasticityDopamine D1 receptorsChronic sleep lossSleep-wake regulationModafinil treatmentLateral hypothalamusD1 receptorsSimilar potentiationBrain slicesNeuronal activityNeuronal circuitryDopamine systemNervous systemSynaptic strengthNeuronsPathological conditionsGentle handlingMiceWakefulness
2006
Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite
Abizaid A, Liu ZW, Andrews ZB, Shanabrough M, Borok E, Elsworth JD, Roth RH, Sleeman MW, Picciotto MR, Tschöp MH, Gao XB, Horvath TL. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. Journal Of Clinical Investigation 2006, 116: 3229-3239. PMID: 17060947, PMCID: PMC1618869, DOI: 10.1172/jci29867.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAppetiteDopamineFluorescent Antibody TechniqueGhrelinMaleMesencephalonMiceMice, Inbred C57BLMice, KnockoutNeuronsNucleus AccumbensPatch-Clamp TechniquesPeptide HormonesRatsRats, Sprague-DawleyReceptors, GhrelinReceptors, G-Protein-CoupledTime FactorsVentral Tegmental AreaConceptsVentral tegmental areaGHSR-deficient miceGHSR-dependent mannerGut hormone ghrelinDopamine neuronal activityMidbrain dopamine neuronsMesolimbic reward circuitrySynaptic input organizationPeripheral ghrelinRebound feedingVTA administrationOrexigenic effectDopamine turnoverGHSR antagonistDopamine neuronsHypothalamic centersTegmental areaHormone ghrelinNucleus accumbensGhrelinNeuronal activitySynapse formationReward circuitryInput organizationFeeding schedule