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
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 Research
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
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 mechanismCellsNarcolepsyHypocretinNorepinephrineAcetylcholineHypocretin (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
Melanin 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, GlutamateReceptors, G-Protein-CoupledReceptors, 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 mRNA
1998
Presynaptic and Postsynaptic Actions and Modulation of Neuroendocrine Neurons by a New Hypothalamic Peptide, Hypocretin/Orexin
van den Pol A, Gao X, Obrietan K, Kilduff T, Belousov A. Presynaptic and Postsynaptic Actions and Modulation of Neuroendocrine Neurons by a New Hypothalamic Peptide, Hypocretin/Orexin. Journal Of Neuroscience 1998, 18: 7962-7971. PMID: 9742163, PMCID: PMC6793026, DOI: 10.1523/jneurosci.18-19-07962.1998.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsArcuate Nucleus of HypothalamusCadmiumCalciumCarrier ProteinsCells, CulturedDose-Response Relationship, DrugElectric StimulationEnzyme InhibitorsEvoked PotentialsFeeding BehaviorFluorescent DyesFura-2Gamma-Aminobutyric AcidGlutamic AcidIntracellular Signaling Peptides and ProteinsMembrane PotentialsMolecular Sequence DataNeuronsNeuropeptidesNeurosecretory SystemsNeurotransmitter AgentsOrexinsPatch-Clamp TechniquesPresynaptic TerminalsSignal TransductionTetrodotoxinThapsigarginConceptsLateral hypothalamusSynaptic activityNeuroendocrine neuronsWhole-cell patch-clamp recordingsNew hypothalamic peptidesLateral hypothalamic neuronsAmino acid transmittersHypothalamic regulatory systemPatch-clamp recordingsHypocretin/orexinPerifornical areaPostsynaptic actionsOrexigenic peptideHypocretin-1Hypothalamic circuitsHypocretin peptidesHypothalamic neuronsHypothalamic slicesArcuate nucleusHypocretin-2Postsynaptic receptorsAxonal inputsHypothalamic peptidesFeeding centerAxon terminalsThe hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity
de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg E, Gautvik VT, Bartlett FS, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG. The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 322-327. PMID: 9419374, PMCID: PMC18213, DOI: 10.1073/pnas.95.1.322.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCarrier ProteinsChromosomesConsensus SequenceHomeostasisHypothalamus, PosteriorIntracellular Signaling Peptides and ProteinsMaleMiceMolecular Sequence DataNeuronsNeuropeptidesNeurotransmitter AgentsOrexinsProtein PrecursorsRatsRats, WistarSecretinSynaptic VesiclesConceptsGut hormone secretinLateral hypothalamic areaNeuronal cell bodiesLarge granular vesiclesPosterior hypothalamusHypothalamic areaHypothalamic neuronsHippocampal neuronsCell bodiesGranular vesiclesHcrt peptidesHormone secretinNeuronsHypocretinNeuroexcitatory activityPeptidesPutative precursorBrainstemThalamusHypothalamusImmunoreactivityCNSNeurotransmittersSecretinProtein products