2021
Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior
Yasumoto Y, Stoiljkovic M, Kim JD, Sestan-Pesa M, Gao XB, Diano S, Horvath TL. Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior. Molecular Psychiatry 2021, 26: 2740-2752. PMID: 33879866, PMCID: PMC8056795, DOI: 10.1038/s41380-021-01105-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnxietyFemaleHippocampusMaleMiceMice, KnockoutMicrogliaNeural PathwaysNeuronsSynapsesUncoupling Protein 2ConceptsAnxiety-like behaviorReactive oxygen speciesMicroglia-synapse contactsSpine synapse numberHippocampal circuit functionNeuronal circuit dysfunctionMicroglial productionVentral hippocampusCircuit dysfunctionSpine synapsesSynapse numberAdult brainTransient riseMitochondrial ROS generationMicrogliaBrain functionConditional ablationPhagocytic inclusionsSynaptic elementsProtein 2ROS generationSignificant reductionCircuit functionConsequent accumulationOxygen species
2017
Molecular and cellular reorganization of neural circuits in the human lineage
Sousa AMM, Zhu Y, Raghanti MA, Kitchen RR, Onorati M, Tebbenkamp ATN, Stutz B, Meyer KA, Li M, Kawasawa YI, Liu F, Perez RG, Mele M, Carvalho T, Skarica M, Gulden FO, Pletikos M, Shibata A, Stephenson AR, Edler MK, Ely JJ, Elsworth JD, Horvath TL, Hof PR, Hyde TM, Kleinman JE, Weinberger DR, Reimers M, Lifton RP, Mane SM, Noonan JP, State MW, Lein ES, Knowles JA, Marques-Bonet T, Sherwood CC, Gerstein MB, Sestan N. Molecular and cellular reorganization of neural circuits in the human lineage. Science 2017, 358: 1027-1032. PMID: 29170230, PMCID: PMC5776074, DOI: 10.1126/science.aan3456.Peer-Reviewed Original ResearchConceptsSingle-cell transcriptomic dataDistinct functional categoriesDistinct cell typesBiosynthesis genesTranscriptome sequencingHuman lineageTranscriptomic dataFunctional categoriesCellular reorganizationExpression differencesPhylogenetic reorganizationFunctional analysisCell typesGenesCellular featuresCellular differencesHuman specificityNeural circuitsLineagesMultiple levelsReorganizationSequencingHumansChimpanzeesAdult humans
2010
Fgfr2 Is Required for the Development of the Medial Prefrontal Cortex and Its Connections with Limbic Circuits
Stevens HE, Smith KM, Maragnoli ME, Fagel D, Borok E, Shanabrough M, Horvath TL, Vaccarino FM. Fgfr2 Is Required for the Development of the Medial Prefrontal Cortex and Its Connections with Limbic Circuits. Journal Of Neuroscience 2010, 30: 5590-5602. PMID: 20410112, PMCID: PMC2868832, DOI: 10.1523/jneurosci.5837-09.2010.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexCerebral cortexFibroblast growth factor receptorCKO miceExcitatory neuronsPrefrontal cortexCortical neuron developmentEntire cerebral cortexRadial glial cellsSpecific fibroblast growth factor receptorsGrowth factor receptorGABAergic neuronsLimbic circuitsCortical neuronsGlial cellsSubcortical stationsBed nucleusCortical developmentLimbic systemStria terminalisSynaptic terminalsSecondary decreaseNeuronal precursorsVentricular zoneNeuron development
2007
Neurobiology of Feeding and Energy Expenditure
Gao Q, Horvath TL. Neurobiology of Feeding and Energy Expenditure. Annual Review Of Neuroscience 2007, 30: 367-398. PMID: 17506645, DOI: 10.1146/annurev.neuro.30.051606.094324.Peer-Reviewed Original ResearchConceptsEnergy expenditureNeurobiology of feedingPeripheral metabolic signalsBrain homeostatic systemsMechanism of actionBrain involvementChronic regulationPharmacological techniquesNeuronal controlNeuronal mechanismsEnergy homeostasisComplex feeding behaviorHomeostatic systemMetabolic signalsFeeding behaviorInvolvementCurrent understandingBrain
2006
Synaptic 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
The 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 processes
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 inputsActivationBrain Circuits Regulating Energy Homeostasis
Horvath TL, Diano S, Tschöp M. Brain Circuits Regulating Energy Homeostasis. The Neuroscientist 2004, 10: 235-246. PMID: 15155062, DOI: 10.1177/1073858403262151.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainEnergy MetabolismHomeostasisHormonesHumansNeural PathwaysNeuropeptidesObesitySignal Transduction
2003
Estradiol affects axo-somatic contacts of neuroendocrine cells in the arcuate nucleus of adult rats
Parducz A, Zsarnovszky A, Naftolin F, Horvath TL. Estradiol affects axo-somatic contacts of neuroendocrine cells in the arcuate nucleus of adult rats. Neuroscience 2003, 117: 791-794. PMID: 12654332, DOI: 10.1016/s0306-4522(02)00967-3.Peer-Reviewed Original ResearchConceptsAxo-somatic contactsArcuate nucleusSynaptic plasticityGABAergic axo-somatic synapsesMorphological synaptic plasticityAxo-somatic synapsesEffects of estradiolSynapse quantificationArcuate neuronsTracer FluorogoldGonadal steroidsAnterior pituitaryAdult ratsHypophysiotropic neuronsMedian eminenceNervous systemTransient decreaseSystemic applicationNeuroendocrine cellsDisector methodNeuronsNumerical densityEstradiolFluorogoldCells
2000
Estrogen effects on tyrosine hydroxylase-immunoreactive cells in the ventral mesencephalon of the female rat: further evidence for the two cell hypothesis of dopamine function
Zsarnovszky A, Scalise T, Horvath T, Naftolin F. Estrogen effects on tyrosine hydroxylase-immunoreactive cells in the ventral mesencephalon of the female rat: further evidence for the two cell hypothesis of dopamine function. Brain Research 2000, 868: 363-366. PMID: 10854590, DOI: 10.1016/s0006-8993(00)02323-4.Peer-Reviewed Original ResearchConceptsSubstantia nigra compactaFemale ratsTyrosine hydroxylaseVentral mesencephalic dopaminergic neuronsTyrosine hydroxylase-immunoreactive cellsMesencephalic dopaminergic neuronsVentral tegmental areaTH-immunoreactive perikaryaDifferential effectsVentral mesencephalonTH immunoreactivityDopaminergic neuronsEstrogen effectsEstradiol benzoateTegmental areaMidbrain neuronsInterfascicular nucleusDopamine functionCell hypothesisRatsCell countingNeuronsPresent studyFurther evidenceOVX
1999
Brain Uncoupling Protein 2: Uncoupled Neuronal Mitochondria Predict Thermal Synapses in Homeostatic Centers
Horvath T, Warden C, Hajos M, Lombardi A, Goglia F, Diano S. Brain Uncoupling Protein 2: Uncoupled Neuronal Mitochondria Predict Thermal Synapses in Homeostatic Centers. Journal Of Neuroscience 1999, 19: 10417-10427. PMID: 10575039, PMCID: PMC6782406, DOI: 10.1523/jneurosci.19-23-10417.1999.Peer-Reviewed Original ResearchConceptsC-Fos-expressing cellsPeripheral energy homeostasisHormone-releasing hormoneHypothalamic neuronal populationsCorticotropin-releasing factorMelanin-concentrating hormoneMitochondria of neuronsUCP2 proteinPeripheral hormonesProximal dendritesNeuropeptide YGonadal steroidsModulates neurotransmissionAxon terminalsBasal brainLocal brainNeuronal populationsAxonal processesNeuronal mitochondriaPeptidergic circuitsBrain circuitsEnergy homeostasisCold exposureNeuronsEndocrine processesSynaptic 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
1998
Monosynaptic Pathway Between the Arcuate Nucleus Expressing Glial Type II Iodothyronine 5′‐Deiodinase mRNA and the Median Eminence‐Projective TRH Cells of the Rat Paraventricular Nucleus
Diano S, Naftolin F, Goglia F, Csernus V, Horvath T. Monosynaptic Pathway Between the Arcuate Nucleus Expressing Glial Type II Iodothyronine 5′‐Deiodinase mRNA and the Median Eminence‐Projective TRH Cells of the Rat Paraventricular Nucleus. Journal Of Neuroendocrinology 1998, 10: 731-742. PMID: 9792325, DOI: 10.1046/j.1365-2826.1998.00204.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArcuate Nucleus of HypothalamusFemaleFluorescent DyesImmunohistochemistryIn Situ HybridizationIodide PeroxidaseIsoenzymesMaleMedian EminenceNeural PathwaysNeurogliaParaventricular Hypothalamic NucleusPhytohemagglutininsRatsRats, Sprague-DawleyRNA, MessengerStilbamidinesThyrotropin-Releasing HormoneSegregation of the intra- and extrahypothalamic neuropeptide Y and catecholaminergic inputs on paraventricular neurons, including those producing thyrotropin-releasing hormone
Diano S, Naftolin F, Goglia F, Horvath T. Segregation of the intra- and extrahypothalamic neuropeptide Y and catecholaminergic inputs on paraventricular neurons, including those producing thyrotropin-releasing hormone. Peptides 1998, 75: 117-126. PMID: 9802401, DOI: 10.1016/s0167-0115(98)00060-3.Peer-Reviewed Original ResearchConceptsParvicellular paraventricular nucleusMedian forebrain bundleProximal dendritesTRH neuronsDistal dendritesCell bodiesTRH cellsNPY inputAsymmetric synapsesCatecholaminergic inputsTyrosine hydroxylaseDendritic spinesInvolvement of NPYNumber of NPYThyrotropin-releasing hormone (TRH) mRNATH-immunoreactive fibersThyroid feedbackThyrotropin-releasing hormoneFood deprivationLight microscopic examinationTRH immunoreactive cellsNPY fibersNPY releaseHypothalamic NPYCatecholaminergic neurons
1997
Evidence for a direct neuronal pathway from the suprachiasmatic nucleus to the gonadotropin‐releasing hormone system: Combined tracing and light and electron microscopic immunocytochemical studies
Van Der Beek E, Horvath T, Wiegant V, Van Den Hurk R, Buijs R. Evidence for a direct neuronal pathway from the suprachiasmatic nucleus to the gonadotropin‐releasing hormone system: Combined tracing and light and electron microscopic immunocytochemical studies. The Journal Of Comparative Neurology 1997, 384: 569-579. PMID: 9259490, DOI: 10.1002/(sici)1096-9861(19970811)384:4<569::aid-cne6>3.0.co;2-0.Peer-Reviewed Original ResearchConceptsSuprachiasmatic nucleusFemale ratsGnRH systemGnRH-immunoreactive cell bodiesGonadotropin-releasing hormone (GnRH) neuronsDaily LH surgesImplantation of estrogenOvariectomized rats resultsRostral ventrolateral portionGonadotropin-releasing hormone (GnRH) systemVasoactive intestinal polypeptideElectron microscopic immunocytochemical studyHormone neuronsGnRH neuronsIntestinal polypeptideLH surgeMonosynaptic pathwayPutative transmittersAnterograde tracerPreoptic areaNeuronal pathwaysRats resultsVentrolateral portionBilateral projectionsFemale rodents