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 ResearchMeSH KeywordsAgouti-Related ProteinAnimalsAnorexia NervosaDioxygenasesHumansHypothalamusMiceModels, AnimalNeuronsConceptsVesicular 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 ResearchMeSH KeywordsAnimalsFeeding BehaviorHypothalamusMaleMiceMice, TransgenicNerve NetNeuronsObesityOrexinsStress, PsychologicalConceptsHcrt 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
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
2010
Experience‐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
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
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 area
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 transmissionGABA, 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
1999
Kainate Acts at Presynaptic Receptors to Increase GABA Release From Hypothalamic Neurons
Liu Q, Patrylo P, Gao X, van den Pol A. Kainate Acts at Presynaptic Receptors to Increase GABA Release From Hypothalamic Neurons. Journal Of Neurophysiology 1999, 82: 1059-1062. PMID: 10444697, DOI: 10.1152/jn.1999.82.2.1059.Peer-Reviewed Original ResearchNeurotrophin‐3 potentiates excitatory GABAergic synaptic transmission in cultured developing hypothalamic neurones of the rat
Gao X, van den Pol A. Neurotrophin‐3 potentiates excitatory GABAergic synaptic transmission in cultured developing hypothalamic neurones of the rat. The Journal Of Physiology 1999, 518: 81-95. PMID: 10373691, PMCID: PMC2269394, DOI: 10.1111/j.1469-7793.1999.0081r.x.Peer-Reviewed Original ResearchMeSH Keywords6-Cyano-7-nitroquinoxaline-2,3-dioneAnimalsCalciumCarbazolesCells, CulturedElectric StimulationEnzyme InhibitorsExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsGamma-Aminobutyric AcidHypothalamusIndole AlkaloidsMembrane PotentialsNeuronsNeurotrophin 3Patch-Clamp TechniquesProtein-Tyrosine KinasesRatsSynapsesSynaptic TransmissionTetrodotoxinConceptsSpontaneous postsynaptic currentsFrequency of GABANT-3 effectsNeurotrophin-3Postsynaptic currentsHypothalamic neuronesMature neuronesWhole-cell patch-clamp recordingsMiniature post-synaptic currentsGABAergic synaptic transmissionMiniature postsynaptic currentsDose-dependent potentiationPresence of tetrodotoxinAction potential frequencyPeripheral nervous systemPatch-clamp recordingsTyrosine kinase inhibitorsMean amplitudePost-synaptic currentsNon-selective tyrosine kinase inhibitorRat hypothalamic neuronesGABA excitationGABA releaseGABAergic synapsesPresynaptic locus
1998
Glutamate Inhibits GABA Excitatory Activity in Developing Neurons
van den Pol A, Gao X, Patrylo P, Ghosh P, Obrietan K. Glutamate Inhibits GABA Excitatory Activity in Developing Neurons. Journal Of Neuroscience 1998, 18: 10749-10761. PMID: 9852609, PMCID: PMC6793361, DOI: 10.1523/jneurosci.18-24-10749.1998.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornCalciumCells, CulturedCerebral CortexEmbryo, MammalianExcitatory Postsynaptic PotentialsGABA AntagonistsGamma-Aminobutyric AcidGene ExpressionGlutamic AcidGramicidinHypothalamusIn Vitro TechniquesNeuronsPatch-Clamp TechniquesPresynaptic TerminalsPropionatesRatsRats, Sprague-DawleyReceptors, Metabotropic GlutamateSpinal CordConceptsGroup III mGluRsExcitatory actionGABA activityGroup II metabotropic glutamate receptorsFura-2 digital imagingSynapse formationBrain developmentInhibitory roleAgonist L-AP4Excitatory GABA actionsGlutamate-mediated inhibitionMetabotropic glutamate receptorsSpinal cord neuronsMajor inhibitory neurotransmitterWhole-cell recordingsSimilar inhibitory actionBrain GABAEarly brain developmentExcitatory roleGABA releaseL-AP4Excitatory transmitterGABA actionHypothalamic neuronsCord neuronsGABA-Dependent Firing of Glutamate-Evoked Action Potentials at AMPA/Kainate Receptors in Developing Hypothalamic Neurons
Gao X, Chen G, van den Pol A. GABA-Dependent Firing of Glutamate-Evoked Action Potentials at AMPA/Kainate Receptors in Developing Hypothalamic Neurons. Journal Of Neurophysiology 1998, 79: 716-726. PMID: 9463435, DOI: 10.1152/jn.1998.79.2.716.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidAction potentialsHypothalamic neuronsAMPA/kainate receptorsN-methyl-D-aspartate receptorsGlutamate-mediated excitationAdult mammalian CNSFire action potentialsMajor inhibitory roleExcitatory functionGlutamate responseGlutamate receptorsKainate receptorsMammalian CNSMaximal effectSlight temporal delayNeuronal circuitsInhibitory roleNeuronsReceptorsBroad time windowDepolarizationGlutamatePresent studySimilar results