2021
From Molecule to Behavior: Hypocretin/orexin Revisited From a Sex-dependent Perspective
Gao XB, Horvath TL. From Molecule to Behavior: Hypocretin/orexin Revisited From a Sex-dependent Perspective. Endocrine Reviews 2021, 43: 743-760. PMID: 34792130, PMCID: PMC9277634, DOI: 10.1210/endrev/bnab042.Peer-Reviewed Original ResearchCerebellar Kv3.3 potassium channels activate TANK-binding kinase 1 to regulate trafficking of the cell survival protein Hax-1
Zhang Y, Varela L, Szigeti-Buck K, Williams A, Stoiljkovic M, Šestan-Peša M, Henao-Mejia J, D’Acunzo P, Levy E, Flavell RA, Horvath TL, Kaczmarek LK. Cerebellar Kv3.3 potassium channels activate TANK-binding kinase 1 to regulate trafficking of the cell survival protein Hax-1. Nature Communications 2021, 12: 1731. PMID: 33741962, PMCID: PMC7979925, DOI: 10.1038/s41467-021-22003-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell SurvivalCerebellumExosomesFemaleInterneuronsIntracellular Signaling Peptides and ProteinsMaleMiceMutationPhenotypeProtein Serine-Threonine KinasesProtein TransportShaw Potassium ChannelsSignal TransductionConceptsTank Binding Kinase 1HAX-1Kv3.3 potassium channelMultivesicular bodiesKinase 1TANK-binding kinase 1Activation of caspasesAnti-apoptotic proteinsPotassium channelsMembrane proteinsBiochemical pathwaysCerebellar neuronsChannels bindCell deathTBK1 activityIon channelsMutant channelsCellular constituentsTraffickingKv3.3 channelsProteinNeuronal survivalMutationsChannel inactivationCaspases
2016
Feeding Behavior: Hypocretin/Orexin Neurons Act between Food Seeking and Eating
Gao XB, Horvath TL. Feeding Behavior: Hypocretin/Orexin Neurons Act between Food Seeking and Eating. Current Biology 2016, 26: r845-r847. PMID: 27676302, DOI: 10.1016/j.cub.2016.07.069.Peer-Reviewed Original ResearchMeSH KeywordsEatingFeeding BehaviorIntracellular Signaling Peptides and ProteinsNeuronsNeuropeptidesOrexins
2014
Function and Dysfunction of Hypocretin/Orexin: An Energetics Point of View
Gao XB, Horvath T. Function and Dysfunction of Hypocretin/Orexin: An Energetics Point of View. Annual Review Of Neuroscience 2014, 37: 101-116. PMID: 24821311, DOI: 10.1146/annurev-neuro-071013-013855.Peer-Reviewed Original ResearchAnimalsArousalEnergy MetabolismHumansHypothalamic Area, LateralIntracellular Signaling Peptides and ProteinsMotivationNarcolepsyNeuropeptidesOrexins
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 ResearchMeSH KeywordsAnimalsCocaineConditioning, PsychologicalExcitatory Postsynaptic PotentialsHypothalamusIntracellular Signaling Peptides and ProteinsLong-Term PotentiationMiceMice, Inbred C57BLNeuronal PlasticityNeuronsNeuropeptidesOrexinsSynapsesConceptsCAMP 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
Direct inhibition of hypocretin/orexin neurons in the lateral hypothalamus by nociceptin/orphanin FQ blocks stress-induced analgesia in rats
Gerashchenko D, Horvath TL, Xie X. Direct inhibition of hypocretin/orexin neurons in the lateral hypothalamus by nociceptin/orphanin FQ blocks stress-induced analgesia in rats. Neuropharmacology 2010, 60: 543-549. PMID: 21195099, PMCID: PMC3031765, DOI: 10.1016/j.neuropharm.2010.12.026.Peer-Reviewed Original ResearchMeSH KeywordsAnalgesiaAnalysis of VarianceAnimalsCell CountHypothalamic Area, LateralImmunohistochemistryIntracellular Signaling Peptides and ProteinsMaleMicroinjectionsMicroscopy, ElectronNeuronsNeuropeptidesOpioid PeptidesOrexinsPain MeasurementPain PerceptionProto-Oncogene Proteins c-fosRatsRats, Sprague-DawleyReceptors, OpioidRestraint, PhysicalStatistics, NonparametricStress, PhysiologicalConceptsStress-induced analgesiaHcrt neuronsLateral hypothalamusPerifornical areaNociceptin/orphanin FQ systemHypocretin/orexin neuronsNociceptin/orphanin FQHcrt neuronal activityDirect inhibitionThermal pain thresholdThermal nociceptive testsHypocretin/orexinFos immunohistochemistryOrexin neuronsBilateral microinjectionIntracerebroventricular injectionPain thresholdNociceptive testsOrphanin FQOFQ receptorMouse modelNeuronal activityBrain areasHypothalamusNeurons
2008
Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia
Xie X, Wisor JP, Hara J, Crowder TL, LeWinter R, Khroyan TV, Yamanaka A, Diano S, Horvath TL, Sakurai T, Toll L, Kilduff TS. Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia. Journal Of Clinical Investigation 2008, 118: 2471-2481. PMID: 18551194, PMCID: PMC2423866, DOI: 10.1172/jci35115.Peer-Reviewed Original ResearchMeSH KeywordsAnalgesiaAnimalsAtaxin-3Behavior, AnimalBrainCalciumCytoplasmElectrophysiologyFemaleHypothalamus, PosteriorImmunohistochemistryIntracellular Signaling Peptides and ProteinsMaleMembrane PotentialsMiceMice, Inbred C57BLMice, TransgenicNarcotic AntagonistsNeuronsNeuropeptidesNociceptin ReceptorNuclear ProteinsOpioid PeptidesOrexinsPain ThresholdPresynaptic TerminalsReaction TimeReceptors, OpioidStress, PhysiologicalTetrodotoxinTranscription FactorsConceptsStress-induced analgesiaHcrt neuronsWild-type miceHypocretin/orexinNociceptin/orphanin FQMouse hypothalamic slicesCorticotropin-releasing factorPatch-clamp recordingsOrexin/ataxinPostsynaptic effectsPresynaptic releaseOrphanin FQElectron microscopic levelHypothalamic slicesSynaptic contactsHcrt-1Hcrt systemMouse modelAnalgesiaClamp recordingsPeptidergic systemsAction potentialsBrain tissueNeuronsInput resistance
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
Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque
Downs JL, Dunn MR, Borok E, Shanabrough M, Horvath TL, Kohama SG, Urbanski HF. Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque. Neurobiology Of Aging 2006, 28: 1286-1295. PMID: 16870307, DOI: 10.1016/j.neurobiolaging.2006.05.025.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAgingAnalysis of VarianceAnimalsHypothalamic Area, LateralIn Situ HybridizationIntracellular Signaling Peptides and ProteinsLocus CoeruleusMacaca mulattaMaleNeuronsNeuropeptidesOrexinsTyrosine 3-MonooxygenaseConceptsLateral hypothalamic areaPoor sleep qualityLocus coeruleusNoradrenergic locus coeruleusSleep qualityNeuron numberRhesus macaquesAge-related decreaseTyrosine hydroxylase mRNAAge-related lossMale rhesus macaquesOrexin innervationOrexin neuronsOrexin neuropeptidesAge-related declineB immunoreactivityHypothalamic areaNeuronal changesElderly humansAxon densityLC contributeHydroxylase mRNANonhuman primatesOld animalsAdult animals
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 ResearchMeSH KeywordsAnimalsDendritesHypothalamusImmunohistochemistryIntracellular Signaling Peptides and ProteinsMaleMembrane PotentialsMiceMice, TransgenicNeuronal PlasticityNeuronsNeuropeptidesObesityOrexinsPatch-Clamp TechniquesSleep Initiation and Maintenance DisordersSynapsesConceptsHypocretin 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
2004
Interaction between the Corticotropin-Releasing Factor System and Hypocretins (Orexins): A Novel Circuit Mediating Stress Response
Winsky-Sommerer R, Yamanaka A, Diano S, Borok E, Roberts AJ, Sakurai T, Kilduff TS, Horvath TL, de Lecea L. Interaction between the Corticotropin-Releasing Factor System and Hypocretins (Orexins): A Novel Circuit Mediating Stress Response. Journal Of Neuroscience 2004, 24: 11439-11448. PMID: 15601950, PMCID: PMC6730356, DOI: 10.1523/jneurosci.3459-04.2004.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsArousalBrainBrain ChemistryCorticotropin-Releasing HormoneFemaleHypothalamusImmunohistochemistryIn Vitro TechniquesIntracellular Signaling Peptides and ProteinsMaleMembrane PotentialsMiceMice, KnockoutNeural PathwaysNeuronsNeuropeptidesOrexin ReceptorsOrexinsReceptors, Corticotropin-Releasing HormoneReceptors, G-Protein-CoupledReceptors, NeuropeptideRecombinant Fusion ProteinsStress, PhysiologicalConceptsCorticotropin-releasing factorHypocretinergic neuronsHypocretin neuronsCorticotropin-Releasing Factor SystemCRF-immunoreactive terminalsHypocretin-expressing neuronsRelease of hypocretinsStability of arousalMaintenance of arousalHypocretinergic cellsHypothalamic slicesLateral hypothalamusAntagonist astressinHypocretinergic systemNeuropeptide hypocretinStressor stimuliPeptidergic systemsAcute stressHypocretinNeuronsStress responseFactor systemMembrane potentialPhysiological inputsActivation
2003
Fasting Activates the Nonhuman Primate Hypocretin (Orexin) System and Its Postsynaptic Targets
Diano S, Horvath B, Urbanski HF, Sotonyi P, Horvath TL. Fasting Activates the Nonhuman Primate Hypocretin (Orexin) System and Its Postsynaptic Targets. Endocrinology 2003, 144: 3774-3778. PMID: 12933647, DOI: 10.1210/en.2003-0274.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsCarrier ProteinsChlorocebus aethiopsEatingFastingFemaleHypothalamusIntracellular Signaling Peptides and ProteinsNeuropeptidesOrexinsProto-Oncogene Proteins c-fosConceptsPerifornical regionArcuate nucleusHypothalamic regulationC-Fos-expressing cellsLateral hypothalamic cellsC-fosMedial preoptic areaVariety of endocrineC-fos expressionDiverse brain regionsHCRT axonsLeptin levelsNuclear c-FosDorsomedial hypothalamusAsymmetric synapsesBasal forebrainPresent studyPostsynaptic targetsDorsomedial nucleusNeuropeptide Y.Preoptic areaThalamic nucleiHcrt neuronsHcrt systemAxon terminals
2000
Evidence of NPY Y5 receptor involvement in food intake elicited by orexin A in sated rats
Dube M, Horvath T, Kalra P, Kalra S. Evidence of NPY Y5 receptor involvement in food intake elicited by orexin A in sated rats. Peptides 2000, 21: 1557-1560. PMID: 11068104, DOI: 10.1016/s0196-9781(00)00311-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAppetite DepressantsAppetite RegulationCarrier ProteinsEatingFeeding BehaviorInjections, IntraventricularIntracellular Signaling Peptides and ProteinsMaleNaphthalenesNerve Tissue ProteinsNeuronsNeuropeptidesOrexin ReceptorsOrexinsPyrimidinesRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledReceptors, NeuropeptideReceptors, Neuropeptide YSignal TransductionWeight GainConceptsOrexigenic peptideReceptor antagonistSated ratsNPY Y1 receptor antagonistNPY-producing neuronsPotent orexigenic peptideNPY Y5 receptor antagonistsY1 receptor antagonistY5 receptor antagonistsOrexin AIntracerebroventricular injectionY5 receptorsNeuropeptide YReceptor involvementFood intakeStimulate feedingNeuronsAntagonistRatsFeedingOrexinCurrent resultsFunctional linkHypothalamusNPYEvidence that NPY Y1 receptors are involved in stimulation of feeding by orexins (hypocretins) in sated rats
Jain M, Horvath T, Kalra P, Kalra S. Evidence that NPY Y1 receptors are involved in stimulation of feeding by orexins (hypocretins) in sated rats. Peptides 2000, 87: 19-24. PMID: 10710284, DOI: 10.1016/s0167-0115(99)00102-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsEatingFeeding BehaviorIntracellular Signaling Peptides and ProteinsMaleNeuropeptidesOrexin ReceptorsOrexinsPeptides, CyclicRatsReceptors, G-Protein-CoupledReceptors, NeuropeptideReceptors, Neuropeptide YSatiationConceptsNeuropeptide YLateral hypothalamic areaArcuate nucleusY1 receptorParaventricular nucleusSelective NPY Y1 receptor antagonistNPY Y1 receptor antagonistNPY Y1 receptorY1 receptor antagonistStimulation of feedingAdult male ratsDose-dependent mannerOrexigenic peptideOrexin ANPY receptorsExcitatory effectsHypothalamic areaHypothalamic appetiteReceptor antagonistMale ratsSated ratsOrexinNeural sitesReceptorsNPYergic
1999
Hypocretin (orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system
Horvath T, Peyron C, Diano S, Ivanov A, Aston‐Jones G, Kilduff T, van den Pol A. Hypocretin (orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system. The Journal Of Comparative Neurology 1999, 415: 145-159. PMID: 10545156, DOI: 10.1002/(sici)1096-9861(19991213)415:2<145::aid-cne1>3.0.co;2-2.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsChlorocebus aethiopsFemaleHypothalamusImmunohistochemistryIntracellular Signaling Peptides and ProteinsLocus CoeruleusMacaca fascicularisMaleMicroscopy, ElectronMSH Release-Inhibiting HormoneNeuropeptidesNeurotransmitter AgentsNorepinephrineOrexinsPresynaptic TerminalsRatsRats, Sprague-DawleyTetrodotoxinTyrosine 3-MonooxygenaseConceptsLocus coeruleusSynaptic innervationNoradrenergic systemAxon terminalsTyrosine hydroxylase-immunopositive cellsAsymmetrical synaptic contactsLC-noradrenergic systemParallel electrophysiological studiesLocus coeruleus noradrenergic systemPresence of tetrodotoxinMelanin-concentrating hormoneLC neuronsAutonomic centersNoradrenergic innervationDense arborizationsExcitatory responsesHypocretin cellsSubstantia nigraSynaptic contactsHypocretin-2Lateral hypothalamusZona incertaModest depolarizationCatecholamine systemsCentral regulationSynaptic Interaction between Hypocretin (Orexin) and Neuropeptide Y Cells in the Rodent and Primate Hypothalamus: A Novel Circuit Implicated in Metabolic and Endocrine Regulations
Horvath T, Diano S, van den Pol A. Synaptic Interaction between Hypocretin (Orexin) and Neuropeptide Y Cells in the Rodent and Primate Hypothalamus: A Novel Circuit Implicated in Metabolic and Endocrine Regulations. Journal Of Neuroscience 1999, 19: 1072-1087. PMID: 9920670, PMCID: PMC6782143, DOI: 10.1523/jneurosci.19-03-01072.1999.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsChlorocebus aethiopsEndocrine GlandsFemaleHypothalamusIntracellular Signaling Peptides and ProteinsMaleMetabolismNeural PathwaysNeuronsNeuropeptide YNeuropeptidesOrexin ReceptorsOrexinsRatsRats, Sprague-DawleyReceptors, Cell SurfaceReceptors, G-Protein-CoupledReceptors, LeptinReceptors, NeuropeptideSynapsesConceptsHypothalamic functionCentral regulationHypocretin-containing neuronsLateral hypothalamic cellsLeptin receptor immunoreactivityNeuropeptide Y cellsDirect synaptic contactsNeuropeptide Y systemEndocrine regulationEndocrine processesNPY releaseReceptor immunoreactivityExcitatory actionHypocretin cellsSynaptic contactsArcuate nucleusLateral hypothalamusPrimate hypothalamusLeptin receptorSame neuronsHypothalamic cellsSynaptic regulationAdipose tissueHypocretinNPY