2023
A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model
Lv H, Catarino J, Li D, Liu B, Gao X, Horvath T, Huang Y. A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2300015120. PMID: 37036983, PMCID: PMC10120042, DOI: 10.1073/pnas.2300015120.Peer-Reviewed Original ResearchConceptsVesicular GABA transporterActivity-based anorexiaExpression of AgRPNeuropeptide YAgRP neuronsAnorexia nervosaAnxiety/depressive-like behaviorsHypothalamic AgRP neuronsDepressive-like behaviorCurrent treatment optionsHigh relapse rateStress-related disordersHuman neuronal cellsNutritional supportRelapse rateTreatment optionsAnxiolytic effectsPsychiatric illnessMouse modelAnimal modelsHigh mortalityGABA transporterGenetic ablationNeuronal cellsNeurons
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
2019
A step towards the automation of intracytoplasmic sperm injection: real time confirmation of mouse and human oocyte penetration and viability by electrical resistance measurement
Mor A, Zhang M, Esencan E, Simsek B, Nichols-Burns SM, Liu Y, Lo J, Kelk DA, Flores V, Gao XB, Seli E. A step towards the automation of intracytoplasmic sperm injection: real time confirmation of mouse and human oocyte penetration and viability by electrical resistance measurement. Fertility And Sterility 2019, 113: 234-236. PMID: 31883732, DOI: 10.1016/j.fertnstert.2019.09.023.Peer-Reviewed Original ResearchConceptsIntracytoplasmic sperm injectionICSI pipetteSperm injectionOocyte penetrationIntact oolemmaOocyte retrieval procedureMann-Whitney testMouse oocytesOocyte retrievalFemale miceMAIN OUTCOMEAcademic centersImmature oocytesHuman oocytesMature oocytesObjective toolMiceOocytesWomenVisual assessmentPipetteInjectionOolemmaStep 1Group
2013
Repeated in vivo exposure of cocaine induces long‐lasting synaptic plasticity in hypocretin/orexin‐producing neurons in the lateral hypothalamus in mice
Rao Y, Mineur YS, Gan G, Wang AH, Liu Z, Wu X, Suyama S, de Lecea L, Horvath TL, Picciotto MR, Gao X. Repeated in vivo exposure of cocaine induces long‐lasting synaptic plasticity in hypocretin/orexin‐producing neurons in the lateral hypothalamus in mice. The Journal Of Physiology 2013, 591: 1951-1966. PMID: 23318871, PMCID: PMC3624862, DOI: 10.1113/jphysiol.2012.246983.Peer-Reviewed Original ResearchConceptsCAMP response element-binding proteinHypocretin neuronsLong-term potentiationSynaptic potentiationLateral hypothalamusCocaine administrationExperience-dependent synaptic potentiationExperience-dependent potentiationHypocretin-producing neuronsVivo cocaine administrationCocaine-treated animalsOrexin-producing neuronsAMPA-type glutamate receptorsVentral tegmental areaHigh-frequency stimulationCocaine-treated micePlace preference protocolResponse element-binding proteinDrugs of abuseCocaine withdrawalTegmental areaGlutamatergic synapsesGlutamate receptorsHypocretin systemElement-binding protein
2011
Intracellular energy status regulates activity in hypocretin/orexin neurones: a link between energy and behavioural states
Liu Z, Gan G, Suyama S, Gao X. Intracellular energy status regulates activity in hypocretin/orexin neurones: a link between energy and behavioural states. The Journal Of Physiology 2011, 589: 4157-4166. PMID: 21727218, PMCID: PMC3180576, DOI: 10.1113/jphysiol.2011.212514.Peer-Reviewed Original ResearchEndometrial stem cell transplantation restores dopamine production in a Parkinson’s disease model
Wolff EF, Gao X, Yao KV, Andrews ZB, Du H, Elsworth JD, Taylor HS. Endometrial stem cell transplantation restores dopamine production in a Parkinson’s disease model. Journal Of Cellular And Molecular Medicine 2011, 15: 747-755. PMID: 20406327, PMCID: PMC2998585, DOI: 10.1111/j.1582-4934.2010.01068.x.Peer-Reviewed Original ResearchConceptsParkinson's diseaseDopaminergic neuronsWhole-cell patch-clamp recordingsCell patch-clamp recordingsDopamine metabolite concentrationsPD mouse modelStem cell transplantationDisease modelsSite of lesionParkinson's disease modelPyramidal cell bodiesPatch-clamp recordingsMesenchymal stem-like cellsAllogenic stem cellsStem cellsStem-like cellsCell transplantationStriatal dopamineNeural markers nestinCentral neuronsDopaminergic cellsDendritic projectionsDopamine synthesisDopamine productionMouse model
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 evidenceExperience‐dependent plasticity in hypocretin/orexin neurones: re‐setting arousal threshold
Gao X, Wang AH. Experience‐dependent plasticity in hypocretin/orexin neurones: re‐setting arousal threshold. Acta Physiologica 2010, 198: 251-262. PMID: 19785627, PMCID: PMC2860674, DOI: 10.1111/j.1748-1716.2009.02047.x.Peer-Reviewed Original ResearchConceptsExperience-dependent plasticityExperience-dependent changesEnvironmental cuesArousal levelMaintenance of arousalBrain areasAddictive drugsBrain functionSynaptic architectureLateral hypothalamusAnimal behaviorExtensive innervationNeuropeptide hypocretinArousal thresholdCore processesSynaptic plasticityHypocretin/orexin neuronesArousalAnimal survivalEnvironmental factorsPlasticityBehavioral factorsNeuronesBehavioral changesOrexin neurones
2008
Regulation of Synaptic Efficacy in Hypocretin/Orexin-Containing Neurons by Melanin Concentrating Hormone in the Lateral Hypothalamus
Rao Y, Lu M, Ge F, Marsh DJ, Qian S, Wang AH, Picciotto MR, Gao XB. Regulation of Synaptic Efficacy in Hypocretin/Orexin-Containing Neurons by Melanin Concentrating Hormone in the Lateral Hypothalamus. Journal Of Neuroscience 2008, 28: 9101-9110. PMID: 18784290, PMCID: PMC2562258, DOI: 10.1523/jneurosci.1766-08.2008.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnalysis of VarianceAnimalsAnimals, NewbornBehavior, AnimalBenzazepinesBenzhydryl CompoundsCentral Nervous System StimulantsDopamine AgonistsDose-Response Relationship, DrugExcitatory Amino Acid AgentsGlutamic AcidGreen Fluorescent ProteinsHypothalamic Area, LateralHypothalamic HormonesIn Vitro TechniquesIntracellular Signaling Peptides and ProteinsMelaninsMiceMice, Inbred C57BLMice, TransgenicModafinilMotor ActivityNeuronsNeuropeptidesOrexinsPertussis ToxinPituitary HormonesReceptors, SomatostatinSynapsesSynaptic TransmissionTime FactorsConceptsHypocretin/orexin neuronsMCHR1 KO miceOrexin-containing neuronsLateral hypothalamusWild-type miceOrexin neuronsHypocretin/orexinKO miceMCH receptor 1Action potential firingEffects of modafinilMelanin-Concentrating HormoneHypocretin/orexin signalingGroups of neuronsMCH neuronsMiniature EPSCsWT miceHypocretin/Glutamatergic synapsesOrexin signalingSynaptic transmissionPertussis toxinBrain areasReciprocal innervationInhibitory influence
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
Adenosine Inhibits Activity of Hypocretin/Orexin Neurons by the A1 Receptor in the Lateral Hypothalamus: A Possible Sleep-Promoting Effect
Liu ZW, Gao XB. Adenosine Inhibits Activity of Hypocretin/Orexin Neurons by the A1 Receptor in the Lateral Hypothalamus: A Possible Sleep-Promoting Effect. Journal Of Neurophysiology 2006, 97: 837-848. PMID: 17093123, PMCID: PMC1783688, DOI: 10.1152/jn.00873.2006.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAdenosineAdenosine A1 Receptor AgonistsAnimalsArousalCalcium ChannelsDose-Response Relationship, DrugExcitatory Postsynaptic PotentialsGreen Fluorescent ProteinsHypothalamic Area, LateralImmunohistochemistryIntracellular Signaling Peptides and ProteinsMiceMice, TransgenicNeural InhibitionNeuronsNeuropeptidesOrexinsOrgan Culture TechniquesPertussis ToxinReceptor, Adenosine A1SleepSynaptic TransmissionConceptsHypocretin/orexin neuronsOrexin neuronsSleep-promoting effectsLateral hypothalamusBasal forebrainA1 receptorsMiniature excitatory postsynaptic currentsVoltage-dependent calcium currentsAdenosine-mediated inhibitionHypocretin/orexin systemExcitatory postsynaptic potentialsExcitatory synaptic transmissionExcitatory postsynaptic currentsEffects of adenosineHypocretin/orexinPostsynaptic currentsOrexin systemPostsynaptic potentialsCalcium currentSynaptic transmissionBrain slicesPertussis toxinSleep promoterAdenosine receptorsAction potentials
2005
Input organization and plasticity of hypocretin neurons Possible clues to obesity’s association with insomnia
Horvath TL, Gao XB. Input organization and plasticity of hypocretin neurons Possible clues to obesity’s association with insomnia. Cell Metabolism 2005, 1: 279-286. PMID: 16054072, DOI: 10.1016/j.cmet.2005.03.003.Peer-Reviewed Original ResearchConceptsHypocretin neuronsSynaptic currentsHypothalamic hypocretin neuronsMore excitatory synapsesOvernight food deprivationElevated food intakeExcitatory synaptic currentsControl of arousalCause of narcolepsyStress-induced plasticityHypocretin levelsLeptin administrationHypocretin cellsHypocretin signalingMetabolic disturbancesObesity associationSynaptic organizationExcitatory synapsesFood intakeInhibitory inputsCell bodiesUnderlying causeNeuronsInput organizationFood deprivation
2002
Hypocretin/Orexin Excites Hypocretin Neurons via a Local Glutamate Neuron—A Potential Mechanism for Orchestrating the Hypothalamic Arousal System
Li Y, Gao X, Sakurai T, van den Pol AN. Hypocretin/Orexin Excites Hypocretin Neurons via a Local Glutamate Neuron—A Potential Mechanism for Orchestrating the Hypothalamic Arousal System. Neuron 2002, 36: 1169-1181. PMID: 12495630, DOI: 10.1016/s0896-6273(02)01132-7.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsArousalCarrier ProteinsExcitatory Amino Acid AgonistsFeedbackGABA AgonistsGamma-Aminobutyric AcidGenes, ReporterGlutamic AcidGreen Fluorescent ProteinsHypothalamusImmunohistochemistryIntracellular Signaling Peptides and ProteinsLuminescent ProteinsMiceMice, TransgenicNeural InhibitionNeural PathwaysNeuronsNeuropeptidesOrexinsPresynaptic TerminalsSodium Channel BlockersSynaptic TransmissionConceptsHypothalamic arousal systemsHypocretin neuronsArousal systemSpike frequencyLocal glutamatergic neuronsMouse brain slicesGlutamate releaseGlutamatergic neuronsHypocretin-1Hypocretin cellsPresynaptic facilitationBrain slicesNeuron activityOutward currentsEnergy homeostasisModulates sleepNeuronsPotential mechanismsDirect effectPossible mechanismCellsNarcolepsyHypocretinNorepinephrineAcetylcholineMelanin‐concentrating hormone depresses L‐, N‐, and P/Q‐type voltage‐dependent calcium channels in rat lateral hypothalamic neurons
Gao X, van den Pol A. Melanin‐concentrating hormone depresses L‐, N‐, and P/Q‐type voltage‐dependent calcium channels in rat lateral hypothalamic neurons. The Journal Of Physiology 2002, 542: 273-286. PMID: 12096069, PMCID: PMC2290404, DOI: 10.1113/jphysiol.2002.019372.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium Channel BlockersCalcium Channels, L-TypeCalcium Channels, N-TypeCalcium Channels, P-TypeCells, CulturedFemaleGTP-Binding ProteinsHypothalamic HormonesHypothalamusImage Processing, Computer-AssistedIn Vitro TechniquesMelaninsMembrane PotentialsNeuronsPatch-Clamp TechniquesPituitary HormonesPregnancyRatsRats, Sprague-DawleySignal TransductionConceptsMelanin-concentrating hormoneLH neuronsCalcium currentNon-neuronal cellsHighest MCh concentrationMCH concentrationPertussis toxinCalcium channelsActions of MCHPTX-sensitive G protein pathwayRat lateral hypothalamic neuronsQ-type voltage-dependent calcium channelsVoltage-dependent calcium currentsQ-type calcium channelsVoltage-dependent calcium channelsInhibitory effectLateral hypothalamic neuronsLateral hypothalamic areaN-type currentWhole-cell recordingsVoltage-activated currentsG proteinsN-type channelsExcitatory actionHypothalamic areaHypocretin (orexin) enhances neuron activity and cell synchrony in developing mouse GFP‐expressing locus coeruleus
van den Pol A, Ghosh PK, Liu R, Li Y, Aghajanian GK, Gao X. Hypocretin (orexin) enhances neuron activity and cell synchrony in developing mouse GFP‐expressing locus coeruleus. The Journal Of Physiology 2002, 541: 169-185. PMID: 12015428, PMCID: PMC2290314, DOI: 10.1113/jphysiol.2002.017426.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCells, CulturedDose-Response Relationship, DrugElectrophysiologyFemaleGreen Fluorescent ProteinsImmunohistochemistryIn Vitro TechniquesIntracellular Signaling Peptides and ProteinsLocus CoeruleusLuminescent ProteinsMembrane PotentialsMiceMice, TransgenicMicroscopy, ConfocalNeuronsNeuropeptidesNeurotransmitter AgentsOrexinsPatch-Clamp TechniquesPregnancyTyrosine 3-MonooxygenaseConceptsLocus coeruleusHypocretin-1Mouse prion promoterGlutamate receptor antagonistsPresence of TTXImmunoreactive tyrosine hydroxylaseRat locus coeruleusNeonatal mouse brainPostnatal day 0Higher brain centersNew transgenic mouseSingle-unit recordingsInward cation currentMembrane potentialDual cell recordingsImproved cognitive performanceNoradrenergic neuronsLC neuronsHypocretin neuronsImmature neuronsPrion promoterReceptor antagonistMouse slicesTyrosine hydroxylaseExcitatory mechanisms
2001
Membrane Properties Underlying Patterns of GABA-Dependent Action Potentials in Developing Mouse Hypothalamic Neurons
Wang Y, Gao X, van den Pol A. Membrane Properties Underlying Patterns of GABA-Dependent Action Potentials in Developing Mouse Hypothalamic Neurons. Journal Of Neurophysiology 2001, 86: 1252-1265. PMID: 11535674, DOI: 10.1152/jn.2001.86.3.1252.Peer-Reviewed Original ResearchConceptsHypothalamic neuronsAction potentialsMouse hypothalamusMultiple spikesSpike thresholdFrequency of GABAMediobasal hypothalamic neuronsProbability of GABAGlutamate receptor antagonistsConventional whole cellMouse hypothalamic neuronsMultiple action potentialsPostnatal day 2Intrinsic membrane propertiesMean reversal potentialIonotropic glutamate receptorsSimilar spike patternsPeaks of depolarizationGABA excitationMembrane potentialReceptor antagonistSpike patternsExcitatory activityGlutamate receptorsSynaptic transmissionMelanin concentrating hormone depresses synaptic activity of glutamate and GABA neurons from rat lateral hypothalamus
Gao X, van den Pol A. Melanin concentrating hormone depresses synaptic activity of glutamate and GABA neurons from rat lateral hypothalamus. The Journal Of Physiology 2001, 533: 237-252. PMID: 11351031, PMCID: PMC2278620, DOI: 10.1111/j.1469-7793.2001.0237b.x.Peer-Reviewed Original ResearchMeSH Keywords2-Amino-5-phosphonovalerate6-Cyano-7-nitroquinoxaline-2,3-dioneAction PotentialsAnimalsBicucullineCarrier ProteinsCells, CulturedElectric ConductivityExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsFemaleFetusGABA AntagonistsGamma-Aminobutyric AcidGlutamic AcidGTP-Binding ProteinsHypothalamic Area, LateralHypothalamic HormonesIn Vitro TechniquesIntracellular Signaling Peptides and ProteinsMelaninsNeuronsNeuropeptidesOrexin ReceptorsOrexinsPatch-Clamp TechniquesPituitary HormonesPotassiumPregnancyRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledReceptors, GlutamateReceptors, NeuropeptideSodiumSynaptic TransmissionTetrodotoxinConceptsSynaptic activityLH neuronsAction potentialsPotassium channelsActions of MCHInhibitory synaptic eventsGABAB receptor agonistAmino acid transmittersLateral hypothalamic areaCalcium-dependent releasePresence of tetrodotoxinRat lateral hypothalamusEffect of MCHFast synaptic activityGlutamate-evoked currentsWhole-cell recordingsPostsynaptic glutamate receptorsNon-neuronal cellsMiniature excitatory currentsVoltage-dependent potassium channelsNeuropeptide melaninGABA neuronsVoltage-clamp experimentsExcitatory actionLH actionLateral hypothalamus: Early developmental expression and response to hypocretin (orexin)
Van Den Pol A, Patrylo P, Ghosh P, Gao X. Lateral hypothalamus: Early developmental expression and response to hypocretin (orexin). The Journal Of Comparative Neurology 2001, 433: 349-363. PMID: 11298360, DOI: 10.1002/cne.1144.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAnimals, NewbornBrainCalciumCarrier ProteinsCells, CulturedElectrophysiologyEmbryo, MammalianHypothalamic Area, LateralImmunohistochemistryIn Vitro TechniquesIntracellular Signaling Peptides and ProteinsNeuronsNeuropeptidesOrexin ReceptorsOrexinsRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledReceptors, NeuropeptideRNA, MessengerConceptsLateral hypothalamic areaSynaptic activityLH neuronsNeuronal activitySleep regulationWhole-cell patch-clamp recordingsRobust increaseAdult central nervous systemEndocrine controlPostnatal day 1Day of birthCentral nervous systemPatch-clamp recordingsVoltage-clamp recordingsEmbryonic day 19Hypocretin-1Excitatory influenceHypothalamic areaHypocretin-2Spinal cordMature brainFood intakeHypocretin systemLH cellsReceptor mRNAGABA, Not Glutamate, a Primary Transmitter Driving Action Potentials in Developing Hypothalamic Neurons
Gao X, Van Den Pol A. GABA, Not Glutamate, a Primary Transmitter Driving Action Potentials in Developing Hypothalamic Neurons. Journal Of Neurophysiology 2001, 85: 425-434. PMID: 11152743, DOI: 10.1152/jn.2001.85.1.425.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsBicucullineCells, CulturedChloridesExcitatory Amino Acid AntagonistsGABA-A Receptor AntagonistsGamma-Aminobutyric AcidGlutamic AcidGramicidinHypothalamusImmunohistochemistryIn Vitro TechniquesMiceNeuronsNeurotransmitter AgentsPatch-Clamp TechniquesReceptors, GlutamateSpinal CordConceptsHypothalamic neuronsReceptor antagonist bicucullinePrimary inhibitory neurotransmitterMouse hypothalamic neuronsPrimary excitatory transmitterAntagonist bicucullineExcitatory transmitterGABA circuitsGlutamate transmissionInhibitory neurotransmitterMature brainBrain slicesSynaptic releaseNeuronal activitySpike activityNeuronal connectionsSpike frequencyExtracellular recordingsAction potentialsAntagonist 2Brain developmentHebbian mechanismsIntracellular ClNeuronsGABA
2000
GABA release from mouse axonal growth cones
Gao X, van den Pol A. GABA release from mouse axonal growth cones. The Journal Of Physiology 2000, 523: 629-637. PMID: 10718743, PMCID: PMC2269824, DOI: 10.1111/j.1469-7793.2000.t01-1-00629.x.Peer-Reviewed Original ResearchConceptsGABA releaseSynapse formationGrowth conesSpontaneous GABA releaseAxonal growth conesHypothalamic neuronsTransmitter phenotypeAxon terminalsNeurotransmitter receptorsTransgenic miceAction potentialsGABAProtein kinase C activityNeuronal membranesAxonsNeuronal developmentGreen fluorescent proteinKinase C activityNeuronsVesicular mechanismPKC activationFluorescent proteinC activityLow levelsRelease