2021
Drp1 is required for AgRP neuronal activity and feeding
Jin S, Yoon NA, Liu ZW, Song JE, Horvath TL, Kim JD, Diano S. Drp1 is required for AgRP neuronal activity and feeding. ELife 2021, 10: e64351. PMID: 33689681, PMCID: PMC7946429, DOI: 10.7554/elife.64351.Peer-Reviewed Original ResearchConceptsAgRP neuronal activityFatty acid oxidationAgRP neuronsNeuronal activityAgRP neuronal functionHypothalamic AgRP neuronsBody weight regulationMitochondrial fatty acid utilizationWhole-body energy homeostasisHypothalamic orexigenic agoutiFatty acid utilizationAcid oxidationFat massCKO miceNeuronal activationPeptide-1Body weightNeuronal functionOrexigenic agoutiEnergy homeostasisMitochondrial fissionSignificant decreaseEnergy expenditureNeuronsAcid utilization
2020
AgRP neurons control compulsive exercise and survival in an activity-based anorexia model
Miletta MC, Iyilikci O, Shanabrough M, Šestan-Peša M, Cammisa A, Zeiss CJ, Dietrich MO, Horvath TL. AgRP neurons control compulsive exercise and survival in an activity-based anorexia model. Nature Metabolism 2020, 2: 1204-1211. PMID: 33106687, DOI: 10.1038/s42255-020-00300-8.Peer-Reviewed Original ResearchConceptsAgRP neuronsActivity-based anorexia modelAgRP neuronal activityVivo fiber photometryFood-restricted miceFood-restricted animalsCompulsive exerciseAnorexia modelHypothalamic agoutiNeuropeptide YExercise volumeFood intakeMouse modelNeuronal activityFiber photometryDaily activationNeuronal circuitsPsychiatric conditionsAnorexia nervosaChemogenetic toolsNeuronsLong-term behavioral impactElevated fat contentVoluntary cessationFat content
2017
Plasticity of calcium-permeable AMPA glutamate receptors in Pro-opiomelanocortin neurons
Suyama S, Ralevski A, Liu ZW, Dietrich MO, Yada T, Simonds SE, Cowley MA, Gao XB, Diano S, Horvath TL. Plasticity of calcium-permeable AMPA glutamate receptors in Pro-opiomelanocortin neurons. ELife 2017, 6: e25755. PMID: 28762946, PMCID: PMC5538821, DOI: 10.7554/elife.25755.Peer-Reviewed Original ResearchConceptsExcitatory postsynaptic currentsPOMC neuronsCP-AMPARsFasted stateAMPAR-mediated excitatory postsynaptic currentsCalcium-permeable AMPA glutamate receptorsInhibition of EPSCsHigh-fat diet exposurePOMC neuronal activityPro-opiomelanocortin (POMC) neuronsCalcium-permeable AMPARsElevated leptin levelsAMPA glutamate receptorsAmplitude of mEPSCsFood deprivationEntry of calciumAMPA receptor complexesDiet exposureLeptin levelsPostsynaptic currentsEPSC amplitudeGlutamate receptorsNeuronal activityExtracellular calciumLinear current-voltage relationshipEndothelial HIF-1α Enables Hypothalamic Glucose Uptake to Drive POMC Neurons
Varela L, Suyama S, Huang Y, Shanabrough M, Tschöp M, Gao XB, Giordano FJ, Horvath TL. Endothelial HIF-1α Enables Hypothalamic Glucose Uptake to Drive POMC Neurons. Diabetes 2017, 66: db161106. PMID: 28292966, PMCID: PMC5440016, DOI: 10.2337/db16-1106.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalBlotting, WesternEndotheliumEnergy MetabolismFood DeprivationGene Knockdown TechniquesGlucoseHyperphagiaHypothalamusHypoxia-Inducible Factor 1, alpha SubunitImmunohistochemistryMiceMicroscopy, ElectronMitochondriaNeuronsPatch-Clamp TechniquesPro-OpiomelanocortinReal-Time Polymerase Chain ReactionConceptsPOMC neuronsGlucose uptakePOMC neuronal activityHypothalamic proopiomelanocortin (POMC) neuronsHypoxia-inducible factor-1αProopiomelanocortin neuronsVascular impairmentGlucose administrationMetabolic disordersNeuronal activityMetabolic environmentFactor-1αImpaired functioningEndothelial cellsNeuronsFood deprivationVivoCentral controlHypothalamusMiceAdministrationUptakeImpairment(S)Pot on Mitochondria: Cannabinoids Disrupt Cellular Respiration to Limit Neuronal Activity
Harkany T, Horvath TL. (S)Pot on Mitochondria: Cannabinoids Disrupt Cellular Respiration to Limit Neuronal Activity. Cell Metabolism 2017, 25: 8-10. PMID: 28076767, DOI: 10.1016/j.cmet.2016.12.020.Peer-Reviewed Original Research
2015
Hypothalamic POMC neurons promote cannabinoid-induced feeding
Koch M, Varela L, Kim JG, Kim JD, Hernández-Nuño F, Simonds SE, Castorena CM, Vianna CR, Elmquist JK, Morozov YM, Rakic P, Bechmann I, Cowley MA, Szigeti-Buck K, Dietrich MO, Gao XB, Diano S, Horvath TL. Hypothalamic POMC neurons promote cannabinoid-induced feeding. Nature 2015, 519: 45-50. PMID: 25707796, PMCID: PMC4496586, DOI: 10.1038/nature14260.Peer-Reviewed Original ResearchConceptsPOMC neuronsΒ-endorphinHypothalamic pro-opiomelanocortin (POMC) neuronsOpioid peptide β-endorphinHypothalamic POMC neuronsPromotion of feedingPro-opiomelanocortin (POMC) neuronsCannabinoid receptor 1CB1R activityPOMC activitySated miceHormone releaseHypothalamic administrationFood intakeCentral regulationNeuronal activityParadoxical increaseCB1RReceptor 1POMC cellsNeuronsMitochondrial adaptationsDecreased activityPOMC geneUnsuspected role
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 areasHypothalamusNeuronsAgrp Neurons Mediate Sirt1's Action on the Melanocortin System and Energy Balance: Roles for Sirt1 in Neuronal Firing and Synaptic Plasticity
Dietrich MO, Antunes C, Geliang G, Liu ZW, Borok E, Nie Y, Xu AW, Souza DO, Gao Q, Diano S, Gao XB, Horvath TL. Agrp Neurons Mediate Sirt1's Action on the Melanocortin System and Energy Balance: Roles for Sirt1 in Neuronal Firing and Synaptic Plasticity. Journal Of Neuroscience 2010, 30: 11815-11825. PMID: 20810901, PMCID: PMC2965459, DOI: 10.1523/jneurosci.2234-10.2010.Peer-Reviewed Original ResearchConceptsFood intakeMelanocortin systemAgRP neuronal activityAnorexigenic POMC neuronsHypothalamic melanocortin systemAction of SIRT1Negative energy balanceAgRP neuronsPOMC neuronsCre-lox technologyInhibitory toneMC4R antagonistFat massLean massSynaptic inputsNeuronal activityNeuronal firingAdult miceBody weightSIRT1 inhibitorSynaptic plasticityCalorie restrictionMelanocortin receptorsSIRT1 activityBody metabolism
2009
Nesfatin-1-Regulated Oxytocinergic Signaling in the Paraventricular Nucleus Causes Anorexia through a Leptin-Independent Melanocortin Pathway
Maejima Y, Sedbazar U, Suyama S, Kohno D, Onaka T, Takano E, Yoshida N, Koike M, Uchiyama Y, Fujiwara K, Yashiro T, Horvath TL, Dietrich MO, Tanaka S, Dezaki K, Oh-I S, Hashimoto K, Shimizu H, Nakata M, Mori M, Yada T. Nesfatin-1-Regulated Oxytocinergic Signaling in the Paraventricular Nucleus Causes Anorexia through a Leptin-Independent Melanocortin Pathway. Cell Metabolism 2009, 10: 355-365. PMID: 19883614, DOI: 10.1016/j.cmet.2009.09.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnorexiaAutocrine CommunicationCalcium-Binding ProteinsDNA-Binding ProteinsLeptinMelanocortinsMiceNerve Tissue ProteinsNeuroendocrine CellsNucleobindinsOxytocinParacrine CommunicationParaventricular Hypothalamic NucleusPro-OpiomelanocortinRatsRats, ZuckerSignal TransductionSolitary NucleusConceptsNucleus tractus solitariusNesfatin-1Oxytocin releaseParacrine/autocrine actionsNesfatin-1 neuronsParaventricular nucleus functionPro-opiomelanocortin (POMC) neuronsZucker fatty ratsOxytocin receptor antagonistOxytocin terminalsPVN neuronsTractus solitariusReceptor antagonistCentral injectionParaventricular nucleusAutocrine actionMelanocortin pathwayNeuronal activityNeural pathwaysPVNAnorexiaNeuronsNucleus functionOxytocinImmunoelectron micrographs
2008
Exercise-Induced Synaptogenesis in the Hippocampus Is Dependent on UCP2-Regulated Mitochondrial Adaptation
Dietrich MO, Andrews ZB, Horvath TL. Exercise-Induced Synaptogenesis in the Hippocampus Is Dependent on UCP2-Regulated Mitochondrial Adaptation. Journal Of Neuroscience 2008, 28: 10766-10771. PMID: 18923051, PMCID: PMC3865437, DOI: 10.1523/jneurosci.2744-08.2008.Peer-Reviewed Original ResearchConceptsSynaptic plasticityVoluntary exerciseEssential organellesUCP2 functionProtein-2 mRNA expressionDendritic spine synapsesBioenergetic adaptationMitochondrial metabolismMitochondrial oxygen consumptionMitochondrial numberEnergetic needsMitochondrial adaptationsMitochondrial mechanismsExercise inducesDentate gyrusStratum radiatumSpine synapsesCA1 regionGlial morphologyHippocampal formationNeuronal activityGranule cellsAction potentialsNeuronal morphologyMRNA expressionUCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals
Andrews ZB, Liu ZW, Walllingford N, Erion DM, Borok E, Friedman JM, Tschöp MH, Shanabrough M, Cline G, Shulman GI, Coppola A, Gao XB, Horvath TL, Diano S. UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals. Nature 2008, 454: 846-851. PMID: 18668043, PMCID: PMC4101536, DOI: 10.1038/nature07181.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsCarnitine O-PalmitoyltransferaseFatty AcidsFeeding BehaviorGene Expression RegulationGhrelinHypothalamusIon ChannelsMembrane Potential, MitochondrialMiceMitochondriaMitochondrial ProteinsNeuronsNeuropeptide YPhosphorylationReactive Oxygen SpeciesSynapsesUncoupling Protein 2ConceptsNPY/AgRP neuronsAgRP neuronsNeuronal activityCo-express neuropeptide YGut-derived hormone ghrelinAgRP neuronal activityArcuate nucleus neuronsFatty acid oxidation pathwayHypothalamic mitochondrial respirationG protein-coupled receptorsGhrelin actionNeuropeptide YNucleus neuronsHormone ghrelinFood intakeGhrelinFree radicalsSynaptic plasticityNeuronal functionIntracellular mechanismsNeuronsMitochondrial mechanismsProtein 2Mitochondrial proliferationRobust changes
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 handlingMiceWakefulnessNeuronal control of energy homeostasis
Gao Q, Horvath TL. Neuronal control of energy homeostasis. FEBS Letters 2007, 582: 132-141. PMID: 18061579, PMCID: PMC4113225, DOI: 10.1016/j.febslet.2007.11.063.Peer-Reviewed Original ResearchConceptsEnergy homeostasisNeuronal controlMolecular genetic toolsPeripheral metabolic hormonesHypothalamic neuronal circuitsLong-term energy balanceBody energy homeostasisGenetic toolsHomeostatic machineryMetabolic hormonesNeuronal activityNeuronal circuitryBody weightEnergy intakeNeuronal circuitsCellular mechanismsHomeostasisBehavioral techniquesLife spanKey mechanismMachineryIntakeHormone
2006
Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite
Abizaid A, Liu ZW, Andrews ZB, Shanabrough M, Borok E, Elsworth JD, Roth RH, Sleeman MW, Picciotto MR, Tschöp MH, Gao XB, Horvath TL. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. Journal Of Clinical Investigation 2006, 116: 3229-3239. PMID: 17060947, PMCID: PMC1618869, DOI: 10.1172/jci29867.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAppetiteDopamineFluorescent Antibody TechniqueGhrelinMaleMesencephalonMiceMice, Inbred C57BLMice, KnockoutNeuronsNucleus AccumbensPatch-Clamp TechniquesPeptide HormonesRatsRats, Sprague-DawleyReceptors, GhrelinReceptors, G-Protein-CoupledTime FactorsVentral Tegmental AreaConceptsVentral tegmental areaGHSR-deficient miceGHSR-dependent mannerGut hormone ghrelinDopamine neuronal activityMidbrain dopamine neuronsMesolimbic reward circuitrySynaptic input organizationPeripheral ghrelinRebound feedingVTA administrationOrexigenic effectDopamine turnoverGHSR antagonistDopamine neuronsHypothalamic centersTegmental areaHormone ghrelinNucleus accumbensGhrelinNeuronal activitySynapse formationReward circuitryInput organizationFeeding schedule