2023
Electrical properties of dendritic spines
Zecevic D. Electrical properties of dendritic spines. Biophysical Journal 2023, 122: 4303-4315. PMID: 37837192, PMCID: PMC10698282, DOI: 10.1016/j.bpj.2023.10.008.Peer-Reviewed Original ResearchConceptsDendritic spinesIntracellular calcium concentration changesCortical pyramidal neuronsExcitatory synaptic transmissionCalcium concentration changesBasal dendritesPyramidal neuronsMushroom spinesSpine synapsesSynaptic transmissionBrain slicesVoltage-sensitive dyeNervous systemSpine neckSignificant physiological roleSynaptic signalingTwo-photon uncagingElectrical compartmentsSpineOnly experimental studiesBiochemical compartmentalizationPhysiological roleDifferent preparationsAnatomical structuresAdequate sensitivity
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 ResearchConceptsAnxiety-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
2019
Prefrontal Cortical and Behavioral Adaptations to Surgical Delivery Mediated by Metabolic Principles
Taylor-Giorlando M, Scheinost D, Ment L, Rothman D, Horvath TL. Prefrontal Cortical and Behavioral Adaptations to Surgical Delivery Mediated by Metabolic Principles. Cerebral Cortex 2019, 29: 5061-5071. PMID: 30877804, PMCID: PMC6918927, DOI: 10.1093/cercor/bhz046.Peer-Reviewed Original ResearchConceptsMode of deliverySurgical deliveryLayer 3 pyramidal neuronsAlters mitochondrial dynamicsValues of miceMurine findingsCerebral cortexPyramidal neuronsAdult behaviorHuman neonatesMaze testPrepulse inhibitionSpine synapsesPsychiatric illnessAdult miceNeuronal circuitryAnimal modelsClinical relevanceHuman clinical relevanceUCP-2Prefrontal cortexMitochondrial adaptationsImpaired performanceMitochondrial mechanismsBehavioral phenotypes
2017
mGluR2 versus mGluR3 Metabotropic Glutamate Receptors in Primate Dorsolateral Prefrontal Cortex: Postsynaptic mGluR3 Strengthen Working Memory Networks
Jin LE, Wang M, Galvin VC, Lightbourne TC, Conn PJ, Arnsten AF, Paspalas CD. mGluR2 versus mGluR3 Metabotropic Glutamate Receptors in Primate Dorsolateral Prefrontal Cortex: Postsynaptic mGluR3 Strengthen Working Memory Networks. Cerebral Cortex 2017, 28: 974-987. PMID: 28108498, PMCID: PMC5974790, DOI: 10.1093/cercor/bhx005.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsDose-Response Relationship, DrugExcitatory Amino Acid AgentsEye MovementsFemaleImage Processing, Computer-AssistedMacaca mulattaMagnetic Resonance ImagingMaleMemory, Short-TermNeuronsPost-Synaptic DensityPrefrontal CortexRatsReceptors, Metabotropic GlutamateSpatial LearningSubcellular FractionsConceptsPrimate dorsolateral prefrontal cortexMetabotropic glutamate receptorsDorsolateral prefrontal cortexGlutamate receptorsCell firingPrefrontal cortexMGluR2 positive allosteric modulatorsFocus of pathologyNovel therapeutic targetPositive allosteric modulatorsMGluR3 agonistGlutamate transmissionAstrocytic expressionGlial receptorsPostsynaptic componentsSpine synapsesInhibition of cAMPN-acetylaspartylglutamateMGluR3Therapeutic targetCognitive disordersLayer IIIMGluR2Postsynaptic cAMPAlzheimer's disease
2015
Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions
Fuchikami M, Thomas A, Liu R, Wohleb ES, Land BB, DiLeone RJ, Aghajanian GK, Duman RS. Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 8106-8111. PMID: 26056286, PMCID: PMC4491758, DOI: 10.1073/pnas.1414728112.Peer-Reviewed Original ResearchConceptsIL-PFCOptogenetic stimulationAntidepressant actionAnxiolytic effectsSystemic ketamineLayer V pyramidal neuronsSystemic ketamine administrationInfralimbic prefrontal cortexPrecise cellular mechanismsKetamine infusionKetamine administrationPyramidal neuronsAnxiolytic actionDepressed patientsSpine synapsesSynaptic responsesNeuronal inactivationRodent modelsNeuronal activityKetaminePrefrontal cortexBehavioral actionsCellular mechanismsStimulationPatientsLow circulating levels of bisphenol‐A induce cognitive deficits and loss of asymmetric spine synapses in dorsolateral prefrontal cortex and hippocampus of adult male monkeys
Elsworth JD, Jentsch JD, Groman SM, Roth RH, Redmond ED, Leranth C. Low circulating levels of bisphenol‐A induce cognitive deficits and loss of asymmetric spine synapses in dorsolateral prefrontal cortex and hippocampus of adult male monkeys. The Journal Of Comparative Neurology 2015, 523: 1248-1257. PMID: 25557059, PMCID: PMC4390445, DOI: 10.1002/cne.23735.Peer-Reviewed Original ResearchConceptsLevels of BPARegimen of exposureAdult male vervet monkeysExcitatory synaptic inputsAsymmetric spine synapsesAdult male monkeysImpact of BPADorsolateral prefrontal cortexPyramidal neuronsSpine synapsesSynaptic effectsCognitive dysfunctionMale vervet monkeysSynaptic inputsDendritic spinesPrimate brainExposure of humansMale monkeysBrain regionsCognitive deficitsLevels of bisphenolPrefrontal cortexAdverse effectsManufacture of plasticsStudies of humans
2014
Primate Phencyclidine Model of Schizophrenia: Sex-Specific Effects on Cognition, Brain Derived Neurotrophic Factor, Spine Synapses, and Dopamine Turnover in Prefrontal Cortex
Elsworth JD, Groman SM, Jentsch JD, Leranth C, Redmond DE, Kim JD, Diano S, Roth RH. Primate Phencyclidine Model of Schizophrenia: Sex-Specific Effects on Cognition, Brain Derived Neurotrophic Factor, Spine Synapses, and Dopamine Turnover in Prefrontal Cortex. The International Journal Of Neuropsychopharmacology 2014, 18: pyu048. PMID: 25522392, PMCID: PMC4438537, DOI: 10.1093/ijnp/pyu048.Peer-Reviewed Original ResearchConceptsSpine synapse numberDorsolateral prefrontal cortexDopamine turnoverPhencyclidine treatmentSpine synapsesSynapse numberCognitive deficitsPrefrontal cortexPhencyclidine modelMale monkeysJuvenile monkeysSchizophrenia-related cognitive deficitsDendritic spine synapsesIncidence of schizophreniaAdult male monkeysSex-specific effectsMessenger RNABDNF expressionNeurotrophic factorNovel treatmentsCombined groupAdult nonhumanCore symptomsCortexNonhuman primatescAMP-PKA phosphorylation of tau confers risk for degeneration in aging association cortex
Carlyle BC, Nairn AC, Wang M, Yang Y, Jin LE, Simen AA, Ramos BP, Bordner KA, Craft GE, Davies P, Pletikos M, Šestan N, Arnsten AF, Paspalas CD. cAMP-PKA phosphorylation of tau confers risk for degeneration in aging association cortex. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 5036-5041. PMID: 24707050, PMCID: PMC3977284, DOI: 10.1073/pnas.1322360111.Peer-Reviewed Original ResearchConceptsNeurofibrillary tanglesAssociation cortexAlzheimer's diseaseSpine apparatusPhosphorylated tauPattern of neurodegenerationLate-stage diseaseHigh-risk factorsNormal aged miceGenetic rodent modelsPrefrontal association cortexPrimary sensory cortexPrimary visual cortexAge-related increasePyramidal neuronsCorticocortical connectionsAged miceRisk factorsGlutamate synapsesSpine synapsesSelective vulnerabilityRodent modelsDendritic spinesSensory cortexProtein kinase phosphorylation
2010
mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists
Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS. mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists. Science 2010, 329: 959-964. PMID: 20724638, PMCID: PMC3116441, DOI: 10.1126/science.1190287.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsDendritic SpinesDepressionIntracellular Signaling Peptides and ProteinsKetamineMaleNeuronsNeuropeptidesPhenolsPiperidinesProtein BiosynthesisProtein Serine-Threonine KinasesRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateSignal TransductionSirolimusSynapsesTime FactorsTOR Serine-Threonine KinasesConceptsTreatment-resistant depressed patientsBlockade of mTORFast antidepressant actionAction of ketamineRapid antidepressant effectsRapid antidepressant responseEffects of ketamineModel of depressionAntidepressant actionAntidepressant effectsAntidepressant responseKetamine inductionStandard medicationSynaptic deficitsKetamine administrationDepressed patientsSpine synapsesNMDA antagonistsMood disordersSynapse formationKetamineMammalian targetPrefrontal cortexRapamycin (mTOR) pathwayPossible new approachBisphenol A interferes with synaptic remodeling
Hajszan T, Leranth C. Bisphenol A interferes with synaptic remodeling. Frontiers In Neuroendocrinology 2010, 31: 519-530. PMID: 20609373, PMCID: PMC2964437, DOI: 10.1016/j.yfrne.2010.06.004.Peer-Reviewed Original ResearchEffects of Estradiol on Learned Helplessness and Associated Remodeling of Hippocampal Spine Synapses in Female Rats
Hajszan T, Szigeti-Buck K, Sallam NL, Bober J, Parducz A, MacLusky NJ, Leranth C, Duman RS. Effects of Estradiol on Learned Helplessness and Associated Remodeling of Hippocampal Spine Synapses in Female Rats. Biological Psychiatry 2010, 67: 168-174. PMID: 19811775, PMCID: PMC2794927, DOI: 10.1016/j.biopsych.2009.08.017.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsBehavior, AnimalCA1 Region, HippocampalDendritic SpinesDisease Models, AnimalElectroshockEscape ReactionEstradiolEstrogensFemaleHelplessness, LearnedMicroscopy, Electron, TransmissionNeuronsOvariectomyRatsRats, Sprague-DawleyRegression AnalysisStereotaxic TechniquesStress, PsychologicalSynapsesTime FactorsConceptsHippocampal spine synapsesSpine synapsesHelpless behaviorFemale ratsSpine synapse numberNeurobiology of depressionOvariectomized female ratsEffects of estradiolPresence of estradiolElectron microscopic stereologySynaptic lossSubchronic treatmentEstradiol exposureEstradiol supplementationFemale reproductive lifeNonstressed animalsSynaptic responsesSynaptogenic effectsDepression neurobiologyMale ratsSynapse numberAntidepressant desipramineEscape testingSynapse remodelingSignificant negative correlation
2009
Dopamine
Elsworth J, Roth R. Dopamine. 2009, 539-547. DOI: 10.1016/b978-008045046-9.00683-5.Peer-Reviewed Original ResearchCo-localized peptidesDA neuron activityDopamine cell groupsDendritic spine synapsesDifferent firing patternsSpine densityDA neurotransmissionSpine synapsesParkinson's diseaseNeuron activityVolume transmissionPharmacological perspectiveCell groupsFiring patternsEndogenous mechanismsDiseaseAutoreceptorsNeurotransmissionSchizophreniaBrainSynapses
2008
Remodeling of Hippocampal Spine Synapses in the Rat Learned Helplessness Model of Depression
Hajszan T, Dow A, Warner-Schmidt JL, Szigeti-Buck K, Sallam NL, Parducz A, Leranth C, Duman RS. Remodeling of Hippocampal Spine Synapses in the Rat Learned Helplessness Model of Depression. Biological Psychiatry 2008, 65: 392-400. PMID: 19006787, PMCID: PMC2663388, DOI: 10.1016/j.biopsych.2008.09.031.Peer-Reviewed Original ResearchConceptsHippocampal spine synapsesSpine synapse lossSpine synapsesInescapable footshockEscape deficitSynapse lossDepressive behaviorHippocampal synaptic changesLoss of synapsesNonstressed control ratsStress-related disordersElectron microscopic stereologyStructural synaptic modificationsDesipramine treatmentSynaptic alterationsMotor cortexControl ratsDentate gyrusHippocampal dysfunctionMale ratsSingle injectionSynaptic changesHelplessness paradigmBehavioral effectsSynaptic modificationExercise-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 expressionBisphenol A prevents the synaptogenic response to estradiol in hippocampus and prefrontal cortex of ovariectomized nonhuman primates
Leranth C, Hajszan T, Szigeti-Buck K, Bober J, MacLusky NJ. Bisphenol A prevents the synaptogenic response to estradiol in hippocampus and prefrontal cortex of ovariectomized nonhuman primates. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 14187-14191. PMID: 18768812, PMCID: PMC2544599, DOI: 10.1073/pnas.0806139105.Peer-Reviewed Original ResearchConceptsSpine synapse formationNonhuman primate modelSynapse formationPrimate modelAbility of BPAPrefrontal cortexOvariectomized nonhuman primatesLimbic brain areasHuman BPA exposureRodent animal modelsLow exposure levelsBPA administrationDaily doseMale ratsSpine synapsesBPA exposureAnimal modelsBrain areasSynthetic xenoestrogenCognitive functionNonhuman primatesAdverse effectsExposure levelsPolycarbonate plasticsExposure measurements
2007
Bisphenol A Prevents the Synaptogenic Response to Testosterone in the Brain of Adult Male Rats
Leranth C, Szigeti-Buck K, MacLusky NJ, Hajszan T. Bisphenol A Prevents the Synaptogenic Response to Testosterone in the Brain of Adult Male Rats. Endocrinology 2007, 149: 988-994. PMID: 18048497, PMCID: PMC2275360, DOI: 10.1210/en.2007-1053.Peer-Reviewed Original ResearchConceptsAdult male ratsMedial prefrontal cortexMale ratsSpine synapsesCA1 hippocampal areaAsymmetric spine synapsesSham-operated animalsElectron microscopic stereologyImpairs synaptogenesisSynaptogenic actionsOvariectomized ratsHippocampal areaTestosterone supplementationTestosterone propionateEstrogen receptorExposure measurement dataOil vehicleCompensatory increaseIntact animalsSynthetic xenoestrogenPrefrontal cortexRatsHippocampusCastrated malesPotential mechanismsPrenatal exposure to cocaine is associated with increased number of spine synapses in rat prelimbic cortex
Morrow BA, Hajszan T, Leranth C, Elsworth JD, Roth RH. Prenatal exposure to cocaine is associated with increased number of spine synapses in rat prelimbic cortex. Synapse 2007, 61: 862-865. PMID: 17630673, DOI: 10.1002/syn.20430.Peer-Reviewed Original ResearchConceptsPrenatal exposureFemale ratsSpine synapsesPrelimbic cortexDendritic spinesCognitive deficitsLayers II/IIIPrenatal saline controlsExcitatory synaptic inputsAsymmetric spine synapsesPrenatal cocaine exposureRat prelimbic cortexYoung adult malesPhysical disector methodPyramidal neuronsSaline controlsNeuronal activationCocaine exposureExcitatory synapsesFrontal cortexSynaptic inputsAnimal modelsExcess activationPrefrontal cortexCortexEffects of Androgens and Estradiol on Spine Synapse Formation in the Prefrontal Cortex of Normal and Testicular Feminization Mutant Male Rats
Hajszan T, MacLusky NJ, Johansen JA, Jordan CL, Leranth C. Effects of Androgens and Estradiol on Spine Synapse Formation in the Prefrontal Cortex of Normal and Testicular Feminization Mutant Male Rats. Endocrinology 2007, 148: 1963-1967. PMID: 17317772, PMCID: PMC2128740, DOI: 10.1210/en.2006-1626.Peer-Reviewed Original ResearchConceptsSpine synapse formationMale ratsWild-type animalsPrefrontal cortexTfm ratsSpine synapsesAndrogen receptorSynapse formationEffects of androgensSynaptogenic actionsTfm malesGonadal steroidsSynaptogenic effectsGonadal hormonesSynaptic remodelingTfm animalsFemale monkeysRatsCortexCortical spinesCognitive effectsAndrogensReceptorsSynapsesAdult males
2006
Ghrelin controls hippocampal spine synapse density and memory performance
Diano S, Farr SA, Benoit SC, McNay EC, da Silva I, Horvath B, Gaskin FS, Nonaka N, Jaeger LB, Banks WA, Morley JE, Pinto S, Sherwin RS, Xu L, Yamada KA, Sleeman MW, Tschöp MH, Horvath TL. Ghrelin controls hippocampal spine synapse density and memory performance. Nature Neuroscience 2006, 9: 381-388. PMID: 16491079, DOI: 10.1038/nn1656.Peer-Reviewed Original ResearchConceptsHippocampal spine synapse densitySpine synapse densitySpine synapse formationGrowth hormone releaseNovel therapeutic strategiesLong-term potentiationHigher brain functionsEnhanced spatial learningGut hormonesGhrelin administrationHypothalamic actionSynapse densitySpine synapsesCA1 regionHormone releaseNeuropeptide ghrelinGhrelin bindingHippocampal formationTherapeutic strategiesMelanocortin systemGhrelinBrain areasMetabolic controlSynaptic changesSynaptic plasticityAndrogen Effects on Hippocampal CA1 Spine Synapse Numbers Are Retained in Tfm Male Rats with Defective Androgen Receptors
MacLusky NJ, Hajszan T, Johansen JA, Jordan CL, Leranth C. Androgen Effects on Hippocampal CA1 Spine Synapse Numbers Are Retained in Tfm Male Rats with Defective Androgen Receptors. Endocrinology 2006, 147: 2392-2398. PMID: 16439462, DOI: 10.1210/en.2005-0673.Peer-Reviewed Original ResearchConceptsDefective androgen receptorHippocampal synaptic responsesEstradiol benzoateAndrogen receptorMale ratsSpine synapsesTfm malesSynaptic responsesAndrogen effectsTfm mutationEffects of EBDose of EBHippocampal CA1 synapsesSpine synapse numberSesame oil vehicleDendritic spine synapsesCA1 stratum radiatumAdult male ratsHippocampal spine synapsesVehicle-injected controlsHormone-induced increaseAgonists/antagonistsWild-type animalsWild-type malesCA1 synapses
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