2010
Corticosterone Regulates Synaptic Input Organization of POMC and NPY/AgRP Neurons in Adult Mice
Gyengesi E, Liu ZW, D'Agostino G, Gan G, Horvath TL, Gao XB, Diano S. Corticosterone Regulates Synaptic Input Organization of POMC and NPY/AgRP Neurons in Adult Mice. Endocrinology 2010, 151: 5395-5402. PMID: 20843996, PMCID: PMC2954711, DOI: 10.1210/en.2010-0681.Peer-Reviewed Original ResearchConceptsNPY/AgRP neuronsSynaptic input organizationSham-operated controlsAgRP neuronsADX miceCorticosterone replacementNeuropeptide YArcuate nucleusSynaptic arrangementsInput organizationPair-fed control animalsPutative excitatory synapsesPutative inhibitory synapsesHypothalamic arcuate nucleusEffects of adrenalectomySham-operated animalsNumber of synapsesPOMC neuronsProtein (AgRP) neuronsOrexigenic actionMembrane potentialSynaptic analysisInhibitory synapsesExcitatory synapsesFood intake
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
2006
Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity
Plum L, Ma X, Hampel B, Balthasar N, Coppari R, Münzberg H, Shanabrough M, Burdakov D, Rother E, Janoschek R, Alber J, Belgardt BF, Koch L, Seibler J, Schwenk F, Fekete C, Suzuki A, Mak TW, Krone W, Horvath TL, Ashcroft FM, Brüning JC. Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. Journal Of Clinical Investigation 2006, 116: 1886-1901. PMID: 16794735, PMCID: PMC1481658, DOI: 10.1172/jci27123.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChromonesDietEatingFemaleHypoglycemic AgentsHypothalamusInsulinLeptinMaleMembrane PotentialsMiceMice, KnockoutMorpholinesNeuronsObesityPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphoinositide-3 Kinase InhibitorsPotassium ChannelsPro-OpiomelanocortinPTEN PhosphohydrolaseSecond Messenger SystemsTolbutamideConceptsPOMC neuronsATP-sensitive potassium channel activityBasal firing rateHypothalamic proopiomelanocortin (POMC) neuronsElectrical activityKATP channel activationPI3K inhibitor LY294002PTEN knockout micePotassium channel activityK inhibitor LY294002PI3K pathwayProopiomelanocortin neuronsHypothalamic receptorsICV administrationFood intakeKATP channelsKnockout miceMelanocortin systemLeptinFiring rateNeuronsMiceSTAT3 phosphorylationK pathwayInhibitor LY294002
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
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
Mitochondrial uncoupling protein 2 in the central nervous system: neuromodulator and neuroprotector
Horvath TL, Diano S, Barnstable C. Mitochondrial uncoupling protein 2 in the central nervous system: neuromodulator and neuroprotector. Biochemical Pharmacology 2003, 65: 1917-1921. PMID: 12787871, DOI: 10.1016/s0006-2952(03)00143-6.Peer-Reviewed Original ResearchConceptsMitochondrial membrane potentialInner membraneRole of UCP2Normal neuronal functionDiverse tissuesUnknown functionProtein 2Functional significanceImportant playersCentral nervous systemNeuronal functionProteinMembrane potentialNervous systemUCP2Disease statesUCPBrown adipose tissueNew avenuesMitochondriaTissueAdipose tissueUCP1Better understandingUncoupler