2023
How can I measure brain acetylcholine levels in vivo? Advantages and caveats of commonly used approaches
Mineur Y, Picciotto M. How can I measure brain acetylcholine levels in vivo? Advantages and caveats of commonly used approaches. Journal Of Neurochemistry 2023, 167: 3-15. PMID: 37621094, PMCID: PMC10616967, DOI: 10.1111/jnc.15943.Peer-Reviewed Original Research
2021
microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity
Horie T, Nakao T, Miyasaka Y, Nishino T, Matsumura S, Nakazeki F, Ide Y, Kimura M, Tsuji S, Rodriguez RR, Watanabe T, Yamasaki T, Xu S, Otani C, Miyagawa S, Matsushita K, Sowa N, Omori A, Tanaka J, Nishimura C, Nishiga M, Kuwabara Y, Baba O, Watanabe S, Nishi H, Nakashima Y, Picciotto MR, Inoue H, Watanabe D, Nakamura K, Sasaki T, Kimura T, Ono K. microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity. Nature Communications 2021, 12: 843. PMID: 33594062, PMCID: PMC7886914, DOI: 10.1038/s41467-021-21107-5.Peer-Reviewed Original ResearchConceptsSympathetic nerve activityAdaptive thermogenesisNerve activityCre miceMiR-33Brown adipose tissue thermogenesisDBH-positive neuronsMiR-33 levelsGABAergic inhibitory neurotransmissionSympathetic nerve toneCentral neural circuitsAdipose tissue thermogenesisGamma-aminobutyric acidDBH-positive cellsMiR-33 deficiencyWhole-body metabolismCold-induced thermogenesisInhibitory neurotransmissionBAT thermogenesisTissue thermogenesisReceptor subunit genesNeural circuitsAdaptive defense mechanismsThermogenesisMice
2019
The role of acetylcholine in negative encoding bias: Too much of a good thing?
Mineur YS, Picciotto MR. The role of acetylcholine in negative encoding bias: Too much of a good thing? European Journal Of Neuroscience 2019, 53: 114-125. PMID: 31821620, PMCID: PMC7282966, DOI: 10.1111/ejn.14641.Peer-Reviewed Original ResearchConceptsPotential neural pathwaysSymptoms of anxietyAffective processesSustained attentionStressful eventsCore symptomsFacilitate learningAppropriate learningNeural pathwaysRole of acetylcholineGood thingLevels of AChLearningDepressionBiasDepressive episodeNeuromodulatory roleCholinergic signalingAnimal studiesAnxietyMemoryAcetylcholine SignalingHigh levelsEncodingACh
2018
The 7q11.23 Protein DNAJC30 Interacts with ATP Synthase and Links Mitochondria to Brain Development
Tebbenkamp ATN, Varela L, Choi J, Paredes MI, Giani AM, Song JE, Sestan-Pesa M, Franjic D, Sousa AMM, Liu ZW, Li M, Bichsel C, Koch M, Szigeti-Buck K, Liu F, Li Z, Kawasawa YI, Paspalas CD, Mineur YS, Prontera P, Merla G, Picciotto MR, Arnsten AFT, Horvath TL, Sestan N. The 7q11.23 Protein DNAJC30 Interacts with ATP Synthase and Links Mitochondria to Brain Development. Cell 2018, 175: 1088-1104.e23. PMID: 30318146, PMCID: PMC6459420, DOI: 10.1016/j.cell.2018.09.014.Peer-Reviewed Original ResearchConceptsCopy number variationsATP synthase dimersOxidative phosphorylation supercomplexesHuman neurodevelopmental disordersATP synthaseWS pathogenesisGene contributionMitochondrial featuresBrain developmentWilliams syndromeMitochondrial dysfunctionNeocortical pyramidal neuronsNeural phenotypesMitochondriaPyramidal neuronsMachineryMorphological featuresNeurodevelopmental disordersDysfunctionSupercomplexesPhenotype
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 exposurePathwayInteractionFilamentsEnrichmentAntidepressant-like effects of guanfacine and sex-specific differences in effects on c-fos immunoreactivity and paired-pulse ratio in male and female mice
Mineur YS, Bentham MP, Zhou WL, Plantenga ME, McKee SA, Picciotto MR. Antidepressant-like effects of guanfacine and sex-specific differences in effects on c-fos immunoreactivity and paired-pulse ratio in male and female mice. Psychopharmacology 2015, 232: 3539-3549. PMID: 26146014, PMCID: PMC4561580, DOI: 10.1007/s00213-015-4001-3.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsPaired-pulse ratioC-Fos immunoreactivityPrefrontal cortexSwim testBrain areasRobust antidepressant-like effectsBrain regionsSex differencesMale C57BL/6J miceDepression-like behaviorEffects of guanfacineAcetylcholinesterase inhibitor physostigmineLight/dark boxBaseline sex differencesC-fos expressionDepression-like stateCritical brain regionsDifferent brain areasSex-specific changesAntidepressant efficacyCholinergic controlInhibitor physostigmineC57BL/6J miceAgonist guanfacine
2014
Neuromodulation by acetylcholine: examples from schizophrenia and depression
Higley MJ, Picciotto MR. Neuromodulation by acetylcholine: examples from schizophrenia and depression. Current Opinion In Neurobiology 2014, 29: 88-95. PMID: 24983212, PMCID: PMC4268065, DOI: 10.1016/j.conb.2014.06.004.Peer-Reviewed Original ResearchHomozygous loss of DIAPH1 is a novel cause of microcephaly in humans
Ercan-Sencicek AG, Jambi S, Franjic D, Nishimura S, Li M, El-Fishawy P, Morgan TM, Sanders SJ, Bilguvar K, Suri M, Johnson MH, Gupta AR, Yuksel Z, Mane S, Grigorenko E, Picciotto M, Alberts AS, Gunel M, Šestan N, State MW. Homozygous loss of DIAPH1 is a novel cause of microcephaly in humans. European Journal Of Human Genetics 2014, 23: 165-172. PMID: 24781755, PMCID: PMC4297910, DOI: 10.1038/ejhg.2014.82.Peer-Reviewed Original ResearchConceptsCell divisionFamily-based linkage analysisLinkage analysisRho effector proteinsLinear actin filamentsMaintenance of polarityMitotic cell divisionHigh-throughput sequencingRare genetic variantsHuman neuronal precursor cellsParametric multipoint linkage analysisActivation of GTPNeuronal precursor cellsFormin familyMammalian DiaphanousEffector proteinsMultipoint linkage analysisSpindle formationActin filamentsNonsense alterationWhole-exome sequencingHuman pathologiesNeuroepithelial cellsGenetic variantsHomozygous loss
2013
In Vivo Evidence for β2 Nicotinic Acetylcholine Receptor Subunit Upregulation in Smokers as Compared With Nonsmokers With Schizophrenia
Esterlis I, Ranganathan M, Bois F, Pittman B, Picciotto MR, Shearer L, Anticevic A, Carlson J, Niciu MJ, Cosgrove KP, D’Souza D. In Vivo Evidence for β2 Nicotinic Acetylcholine Receptor Subunit Upregulation in Smokers as Compared With Nonsmokers With Schizophrenia. Biological Psychiatry 2013, 76: 495-502. PMID: 24360979, PMCID: PMC4019710, DOI: 10.1016/j.biopsych.2013.11.001.Peer-Reviewed Original ResearchConceptsLower β2Negative symptomsCortical regionsLower receptor availabilitySelf-medicate symptomsComparison groupLower negative symptomsHigh β2Executive controlExecutive functionNicotine cravingSex-matched comparison subjectsMood assessmentBrain regionsWorse performanceComparison subjectsDiagnosis interactionLimited brain regionsNicotinic acetylcholine receptorsSchizophreniaSingle photon emissionNAChR availabilityActive smokingTobacco smokingPoor outcomeDifferential Modulation of Brain Nicotinic Acetylcholine Receptor Function by Cytisine, Varenicline, and Two Novel Bispidine Compounds: Emergent Properties of a Hybrid Molecule
Peng C, Stokes C, Mineur YS, Picciotto MR, Tian C, Eibl C, Tomassoli I, Guendisch D, Papke RL. Differential Modulation of Brain Nicotinic Acetylcholine Receptor Function by Cytisine, Varenicline, and Two Novel Bispidine Compounds: Emergent Properties of a Hybrid Molecule. Journal Of Pharmacology And Experimental Therapeutics 2013, 347: 424-437. PMID: 23959137, PMCID: PMC3807070, DOI: 10.1124/jpet.113.206904.Peer-Reviewed Original ResearchMeSH KeywordsAlkaloidsAnimalsAzocinesBehavior, AnimalBenzazepinesBrainBridged Bicyclo Compounds, HeterocyclicDose-Response Relationship, DrugDrug Partial AgonismHEK293 CellsHumansMaleMembrane PotentialsMiceMolecular StructureNicotinic AgonistsOocytesPatch-Clamp TechniquesQuinolizinesQuinoxalinesRatsRats, Sprague-DawleyReceptors, NicotinicTobacco Use DisorderVareniclineXenopus laevisConceptsPartial agonistLGN neuronsMouse tail suspension testLateral geniculate nucleus neuronsNicotinic acetylcholine receptor functionPartial agonist therapiesTail suspension testStratum radiatum interneuronsSmoking cessation drugNicotinic partial agonistAcetylcholine receptor functionHuman embryonic kidney 293 cellsSteady-state activationAgonist therapyRadiatum interneuronsEmbryonic kidney 293 cellsCessation drugsNucleus neuronsSuspension testΑ7 currentsNicotine addictionSide effectsVareniclineΑ4β2 nAChRsSR interneuronsExploring 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 expressionΑ4Molecules and circuits involved in nicotine addiction: The many faces of smoking
Picciotto MR, Mineur YS. Molecules and circuits involved in nicotine addiction: The many faces of smoking. Neuropharmacology 2013, 76: 545-553. PMID: 23632083, PMCID: PMC3772953, DOI: 10.1016/j.neuropharm.2013.04.028.Peer-Reviewed Original ResearchConceptsTobacco smokingNicotine reinforcementTobacco smokeNicotine addictionMultiple brain circuitsSymptoms of anxietyFuture therapeutic developmentSmoking cessationNicotine receptorsAdult smokingDevelopmental exposureSmokingNew treatmentsBrain circuitsTherapeutic developmentCellular basisWidespread addictionCircuit basisCessationBiological basisAddictionBehavioral studiesNumber of behaviorsSmokeVareniclineHigh-affinity nicotinic acetylcholine receptor expression and trafficking abnormalities in psychiatric illness
Lewis AS, Picciotto MR. High-affinity nicotinic acetylcholine receptor expression and trafficking abnormalities in psychiatric illness. Psychopharmacology 2013, 229: 477-485. PMID: 23624811, PMCID: PMC3766461, DOI: 10.1007/s00213-013-3126-5.Peer-Reviewed Original ResearchConceptsPsychiatric illnessNicotinic acetylcholine receptor expressionPre-clinical animal modelsMultiple psychiatric illnessesChronic nicotine exposureHigh-affinity nAChRsAcetylcholine receptor expressionNicotinic receptor subtypesNovel therapeutic agentsHuman psychiatric illnessCholinergic dysfunctionClinical featuresNicotine exposurePatient populationCholinergic systemNicotine intakeReceptor expressionReceptor subtypesMood disordersTobacco usePharmacological agentsAnimal modelsPsychiatric diseasesAcetylcholine receptorsIllness
2012
Imaging Changes in Synaptic Acetylcholine Availability in Living Human Subjects
Esterlis I, Hannestad JO, Bois F, Sewell RA, Tyndale RF, Seibyl JP, Picciotto MR, Laruelle M, Carson RE, Cosgrove KP. Imaging Changes in Synaptic Acetylcholine Availability in Living Human Subjects. Journal Of Nuclear Medicine 2012, 54: 78-82. PMID: 23160789, PMCID: PMC3703589, DOI: 10.2967/jnumed.112.111922.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptor availabilityEndogenous neurotransmitter acetylcholineNicotinic acetylcholine receptorsPhysostigmine administrationAcetylcholine availabilityExtracellular acetylcholineBaseline scanHealthy subjectsReceptor availabilityExtracellular levelsAcetylcholine receptorsMolecular neuroimagingSPECT studiesAcetylcholineNonhuman primatesTissue concentrationsNeurotransmitter acetylcholineHuman subjectsSignificant reductionAdditional scansScansParent concentrationsSubjectsVivo estimationIAMolecular Mechanisms Underlying Behaviors Related to Nicotine Addiction
Picciotto MR, Kenny PJ. Molecular Mechanisms Underlying Behaviors Related to Nicotine Addiction. Cold Spring Harbor Perspectives In Medicine 2012, 3: a012112. PMID: 23143843, PMCID: PMC3530035, DOI: 10.1101/cshperspect.a012112.Peer-Reviewed Original ResearchConceptsMembrane-spanning subunitsLigand-gated ion channelsTobacco smokingLung cancerTobacco dependenceNicotine addictionCHRNB4 gene clusterExpression of α5Neuronal nicotinic acetylcholine receptorsGene clusterSmoking-associated diseasesGenetic variationTobacco smoking habitsEffects of nicotineMolecular mechanismsΑ-subunitProperties of nicotineΒ-subunitNicotinic acetylcholine receptorsSubunitsIon channelsSmoking habitsRecent insightsΒ4 subunitΒ2 subunitThe drive to eat: comparisons and distinctions between mechanisms of food reward and drug addiction
DiLeone RJ, Taylor JR, Picciotto MR. The drive to eat: comparisons and distinctions between mechanisms of food reward and drug addiction. Nature Neuroscience 2012, 15: 1330-1335. PMID: 23007187, PMCID: PMC3570269, DOI: 10.1038/nn.3202.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsPersistent β2*-Nicotinic Acetylcholinergic Receptor Dysfunction in Major Depressive Disorder
Saricicek A, Esterlis I, Maloney KH, Mineur YS, Ruf BM, Muralidharan A, Chen JI, Cosgrove KP, Kerestes R, Ghose S, Tamminga CA, Pittman B, Bois F, Tamagnan G, Seibyl J, Picciotto MR, Staley JK, Bhagwagar Z. Persistent β2*-Nicotinic Acetylcholinergic Receptor Dysfunction in Major Depressive Disorder. American Journal Of Psychiatry 2012, 169: 851-859. PMID: 22772158, PMCID: PMC3494404, DOI: 10.1176/appi.ajp.2012.11101546.Peer-Reviewed Original ResearchConceptsMajor depressive disorderNAChR availabilityDepressed patientsComparison subjectsDepressed subjectsDepressive disorderReceptor availabilityAge-matched comparison subjectsLower receptor availabilityEarly-onset depressionPostmortem brain samplesDopamine receptor availabilityNicotinic acetylcholine receptorsSingle photon emissionPost-mortem samplesEndogenous acetylcholinePrefrontal cortex samplesReceptor dysfunctionDepressive episodePostmortem studiesTrauma ScoreIll subjectsSPECT ligandHealthy subjectsSPECT scansSex Differences in Availability of β2*-Nicotinic Acetylcholine Receptors in Recently Abstinent Tobacco Smokers
Cosgrove KP, Esterlis I, McKee SA, Bois F, Seibyl JP, Mazure CM, Krishnan-Sarin S, Staley JK, Picciotto MR, O’Malley S. Sex Differences in Availability of β2*-Nicotinic Acetylcholine Receptors in Recently Abstinent Tobacco Smokers. JAMA Psychiatry 2012, 69: 418-427. PMID: 22474108, PMCID: PMC3508698, DOI: 10.1001/archgenpsychiatry.2011.1465.Peer-Reviewed Original ResearchMeSH KeywordsAdultAzetidinesBehavior, AddictiveBrainDepressionEstradiolFemaleFunctional NeuroimagingHumansIodine RadioisotopesMaleNicotinic AntagonistsProgesteronePyridinesRadioligand AssayReceptors, NicotinicSex CharacteristicsSmokingSubstance Withdrawal SyndromeTomography, Emission-Computed, Single-PhotonConceptsNAChR availabilityFemale smokersTobacco smokersNicotinic acetylcholine receptorsFemale nonsmokersProgesterone levelsAcetylcholine receptorsFemale sex steroid hormonesSex differencesSex steroid hormone levelsAbstinent tobacco smokersSex-matched nonsmokersTobacco smoking effectsMagnetic resonance imaging studyAge-matched malesEquilibrium distribution volumeEffects of nicotineSex steroid hormonesSteroid hormone levelsUnderlying neurochemical mechanismsResonance imaging studySingle photon emissionDays of abstinenceIA SPECTNicotine therapy
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 geneFACS 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 antibodiesBrainTissueGenes