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 α7Impaired 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 ResearchMeSH KeywordsAnimalsFeeding BehaviorHypothalamusMaleMiceMice, TransgenicNerve NetNeuronsObesityOrexinsStress, PsychologicalConceptsHcrt 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 changesNeuronsGABA interneurons are the cellular trigger for ketamine’s rapid antidepressant actions
Gerhard DM, Pothula S, Liu RJ, Wu M, Li XY, Girgenti MJ, Taylor SR, Duman CH, Delpire E, Picciotto M, Wohleb ES, Duman RS. GABA interneurons are the cellular trigger for ketamine’s rapid antidepressant actions. Journal Of Clinical Investigation 2020, 130: 1336-1349. PMID: 31743111, PMCID: PMC7269589, DOI: 10.1172/jci130808.Peer-Reviewed Original ResearchConceptsRapid antidepressant actionsAntidepressant actionGABA interneuronsMedial prefrontal cortexCell-specific knockdownPrinciple neuronsPrefrontal cortexDeletion of GluN2BSingle subanesthetic doseBehavioral actionsAction of ketamineNMDA receptor antagonistExcitatory postsynaptic currentsCellular triggersMajor unmet needKetamine's rapid antidepressant actionsGABA subtypeGluN2B-NMDARsSST interneuronsPostsynaptic currentsReceptor antagonistDepressed patientsSubanesthetic doseExtracellular glutamateMood disorders
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
2016
Evaluation of the Nicotinic Acetylcholine Receptor-Associated Proteome at Baseline and Following Nicotine Exposure in Human and Mouse Cortex
McClure-Begley TD, Esterlis I, Stone KL, Lam TT, Grady SR, Colangelo CM, Lindstrom JM, Marks MJ, Picciotto MR. Evaluation of the Nicotinic Acetylcholine Receptor-Associated Proteome at Baseline and Following Nicotine Exposure in Human and Mouse Cortex. ENeuro 2016, 3: eneuro.0166-16.2016. PMID: 27559543, PMCID: PMC4985585, DOI: 10.1523/eneuro.0166-16.2016.Peer-Reviewed Original ResearchConceptsPutative interacting proteinsQuantitative proteomic assessmentProtein-protein interactionsTemporal cortex tissueChaperone familyMood disordersInteracting proteinProtein complexesPresynaptic neurotransmitter releaseNovel etiological mechanismsNicotine exposureProteomic assessmentProteomeNicotinic acetylcholine receptorsMouse cortexProteinHigh-affinity nAChRsΒ2 subunitCortex of miceMaintenance of smokingNew treatment targetsResult of smokingNeurotransmitter releaseAcetylcholine receptorsPrimary functionGABA interneurons mediate the rapid antidepressant-like effects of scopolamine
Wohleb ES, Wu M, Gerhard DM, Taylor SR, Picciotto MR, Alreja M, Duman RS. GABA interneurons mediate the rapid antidepressant-like effects of scopolamine. Journal Of Clinical Investigation 2016, 126: 2482-2494. PMID: 27270172, PMCID: PMC4922686, DOI: 10.1172/jci85033.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsMajor depressive disorderMedial prefrontal cortexRapid antidepressant-like effectsRapid antidepressant effectsM1-AChRAntidepressant effectsGABA interneuronsSST interneuronsM1-type muscarinic acetylcholine receptorsNonselective muscarinic acetylcholine receptor antagonistMuscarinic acetylcholine receptor antagonistAcetylcholine receptor antagonistMuscarinic acetylcholine receptorsViral-mediated knockdownPromising pharmacological targetActivity-dependent synapticAntidepressant therapyGABAergic neuronsSomatostatin interneuronsGlutamatergic neuronsSocioeconomic burdenGABAergic interneuronsGlutamatergic interneuronsReceptor antagonist
2014
GABAergic and glutamatergic efferents of the mouse ventral tegmental area
Taylor SR, Badurek S, Dileone RJ, Nashmi R, Minichiello L, Picciotto MR. GABAergic and glutamatergic efferents of the mouse ventral tegmental area. The Journal Of Comparative Neurology 2014, 522: 3308-3334. PMID: 24715505, PMCID: PMC4107038, DOI: 10.1002/cne.23603.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell CountCholine O-AcetyltransferaseDependovirusEfferent PathwaysGABAergic NeuronsGlutamate DecarboxylaseGlutamatesLuminescent ProteinsMiceMice, Inbred C57BLMice, TransgenicStilbamidinesSubstance PTyrosine 3-MonooxygenaseVentral Tegmental AreaVesicular Glutamate Transport Protein 2Vesicular Inhibitory Amino Acid Transport ProteinsConceptsVentral tegmental areaGABA neuronsVTA GABATegmental areaMouse ventral tegmental areaGABA projection neuronsVTA GABAergic neuronsVTA GABA neuronsMagnocellular preoptic nucleusDeep mesencephalic nucleusLocal inhibitory connectionsPrefrontal cortical regionsDrugs of abuseGlutamatergic efferentsSpecific anterogradeBrainstem targetsDorsal rapheNeurons projectGABAergic markersGABAergic neuronsRetrograde tracingProjection neuronsLateral hypothalamusMesencephalic nucleusCentral amygdala
2013
Exploring the Nicotinic Acetylcholine Receptor-Associated Proteome with iTRAQ and Transgenic Mice
McClure-Begley TD, Stone KL, Marks MJ, Grady SR, Colangelo CM, Lindstrom JM, Picciotto MR. Exploring the Nicotinic Acetylcholine Receptor-Associated Proteome with iTRAQ and Transgenic Mice. Genomics Proteomics & Bioinformatics 2013, 11: 207-218. PMID: 23891776, PMCID: PMC3806329, DOI: 10.1016/j.gpb.2013.05.005.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsPutative interacting proteinsΒ2 subunitMammalian central nervous systemAcetylcholine receptorsInteracting proteinProteomic analysisQuantitative proteomicsCytoskeletal rearrangementsIsobaric tagsNeuronal nicotinic acetylcholine receptorsCalcium signalingAbsolute quantitationΑ4β2 nAChRsProteinReduced expressionΒ2 subunit expressionPotential targetCentral nervous systemSubunitsExpressionPrincipal receptorTransgenic miceSubunit expressionΑ4
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
2011
Galanin negatively modulates opiate withdrawal via galanin receptor 1
Holmes FE, Armenaki A, Iismaa TP, Einstein EB, Shine J, Picciotto MR, Wynick D, Zachariou V. Galanin negatively modulates opiate withdrawal via galanin receptor 1. Psychopharmacology 2011, 220: 619-625. PMID: 21969124, PMCID: PMC3324978, DOI: 10.1007/s00213-011-2515-x.Peer-Reviewed Original ResearchConceptsGalanin receptor 1Chronic morphine administrationMorphine administrationLocus coeruleusGalanin expressionOpiate withdrawalReceptor 1Distinct G protein-coupled receptorsPrecipitation of withdrawalAction of morphineDoses of morphineWild-type miceTransgenic mouse lineG protein-coupled receptorsExpress galaninGalanin levelsWild-type controlsProtein-coupled receptorsNeuropeptide galaninMorphine dependenceWithdrawal signsOpiate dependenceGalaninTransgenic miceGalR2 geneAn 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 system
2010
Cortico-Thalamic Connectivity is Vulnerable to Nicotine Exposure During Early Postnatal Development through α4/β2/α5 Nicotinic Acetylcholine Receptors
Heath CJ, King SL, Gotti C, Marks MJ, Picciotto MR. Cortico-Thalamic Connectivity is Vulnerable to Nicotine Exposure During Early Postnatal Development through α4/β2/α5 Nicotinic Acetylcholine Receptors. Neuropsychopharmacology 2010, 35: 2324-2338. PMID: 20736992, PMCID: PMC2955839, DOI: 10.1038/npp.2010.130.Peer-Reviewed Original ResearchConceptsDevelopmental nicotine exposureNicotine exposureNicotinic acetylcholine receptorsAcetylcholine receptorsΑ5 nicotinic acetylcholine receptorConstituents of smokeEarly post-natal periodPrimary addictive componentΑ5 nAChR subunitTobacco smoke exposureCortico-thalamic connectivityPost-natal periodEarly postnatal developmentPassive avoidance behaviorCorticothalamic neuronsAddictive componentCorticothalamic projectionsSmoke exposureReceptor subtypesNAChR subtypesDevelopmental exposureMouse modelNeurodevelopmental periodAnimal modelsBehavioral alterations
2009
Localized low‐level re‐expression of high‐affinity mesolimbic nicotinic acetylcholine receptors restores nicotine‐induced locomotion but not place conditioning
Mineur YS, Brunzell DH, Grady SR, Lindstrom JM, McIntosh JM, Marks MJ, King SL, Picciotto MR. Localized low‐level re‐expression of high‐affinity mesolimbic nicotinic acetylcholine receptors restores nicotine‐induced locomotion but not place conditioning. Genes Brain & Behavior 2009, 8: 257-266. PMID: 19077117, PMCID: PMC2672109, DOI: 10.1111/j.1601-183x.2008.00468.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsConditioning, PsychologicalCyclic AMP Response Element-Binding ProteinDopamineGamma-Aminobutyric AcidGene Expression RegulationLocomotionMiceMice, Inbred C57BLMice, TransgenicNicotineNicotinic AgonistsPhosphorylationPresynaptic TerminalsReceptors, NicotinicRewardSynaptosomesTobacco Use DisorderVentral Tegmental AreaConceptsVentral tegmental areaGamma-aminobutyric acidNicotinic acetylcholine receptorsCyclic AMP response element binding proteinTegmental areaPlace preferenceTransgenic miceAcetylcholine receptorsBeta2 knockout micePedunculopontine tegmental areaSystemic nicotine administrationHigh-affinity nAChRsLaterodorsal tegmental nucleusNicotine place preferenceNicotinic partial agonistPlace preference testingDifferent neuronal subtypesAMP response element binding proteinTotal CREB levelsResponse element-binding proteinDA neuronsCholinergic neuronsNicotine administrationSystemic nicotineSmoking cessation
2008
Regulation of Synaptic Efficacy in Hypocretin/Orexin-Containing Neurons by Melanin Concentrating Hormone in the Lateral Hypothalamus
Rao Y, Lu M, Ge F, Marsh DJ, Qian S, Wang AH, Picciotto MR, Gao XB. Regulation of Synaptic Efficacy in Hypocretin/Orexin-Containing Neurons by Melanin Concentrating Hormone in the Lateral Hypothalamus. Journal Of Neuroscience 2008, 28: 9101-9110. PMID: 18784290, PMCID: PMC2562258, DOI: 10.1523/jneurosci.1766-08.2008.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnalysis of VarianceAnimalsAnimals, NewbornBehavior, AnimalBenzazepinesBenzhydryl CompoundsCentral Nervous System StimulantsDopamine AgonistsDose-Response Relationship, DrugExcitatory Amino Acid AgentsGlutamic AcidGreen Fluorescent ProteinsHypothalamic Area, LateralHypothalamic HormonesIn Vitro TechniquesIntracellular Signaling Peptides and ProteinsMelaninsMiceMice, Inbred C57BLMice, TransgenicModafinilMotor ActivityNeuronsNeuropeptidesOrexinsPertussis ToxinPituitary HormonesReceptors, SomatostatinSynapsesSynaptic TransmissionTime FactorsConceptsHypocretin/orexin neuronsMCHR1 KO miceOrexin-containing neuronsLateral hypothalamusWild-type miceOrexin neuronsHypocretin/orexinKO miceMCH receptor 1Action potential firingEffects of modafinilMelanin-Concentrating HormoneHypocretin/orexin signalingGroups of neuronsMCH neuronsMiniature EPSCsWT miceHypocretin/Glutamatergic synapsesOrexin signalingSynaptic transmissionPertussis toxinBrain areasReciprocal innervationInhibitory influence
2005
Galanin can attenuate opiate reinforcement and withdrawal
Picciotto MR, Hawes JJ, Brunzell DH, Zachariou V. Galanin can attenuate opiate reinforcement and withdrawal. Neuropeptides 2005, 39: 313-315. PMID: 15944028, DOI: 10.1016/j.npep.2004.12.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGalaninHumansMiceMice, KnockoutMice, TransgenicOpioid-Related DisordersSubstance Withdrawal SyndromeConceptsOpiate reinforcementGalanin receptor agonistAction of opiatesUseful therapeutic agentEndogenous galaninReceptor agonistGalaninKnockout miceBrain areasTransgenic miceBrain regionsBehavioral signsOpiate addictionTherapeutic agentsBody of dataAltered susceptibilityWithdrawalMiceReceptorsAgonistsOpiates
2004
Nestin promoter/enhancer directs transgene expression to precursors of adult generated periglomerular neurons
Beech RD, Cleary MA, Treloar HB, Eisch AJ, Harrist AV, Zhong W, Greer CA, Duman RS, Picciotto MR. Nestin promoter/enhancer directs transgene expression to precursors of adult generated periglomerular neurons. The Journal Of Comparative Neurology 2004, 475: 128-141. PMID: 15176089, DOI: 10.1002/cne.20179.Peer-Reviewed Original ResearchConceptsPG neuronsSubventricular zoneGranule cellsOlfactory bulbMajor neurogenic regionsAdult-generated neuronsSVZ precursor cellsTetracycline transactivatorRostral migratory streamOlfactory bulb interneuronsTransgene expressionPeriglomerular neuronsPeriglomerular cellsNestin promoterTyrosine hydroxylaseAdult brainInterneuronal populationsBulb interneuronsNeurogenic regionsMigratory streamNeuronal precursorsNeuronsUnique subsetPromoter/enhancerPrecursor cells
2003
α4β2* Nicotinic Acetylcholine Receptors Modulate the Effects of Ethanol and Nicotine on the Acoustic Startle Response
Owens JC, Balogh SA, McClure‐Begley T, Butt CM, Labarca C, Lester HA, Picciotto MR, Wehner JM, Collins AC. α4β2* Nicotinic Acetylcholine Receptors Modulate the Effects of Ethanol and Nicotine on the Acoustic Startle Response. Alcohol Clinical And Experimental Research 2003, 27: 1867-1875. PMID: 14691373, DOI: 10.1097/01.alc.0000102700.72447.0f.Peer-Reviewed Original ResearchConceptsAcoustic startle responseEffects of ethanolLSxSS RIStartle responseAcoustic startleAlpha4beta2 nAChRsEthanol effectsBeta2 null mutant miceNeuronal nicotinic cholinergic receptorsEthanol-induced depressionNicotinic cholinergic receptorsPotential roleNicotinic acetylcholine receptorsNull mutant miceAlpha4 nAChRsCholinergic receptorsTobacco abuseNicotine effectsT polymorphismAcetylcholine receptorsLSXSS recombinantMutant miceBehavioral effectsNicotineStartleThe neuropeptide galanin modulates behavioral and neurochemical signs of opiate withdrawal
Zachariou V, Brunzell DH, Hawes J, Stedman DR, Bartfai T, Steiner RA, Wynick D, Langel Ü, Picciotto MR. The neuropeptide galanin modulates behavioral and neurochemical signs of opiate withdrawal. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 9028-9033. PMID: 12853567, PMCID: PMC166432, DOI: 10.1073/pnas.1533224100.Peer-Reviewed Original ResearchConceptsMorphine withdrawal signsWithdrawal signsOpiate withdrawalGalanin agonistsEffects of galaninLocus coeruleus neuronsC-Fos immunoreactivityBlood-brain barrierEndogenous galaninMorphine withdrawalNoradrenergic neuronsCoeruleus neuronsC57BL/6 miceNeurochemical signsNeuropeptide galaninLocus coeruleusPossible molecular mechanismsTyrosine hydroxylaseGalaninNeuronal activityGalanin peptidePhysical signsTransgenic miceDrug dependenceBehavioral effectsConditional Expression in Corticothalamic Efferents Reveals a Developmental Role for Nicotinic Acetylcholine Receptors in Modulation of Passive Avoidance Behavior
King SL, Marks MJ, Grady SR, Caldarone BJ, Koren AO, Mukhin AG, Collins AC, Picciotto MR. Conditional Expression in Corticothalamic Efferents Reveals a Developmental Role for Nicotinic Acetylcholine Receptors in Modulation of Passive Avoidance Behavior. Journal Of Neuroscience 2003, 23: 3837-3843. PMID: 12736354, PMCID: PMC6742204, DOI: 10.1523/jneurosci.23-09-03837.2003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAvoidance LearningBehavior, AnimalBinding, CompetitiveCerebral CortexElectroshockGene Expression Regulation, DevelopmentalMiceMice, Inbred C57BLMice, Inbred ICRMice, KnockoutMice, TransgenicNeurons, EfferentNicotineNicotinic AgonistsPresynaptic TerminalsReceptors, NicotinicTetracyclineThalamusTransgenesConceptsPrenatal nicotine exposureNicotinic acetylcholine receptorsPassive avoidanceLines of miceNicotine exposureTransgenic miceAcetylcholine receptorsHigh-affinity nicotinic acetylcholine receptorsTetracycline-regulated transgenic systemHigh-affinity nicotinic receptorsPotential neuroanatomical substratesRubidium efflux assaysHigh-affinity nAChRsEffects of nicotineSpecific neuronal populationsPassive avoidance behaviorAttention deficit hyperactivity disorderWild-type animalsDeficit hyperactivity disorderPresynaptic nAChRsCorticothalamic neuronsSite of actionNicotinic receptorsNeuronal populationsCognitive impairment
1999
Expression of the transcription factor ΔFosB in the brain controls sensitivity to cocaine
Kelz M, Chen J, Carlezon W, Whisler K, Gilden L, Beckmann A, Steffen C, Zhang Y, Marotti L, Self D, Tkatch T, Baranauskas G, Surmeier D, Neve R, Duman R, Picciotto M, Nestler E. Expression of the transcription factor ΔFosB in the brain controls sensitivity to cocaine. Nature 1999, 401: 272-276. PMID: 10499584, DOI: 10.1038/45790.Peer-Reviewed Original ResearchConceptsNucleus accumbensGlutamate receptor subunit GluR2Locomotor-activating effectsFos family transcription factorsTranscription factor ΔFosBDrugs of abuseΔFosB expressionAcute exposureTransgenic miceChronic exposureSubunit GluR2ΔFosBCocaine addictionAccumbensCocainePersistent expressionTranscription factorsSustained accumulationBrainExposureStable isoformSubset of nucleiExpressionGene expressionMorphine