2022
ACh signaling modulates activity of the GABAergic signaling network in the basolateral amygdala and behavior in stress-relevant paradigms
Mineur YS, Mose TN, Maibom KL, Pittenger ST, Soares AR, Wu H, Taylor SR, Huang Y, Picciotto MR. ACh signaling modulates activity of the GABAergic signaling network in the basolateral amygdala and behavior in stress-relevant paradigms. Molecular Psychiatry 2022, 27: 4918-4927. PMID: 36050437, PMCID: PMC10718266, DOI: 10.1038/s41380-022-01749-7.Peer-Reviewed Original ResearchConceptsBasolateral amygdalaBLA neuronsBalance of inhibitoryHuman mood disordersLight-dark boxGABA interneuronsPV neuronsVIP neuronsCalmodulin-dependent protein kinase IIMale miceACh levelsMood disordersTail suspensionNeuronal activityNeuron subtypesAcetylcholineChronic stressInhibitory signalingBalance of activityHomeostatic functionsBLA activityStress-induced changesNeuronsSocial defeatProtein kinase II
2020
Implications of Oligomeric Amyloid-Beta (oAβ42) Signaling through α7β2-Nicotinic Acetylcholine Receptors (nAChRs) on Basal Forebrain Cholinergic Neuronal Intrinsic Excitability and Cognitive Decline
George AA, Vieira JM, Xavier-Jackson C, Gee MT, Cirrito JR, Bimonte-Nelson HA, Picciotto MR, Lukas RJ, Whiteaker P. Implications of Oligomeric Amyloid-Beta (oAβ42) Signaling through α7β2-Nicotinic Acetylcholine Receptors (nAChRs) on Basal Forebrain Cholinergic Neuronal Intrinsic Excitability and Cognitive Decline. Journal Of Neuroscience 2020, 41: 555-575. PMID: 33239400, PMCID: PMC7821864, DOI: 10.1523/jneurosci.0876-20.2020.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsBasal ForebrainCell LineCognitive DysfunctionElectrophysiological PhenomenaFemaleGenotypeHumansMaleMaze LearningMiceMice, TransgenicNeuronsParasympathetic Nervous SystemPeptide FragmentsSignal TransductionConceptsBasal forebrain cholinergic neuronsNeuronal intrinsic excitabilityAlzheimer's diseaseCholinergic neuronsDiagonal bandIntrinsic excitabilityAPP/PS1 transgenic miceCognitive declineCharacteristics of ADMedial septum-diagonal bandNicotinic acetylcholine receptor subtypesOligomeric amyloid betaAction potential firing rateForebrain cholinergic neuronsPS1 transgenic miceHorizontal diagonal bandLevels of amyloidSeptum-diagonal bandCurrent-clamp recordingsAcetylcholine receptor subtypesAction potential afterhyperpolarizationAge-matched littermatesOrganotypic slice culturesSpatial reference memoryHomomeric α7Positive modulation of NMDA receptors by AGN-241751 exerts rapid antidepressant-like effects via excitatory neurons
Pothula S, Liu RJ, Wu M, Sliby AN, Picciotto MR, Banerjee P, Duman RS. Positive modulation of NMDA receptors by AGN-241751 exerts rapid antidepressant-like effects via excitatory neurons. Neuropsychopharmacology 2020, 46: 799-808. PMID: 33059355, PMCID: PMC8027594, DOI: 10.1038/s41386-020-00882-7.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsMedial prefrontal cortexRapid antidepressant-like effectsGluN2B-containing NMDARsPositive allosteric modulatorsNMDAR positive allosteric modulatorExcitatory neuronsExerts antidepressant-like effectsAntidepressant-like behavioral effectsPrefrontal cortexBehavioral effectsAkt/mTORAntidepressant-like actionChronic unpredictable stressNMDA receptor activityRecent preclinical studiesMajor depressive disorderSpecific knockdownParvalbumin inhibitory neuronsCellular triggersSynaptic proteinsGlutamatergic systemNMDAR activityClinical trialsDepressive disorderAcetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances learning of cue-reward contingency
Crouse RB, Kim K, Batchelor HM, Girardi EM, Kamaletdinova R, Chan J, Rajebhosale P, Pittenger ST, Role LW, Talmage DA, Jing M, Li Y, Gao XB, Mineur YS, Picciotto MR. Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances learning of cue-reward contingency. ELife 2020, 9: e57335. PMID: 32945260, PMCID: PMC7529459, DOI: 10.7554/elife.57335.Peer-Reviewed Original ResearchConceptsBasolateral amygdalaCue-reward learningActivity of neuronsReward-related eventsNucleus basalisBLA responsesACh levelsPredictors of rewardTerminal fibersNeuron activityReward-predictive cuesCalcium indicatorsAChNeutral cuesEmotional stimuliAversive stimuliReward retrievalTask acquisitionAmygdalaSalient eventsMiceACh sensorTerminal activityQuick acquisitionCuesImpaired hypocretin/orexin system alters responses to salient stimuli in obese male mice
Tan Y, Hang F, Liu ZW, Stoiljkovic M, Wu M, Tu Y, Han W, Lee AM, Kelley C, Hajos M, Lu L, de Lecea L, de Araujo I, Picciotto M, Horvath TL, Gao XB. Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice. Journal Of Clinical Investigation 2020, 130: 4985-4998. PMID: 32516139, PMCID: PMC7456212, DOI: 10.1172/jci130889.Peer-Reviewed Original ResearchConceptsHcrt cellsObese miceDiet-induced obese miceObese male miceExcessive energy intakeNeuropeptide hypocretin/orexinHypocretin/orexinHcrt neuronsMale miceHcrt systemClinical studiesCommon causeSynaptic transmissionObese animalsEnergy intakeAcute stressCognitive functionSalient stimuliAlters responsesExact mechanismMiceHomeostatic regulationNeuronal networksBehavioral changesNeurons
2019
Role of Neuronal VEGF Signaling in the Prefrontal Cortex in the Rapid Antidepressant Effects of Ketamine
Deyama S, Bang E, Wohleb ES, Li XY, Kato T, Gerhard DM, Dutheil S, Dwyer JM, Taylor SR, Picciotto MR, Duman RS. Role of Neuronal VEGF Signaling in the Prefrontal Cortex in the Rapid Antidepressant Effects of Ketamine. American Journal Of Psychiatry 2019, 176: 388-400. PMID: 30606046, PMCID: PMC6494682, DOI: 10.1176/appi.ajp.2018.17121368.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeutralizingBehavior, AnimalExcitatory Amino Acid AntagonistsGene Knockdown TechniquesGene Knockout TechniquesIn Vitro TechniquesKetamineMiceNeuronsPrefrontal CortexQuinazolinesSignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsNeuronal vascular endothelial growth factorVascular endothelial growth factorMedial prefrontal cortexRapid antidepressant actionsAntidepressant actionIntra-mPFC infusionSystemic ketamineBehavioral actionsFlk-1Conventional monoamine-based antidepressantsPrefrontal cortexRole of VEGFRapid antidepressant effectsTreatment-resistant depressionMethyl-d-aspartate receptor antagonist ketamineNeuron-specific deletionMonoamine-based antidepressantsNeuron-specific knockoutViral-mediated knockdownEndothelial growth factorVEGF-Flk-1Synaptogenic actionsAntidepressant effectsSynaptogenic effectsLocal knockdown
2018
Striatin-1 is a B subunit of protein phosphatase PP2A that regulates dendritic arborization and spine development in striatal neurons
Li D, Musante V, Zhou W, Picciotto MR, Nairn AC. Striatin-1 is a B subunit of protein phosphatase PP2A that regulates dendritic arborization and spine development in striatal neurons. Journal Of Biological Chemistry 2018, 293: 11179-11194. PMID: 29802198, PMCID: PMC6052221, DOI: 10.1074/jbc.ra117.001519.Peer-Reviewed Original ResearchConceptsSerine/threonine phosphatase PP2AStriatin-interacting phosphataseRNA knockdown approachB subunitSTRIPAK complexPhosphatase PP2AProtein phosphataseMultiprotein complexesKnockdown approachStriatin familyMutant constructsStriatal neuronal culturesPP2ANeuronal developmentPrimary striatal neuronal culturesDendritic phenotypeKnockdown modelSynapse formationSubunitsSpine developmentSelective roleReduced expressionNeuron maturationNeuronal culturesStriatal neurons
2017
Bidirectional Regulation of Aggression in Mice by Hippocampal Alpha-7 Nicotinic Acetylcholine Receptors
Lewis AS, Pittenger ST, Mineur YS, Stout D, Smith PH, Picciotto MR. Bidirectional Regulation of Aggression in Mice by Hippocampal Alpha-7 Nicotinic Acetylcholine Receptors. Neuropsychopharmacology 2017, 43: 1267-1275. PMID: 29114104, PMCID: PMC5916354, DOI: 10.1038/npp.2017.276.Peer-Reviewed Original ResearchConceptsΑ7 nAChRsDentate gyrusNicotinic acetylcholine receptorsGTS-21Resident-intruder interactionsAlpha 7 nicotinic acetylcholine receptorAcetylcholine receptorsΑ7 nicotinic acetylcholine receptorExcitatory-inhibitory balancePromising therapeutic interventionGranule cell activityAggressive behaviorResident-intruder testHippocampal α7Wild-type controlsUnderlying neurobiological substratesGABAergic interneuronsMale micePotential neural circuitsRegulation of aggressionGranule cellsTherapeutic interventionsPartial agonistBrain regionsCell activity
2015
DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons
Engmann O, Giralt A, Gervasi N, Marion-Poll L, Gasmi L, Filhol O, Picciotto MR, Gilligan D, Greengard P, Nairn AC, Hervé D, Girault JA. DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons. Nature Communications 2015, 6: 10099. PMID: 26639316, PMCID: PMC4675091, DOI: 10.1038/ncomms10099.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalBrainCaffeineCalmodulin-Binding ProteinsCentral Nervous System StimulantsChlorocebus aethiopsCocaineCOS CellsDendritic SpinesDopamine and cAMP-Regulated Phosphoprotein 32EnvironmentFluorescence Recovery After PhotobleachingImmunoblottingImmunohistochemistryIn Vitro TechniquesMass SpectrometryMiceMice, Inbred C57BLMutationNeostriatumNeuronsNucleus AccumbensPhosphorylationRatsRats, Sprague-DawleyRewardConceptsAdducin phosphorylationCytoskeletal proteinsActin filamentsMolecular pathwaysCellular mechanismsEnvironmental changesPhosphorylationDARPP-32Striatal neuronsAdducinMutant miceSynaptic stabilityProteinCascadeMultiple effectsEnvironmental effectsBindsDendritic spinesNeuronsModification of responsesBrief exposurePathwayInteractionFilamentsEnrichment
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 protein
2012
Nicotine, Food Intake, and Activation of POMC Neurons
Picciotto MR, Mineur YS. Nicotine, Food Intake, and Activation of POMC Neurons. Neuropsychopharmacology 2012, 38: 245-245. PMID: 23147487, PMCID: PMC3521975, DOI: 10.1038/npp.2012.163.Peer-Reviewed Original ResearchAcetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior
Picciotto MR, Higley MJ, Mineur YS. Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior. Neuron 2012, 76: 116-129. PMID: 23040810, PMCID: PMC3466476, DOI: 10.1016/j.neuron.2012.08.036.Peer-Reviewed Original ResearchConceptsBrain areasAlters neuronal excitabilityAbility of acetylcholineNeuronal networksNervous system functionGroups of neuronsCholinergic modulationReceptor subtypesNeuronal excitabilityFood intakeSynaptic transmissionNeuronal populationsSynaptic plasticityAcetylcholineSynaptic propertiesDrug abuseSite of releaseNeuromodulatorsClassical roleOngoing stimulusNeuronsDiverse effectsSystem functionResponseCholinergicNicotinic Regulation of Energy Homeostasis
Zoli M, Picciotto MR. Nicotinic Regulation of Energy Homeostasis. Nicotine & Tobacco Research 2012, 14: 1270-1290. PMID: 22990212, PMCID: PMC3611985, DOI: 10.1093/ntr/nts159.Peer-Reviewed Original ResearchConceptsEnergy homeostasisCellular targetsPossible molecular targetsPrimary psychoactive substanceCell typesNicotinic acetylcholine receptor subtypesEnergy metabolismAcetylcholine receptor subtypesAbility of nicotineEffects of nicotineRegulation of feedingMolecular targetsFunctional featuresRegulationNicotinic regulationHomeostasisReceptor subtypesNAChR subtypesTobacco smokeBody weightNeuroendocrine systemRecent studiesNicotineMetabolismMammalsAgRP 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
2011
Plasticity of Prefrontal Attention Circuitry: Upregulated Muscarinic Excitability in Response to Decreased Nicotinic Signaling Following Deletion of α5 or β2 Subunits
Tian MK, Bailey CD, De Biasi M, Picciotto MR, Lambe EK. Plasticity of Prefrontal Attention Circuitry: Upregulated Muscarinic Excitability in Response to Decreased Nicotinic Signaling Following Deletion of α5 or β2 Subunits. Journal Of Neuroscience 2011, 31: 16458-16463. PMID: 22072695, PMCID: PMC3240894, DOI: 10.1523/jneurosci.3600-11.2011.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAconitineAge FactorsAnalysis of VarianceAnimalsAtropineDihydro-beta-ErythroidineIntracellular Signaling Peptides and ProteinsMaleMembrane PotentialsMiceMice, KnockoutNeuronal PlasticityNeuronsNeuropeptidesNeurotransmitter AgentsNicotineNicotinic AntagonistsOrexinsPatch-Clamp TechniquesPrefrontal CortexReceptors, MuscarinicReceptors, NicotinicSignal TransductionUp-RegulationConceptsLayer VI neuronsNicotinic receptorsCholinergic excitationCholinergic receptorsPrefrontal cortexExcitatory muscarinic receptorsPrefrontal attention circuitryMuscarinic cholinergic receptorsMuscarinic acetylcholine receptorsAcute brain slicesWild-type miceWhole-cell recordingsΒ2 subunitNicotinic receptor subunitsMedial prefrontal cortexPyramidal neuronsMuscarinic receptorsNicotinic signalingLayer VIAttention circuitryCholinergic stimulationBrain slicesNicotinic stimulationAcetylcholine receptorsTiming of excitationFACS purification of immunolabeled cell types from adult rat brain
Guez-Barber D, Fanous S, Harvey BK, Zhang Y, Lehrmann E, Becker KG, Picciotto MR, Hope BT. FACS purification of immunolabeled cell types from adult rat brain. Journal Of Neuroscience Methods 2011, 203: 10-18. PMID: 21911005, PMCID: PMC3221768, DOI: 10.1016/j.jneumeth.2011.08.045.Peer-Reviewed Original ResearchConceptsFluorescence-activated cell sortingCell typesPromoter-driven reporter geneBrain tissueExtracellular proteinsFACS procedureReporter geneFACS purificationRat brainReal-time PCRMolecular analysisSorted cellsCell sortingAdult rat brainTime PCRIntact cell bodiesTransgenic miceMolecular alterationsNeuN antibodyQuantitative assayCell bodiesAvailable antibodiesBrainTissueGenesNicotine Decreases Food Intake Through Activation of POMC Neurons
Mineur YS, Abizaid A, Rao Y, Salas R, DiLeone RJ, Gündisch D, Diano S, De Biasi M, Horvath TL, Gao XB, Picciotto MR. Nicotine Decreases Food Intake Through Activation of POMC Neurons. Science 2011, 332: 1330-1332. PMID: 21659607, PMCID: PMC3113664, DOI: 10.1126/science.1201889.Peer-Reviewed Original ResearchConceptsFood intakePOMC neuronsNicotine decreases food intakeDecrease food intakePro-opiomelanocortin (POMC) neuronsΑ3β4 nicotinic acetylcholine receptorsHypothalamic melanocortin systemNicotine-induced decreasesMelanocortin-4 receptorNicotinic acetylcholine receptorsAnorexic effectDecrease appetiteSmoking cessationSynaptic mechanismsMelanocortin systemNovel treatmentsBody weightAcetylcholine receptorsNeurobiological mechanismsNeuronsIntakeSubsequent activationAppetiteActivationReceptorsAn Instructive Role for Patterned Spontaneous Retinal Activity in Mouse Visual Map Development
Xu HP, Furman M, Mineur YS, Chen H, King SL, Zenisek D, Zhou ZJ, Butts DA, Tian N, Picciotto MR, Crair MC. An Instructive Role for Patterned Spontaneous Retinal Activity in Mouse Visual Map Development. Neuron 2011, 70: 1115-1127. PMID: 21689598, PMCID: PMC3119851, DOI: 10.1016/j.neuron.2011.04.028.Peer-Reviewed Original ResearchConceptsSpontaneous retinal activityRetinal activityRetinal ganglion cell projectionsEye-specific segregationGanglion cell projectionsSpontaneous retinal wavesActivity-dependent refinementRetinal ganglion cellsMouse visual systemComplex neural circuitsEye of originRetinal wavesGanglion cellsRetinotopic refinementNeuronal activitySpontaneous activityMammalian visual systemAcetylcholine receptorsNeuronal connectivityMammalian brainNeural circuitsOverall activity levelsActivity levelsBrainVisual systemFACS Identifies Unique Cocaine-Induced Gene Regulation in Selectively Activated Adult Striatal Neurons
Guez-Barber D, Fanous S, Golden SA, Schrama R, Koya E, Stern AL, Bossert JM, Harvey BK, Picciotto MR, Hope BT. FACS Identifies Unique Cocaine-Induced Gene Regulation in Selectively Activated Adult Striatal Neurons. Journal Of Neuroscience 2011, 31: 4251-4259. PMID: 21411666, PMCID: PMC3073079, DOI: 10.1523/jneurosci.6195-10.2011.Peer-Reviewed Original ResearchConceptsStriatal neuronsFluorescence-activated cell sortingNeural activity marker FosCocaine-induced locomotionActivity marker FosAdult striatal neuronsUnique gene expression profileP38 MAPK signalingCell-type specificityGene expression profilesSmall proportionTransgenic ratsActivated neuronsImmediate early genesMolecular neuroadaptationsSpecific neuronsGene regulationBehavioral effectsNeuronsAbused drugsMAPK signalingExpression profilesProtein productsCocaineLacZ gene
2009
The membrane cytoskeletal protein adducin is phosphorylated by protein kinase C in D1 neurons of the nucleus accumbens and dorsal striatum following cocaine administration
Lavaur J, Mineur YS, Picciotto MR. The membrane cytoskeletal protein adducin is phosphorylated by protein kinase C in D1 neurons of the nucleus accumbens and dorsal striatum following cocaine administration. Journal Of Neurochemistry 2009, 111: 1129-1137. PMID: 19780900, PMCID: PMC2810345, DOI: 10.1111/j.1471-4159.2009.06405.x.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsBenzazepinesBenzophenanthridinesCalmodulin-Binding ProteinsCocaineCorpus StriatumDopamine AntagonistsDopamine Uptake InhibitorsDose-Response Relationship, DrugEnzyme InhibitorsGene Expression RegulationGreen Fluorescent ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutNeuronsNucleus AccumbensPhosphorylationProtein Kinase CRacloprideReceptors, Dopamine D1Time FactorsConceptsProtein kinase CAdducin phosphorylationKinase CActin-binding proteinsFamily of proteinsPhosphorylation of adducinCytoskeletal protein adducinActin dynamicsCytoskeletal rearrangementsPhosphorylation stateCytoskeletal proteinsAdducinF-actinPhosphorylationNeuronal cytoskeletonCellular architectureProteinSynaptic functionMorphological changesCytoskeletonMedium spiny neuronsSpectrinRegimen of cocaineActinRegulation