2021
Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward auto-activation loop in mice
Varela L, Stutz B, Song JE, Kim JG, Liu ZW, Gao XB, Horvath TL. Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward auto-activation loop in mice. Journal Of Clinical Investigation 2021, 131 PMID: 33848272, PMCID: PMC8121506, DOI: 10.1172/jci144239.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsAstrocytesHungerHypothalamusMaleMiceMice, TransgenicNeuronal PlasticityNeuronsReceptors, Prostaglandin E, EP2 SubtypeConceptsAgRP neuronsHypothalamic feeding circuitsInhibitory neurotransmitter GABAGhrelin administrationInhibitory toneAstrocytic responseMetabolic milieuProstaglandin E2Neurotransmitter GABANeuronal controlSynaptic plasticityGlial processesNeuronsNeural excitationMitochondrial adaptationsFood deprivationAstrocytesPerikaryaFeeding circuitRegion crucialFeedingObesityGABAExcitabilityChemogenetics
2018
Insulin regulates POMC neuronal plasticity to control glucose metabolism
Dodd GT, Michael NJ, Lee-Young RS, Mangiafico SP, Pryor JT, Munder AC, Simonds SE, Brüning JC, Zhang ZY, Cowley MA, Andrikopoulos S, Horvath TL, Spanswick D, Tiganis T. Insulin regulates POMC neuronal plasticity to control glucose metabolism. ELife 2018, 7: e38704. PMID: 30230471, PMCID: PMC6170188, DOI: 10.7554/elife.38704.Peer-Reviewed Original ResearchConceptsHepatic glucose productionPOMC neuronsSuch adaptive processesNutritional cuesGene expressionMolecular mechanismsGlucose metabolismInsulin receptorDiet-induced obesityTCPTPNeuronal plasticityAdaptive processHypothalamic neuronsNeuronal excitabilityGlucose productionMetabolismInsulinNeuronsRepressionNeural responsesObesityRegulationMechanismPlasticityExpression
2016
Mitochondria controlled by UCP2 determine hypoxia-induced synaptic remodeling in the cortex and hippocampus
Varela L, Schwartz ML, Horvath TL. Mitochondria controlled by UCP2 determine hypoxia-induced synaptic remodeling in the cortex and hippocampus. Neurobiology Of Disease 2016, 90: 68-74. PMID: 26777666, DOI: 10.1016/j.nbd.2016.01.004.Peer-Reviewed Original ResearchConceptsHippocampal neuronsMitochondria-endoplasmic reticulum interactionUCP2-KO miceEarly postnatal exposureLoss of synapsesOxygen tensionHigher brain regionsAdaptive mitochondrial responsesProtein 2 expressionHypothalamic circuitsPostnatal exposureKO miceSynaptic remodelingSystemic metabolismSynaptic inputsBrain cellsMetabolic controlNeuronal mitochondriaBrain regionsAdaptive responseNeuronsHippocampusMitochondrial dynamicsMetabolic challengesCortex
2014
Role of Synaptic Plasticity and EphA5-EphrinA5 Interaction Within the Ventromedial Hypothalamus in Response to Recurrent Hypoglycemia
Szepietowska B, Horvath TL, Sherwin RS. Role of Synaptic Plasticity and EphA5-EphrinA5 Interaction Within the Ventromedial Hypothalamus in Response to Recurrent Hypoglycemia. Diabetes 2014, 63: 1140-1147. PMID: 24222347, PMCID: PMC3931406, DOI: 10.2337/db13-1259.Peer-Reviewed Original ResearchConceptsRecurrent hypoglycemiaVentromedial hypothalamusEphA5 receptorNondiabetic ratsCounterregulatory responsesSynaptic plasticityAntecedent recurrent hypoglycemiaCounterregulatory hormone releaseDefective glucose counterregulationExpression of ephrinA5Counterregulatory hormone responsesIntensive insulin treatmentInsulin-induced hypoglycemiaHyperinsulinemic-hypoglycemic clamp studyGlucose infusion rateHypoglycemic clamp studiesGlucose counterregulationSynaptic coverageHypoglycemic stimulusGlucagon secretionGlucagon releaseAcute hypoglycemiaInsulin treatmentHormone releaseInfusion rate
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 proteinHypothalamic control of energy balance: insights into the role of synaptic plasticity
Dietrich MO, Horvath TL. Hypothalamic control of energy balance: insights into the role of synaptic plasticity. Trends In Neurosciences 2013, 36: 65-73. PMID: 23318157, DOI: 10.1016/j.tins.2012.12.005.Peer-Reviewed Original ResearchConceptsWhole-body energy metabolismRegion-specific expressionGenetic toolsPeripheral tissue functionsMetabolism regulationMetabolic hormone receptorsEnergy metabolismTissue functionMetabolic eventsRole of neuronsHormone receptorsRegulationGlial cellsHypothalamic controlSynaptic plasticityCentral regulationNeuronal circuitsBrain circuitsEnormous leapPlasticitySurprising findingRoleExpressionMetabolismDynamic process
2012
AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors
Dietrich MO, Bober J, Ferreira JG, Tellez LA, Mineur YS, Souza DO, Gao XB, Picciotto MR, Araújo I, Liu ZW, Horvath TL. AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors. Nature Neuroscience 2012, 15: 1108-1110. PMID: 22729177, PMCID: PMC3411867, DOI: 10.1038/nn.3147.Peer-Reviewed Original Research
2010
Agrp 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
Feeding signals and brain circuitry
Dietrich MO, Horvath TL. Feeding signals and brain circuitry. European Journal Of Neuroscience 2009, 30: 1688-1696. PMID: 19878280, DOI: 10.1111/j.1460-9568.2009.06963.x.Peer-Reviewed Original ResearchEstrogens Regulate Posttranslational Modification of Neural Cell Adhesion Molecule during the Estrogen-Induced Gonadotropin Surge
Tan O, Fadiel A, Chang A, Demir N, Jeffrey R, Horvath T, Garcia-Segura LM, Naftolin F. Estrogens Regulate Posttranslational Modification of Neural Cell Adhesion Molecule during the Estrogen-Induced Gonadotropin Surge. Endocrinology 2009, 150: 2783-2790. PMID: 19282389, DOI: 10.1210/en.2008-0927.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEstradiolEstrogensEstrous CycleFemaleGonadotropinsMiceMice, Inbred C57BLMidline Thalamic NucleiModels, AnimalNeural Cell Adhesion Molecule L1Neural Cell Adhesion MoleculesNeuronal PlasticityProtein IsoformsProtein Processing, Post-TranslationalRNA, MessengerSialic AcidsSialyltransferasesSynapsesConceptsNeural cell adhesion moleculePeriventricular areaIR-PSAPerineural spacePSA-NCAMCell adhesion moleculeAdhesion moleculesPSA-NCAM stainingExtent of stainingSialyltransferase mRNA levelsGonadotropin surgeNCAM stainingPreovulatory gonadotropinSynaptic plasticityProestrous afternoonEstrogenWestern blotProestrusIndividual neuronsRT-PCRMetestrusMRNA levelsHypothalamus tissueStainingSialyltransferase mRNA
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 handlingMiceWakefulnessEstrogen-Induced Hypothalamic Synaptic Plasticity and Pituitary Sensitization in the Control of the Estrogen-Induced Gonadotrophin Surge
Naftolin F, Garcia-Segura LM, Horvath TL, Zsarnovszky A, Demir N, Fadiel A, Leranth C, Vondracek-Klepper S, Lewis C, Chang A, Parducz A. Estrogen-Induced Hypothalamic Synaptic Plasticity and Pituitary Sensitization in the Control of the Estrogen-Induced Gonadotrophin Surge. Reproductive Sciences 2007, 14: 101-116. PMID: 17636222, DOI: 10.1177/1933719107301059.Peer-Reviewed Original ResearchConceptsGnRH secretionPituitary gonadotrophsGonadotrophin surgeSynaptic plasticityInsulinlike growth factor 1Triggering of ovulationOvarian estrogen secretionGrowth factor-1Neural cell adhesion moleculePituitary sensitizationGnRH cellsGnRH neuronsEstrogen secretionHypothalamic neuronsGonadal functionCell adhesion moleculeSex steroidsSpecific immunoneutralizationOvarian cycleGonadotrophsAdhesion moleculesEstrogenMaximal sensitizationSecretionFactor 1
2006
Synaptic Plasticity in Energy Balance Regulation
Horvath TL. Synaptic Plasticity in Energy Balance Regulation. Obesity 2006, 14: 228s-233s. PMID: 17021372, DOI: 10.1038/oby.2006.314.Peer-Reviewed Original ResearchConceptsOb/ob miceNumber of excitatoryNeuropeptide YSynaptic plasticityPOMC neuronsOb miceFood intakeBehavioral effectsLeptin receptor-deficient miceRearrangement of synapsesLeptin-deficient miceReceptor-deficient miceHypothalamic arcuate nucleusOb/obEnergy balance regulationWild-type miceInfluences brain functionObserved synaptic plasticityWild-type animalsProopiomelanocortin neuronsAnorexigenic hormonesOrexigenic hormonePost-synaptic densityGlutamate inputsExtrahypothalamic sitesSynaptic plasticity mediating leptin's effect on metabolism
Horvath TL. Synaptic plasticity mediating leptin's effect on metabolism. Progress In Brain Research 2006, 153: 47-55. PMID: 16876567, DOI: 10.1016/s0079-6123(06)53002-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHumansHypothalamusLeptinModels, NeurologicalNeural PathwaysNeuronal PlasticitySynapsesConceptsPrimate hypothalamusSynaptic plasticityEnergy homeostasisShort-term fastingLeptin effectsHypothalamic regulationSynaptic inputsNeuromodulator systemsPeptidergic circuitsHypothalamusNonhuman primatesPathological conditionsBasic wiringMetabolic statePhysiological regulationHomeostasisMetabolic circuitsRodent speciesRatsFastingMicePlasticityResponse
2005
Mitochondrial uncoupling proteins in the cns: in support of function and survival
Andrews ZB, Diano S, Horvath TL. Mitochondrial uncoupling proteins in the cns: in support of function and survival. Nature Reviews Neuroscience 2005, 6: 829-840. PMID: 16224498, DOI: 10.1038/nrn1767.Peer-Reviewed Original ResearchConceptsNeuronal functionNeurological disordersTraumatic brain injuryAmyotrophic lateral sclerosisClinical treatment strategiesMitochondrial calcium influxModels of neurodegenerationMitochondrial uncouplingFree radical productionReactive oxygen species productionNeuronal deteriorationNeuronal deathSubstantia nigraBrain injurySpinal cordVentral tegmentumTreatment strategiesOxygen species productionNeuronal microenvironmentSynaptic transmissionCalcium influxLimbic systemNeurological conditionsLateral sclerosisParkinson's diseaseThe hardship of obesity: a soft-wired hypothalamus
Horvath TL. The hardship of obesity: a soft-wired hypothalamus. Nature Neuroscience 2005, 8: 561-565. PMID: 15856063, DOI: 10.1038/nn1453.Peer-Reviewed Original ResearchConceptsFood intakeMetabolic disordersEnergy expenditureHumoral responseHomeostatic feedback loopSynaptic plasticityBrain circuitryObesityCentral therapyMetabolic phenotypeCellular mechanismsBrain anatomyMetabolic cuesIntakeDisordersCurrent knowledgeMajor advancesHeavy tollMorbidityDiabetesHypothalamusTherapyCNSMortalityMetabolic processesInput 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
CPG2 A brain- and synapse-specific protein that regulates the endocytosis of glutamate receptors
Cottrell JR, Borok E, Horvath TL, Nedivi E. CPG2 A brain- and synapse-specific protein that regulates the endocytosis of glutamate receptors. Neuron 2004, 44: 677-690. PMID: 15541315, PMCID: PMC3065105, DOI: 10.1016/j.neuron.2004.10.025.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBlotting, NorthernBlotting, WesternBrainCells, CulturedClathrin-Coated VesiclesEndocytosisHumansIn Situ HybridizationMicroscopy, ElectronMolecular Sequence DataNerve Tissue ProteinsNeuronal PlasticityNeuronsReceptors, AMPAReceptors, GlutamateReceptors, N-Methyl-D-AspartateReverse Transcriptase Polymerase Chain ReactionSynapsesConceptsGlutamate receptorsClathrin-coated vesiclesBrain-specific splice variantSynapse-specific proteinsExcitatory synapsesReceptor endocytosisSYNE-1 geneConstitutive internalizationEndocytic mechanismsSynaptic AMPA receptorsDendritic spine sizeMembrane transportSplice variantsSynaptic proteinsNMDA receptorsAMPA receptorsProteinPostsynaptic plasticityNeurotransmitter receptorsEndocytosisSynaptic strengthLong-term maintenanceReceptorsSpine sizeInternalizationThe floating blueprint of hypothalamic feeding circuits
Horvath TL, Diano S. The floating blueprint of hypothalamic feeding circuits. Nature Reviews Neuroscience 2004, 5: 662-667. PMID: 15263896, DOI: 10.1038/nrn1479.Peer-Reviewed Original ResearchConceptsHypothalamic feeding circuitsNew therapeutic avenuesMetabolic parametersFood intakeMetabolic disordersSynaptic plasticityTherapeutic avenuesLesion studiesGenetic findingsEnergy expenditureEarlier lesion studiesCircuit changesHypothalamusImportant regulatorUnexpected findingMetabolism regulationFeeding circuitFindingsIntakeAppetiteRapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin
Pinto S, Roseberry AG, Liu H, Diano S, Shanabrough M, Cai X, Friedman JM, Horvath TL. Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin. Science 2004, 304: 110-115. PMID: 15064421, DOI: 10.1126/science.1089459.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArcuate Nucleus of HypothalamusBody WeightEatingEvoked PotentialsExcitatory Postsynaptic PotentialsFeeding BehaviorGamma-Aminobutyric AcidGhrelinGlutamic AcidGreen Fluorescent ProteinsIn Vitro TechniquesLeptinLuminescent ProteinsMiceMice, ObeseMice, TransgenicNeuronal PlasticityNeuronsNeuropeptide YPatch-Clamp TechniquesPeptide HormonesPro-OpiomelanocortinRecombinant Fusion ProteinsSynapsesTetrodotoxinTransgenesConceptsProopiomelanocortin neuronsNeuropeptide YFat-derived hormone leptinBehavioral effectsOb/ob miceLeptin-deficient miceOb/obHypothalamic arcuate nucleusWild-type miceNumber of excitatoryArcuate nucleusLeptin effectsPostsynaptic currentsOb miceHormone leptinSynaptic densityInhibitory synapsesFood intakeNeuronal typesLeptinMiceNeuronsFeeding circuitRapid rewiringHours