2020
Hippocampal knockdown of α2 nicotinic or M1 muscarinic acetylcholine receptors in C57BL/6J male mice impairs cued fear conditioning
Mineur YS, Ernstsen C, Islam A, Maibom KL, Picciotto MR. Hippocampal knockdown of α2 nicotinic or M1 muscarinic acetylcholine receptors in C57BL/6J male mice impairs cued fear conditioning. Genes Brain & Behavior 2020, 19: e12677. PMID: 32447811, PMCID: PMC8018799, DOI: 10.1111/gbb.12677.Peer-Reviewed Original ResearchConceptsFear learningShort-term learningNumber of paradigmsCued fearLight/dark boxFear conditioningContextual memoryStress-related behaviorsStress-induced reactivityTerm learningBrain circuitsRobust effectM1 mAChRHippocampal acetylcholineM1 muscarinic ACh receptorsNovelty-suppressed feeding testLearningMemoryDark boxHippocampus of malesM1 muscarinic acetylcholine receptorHippocampal knockdownFearMuscarinic ACh receptorsGroups of mice
2019
Induction of reversible bidirectional social approach bias by olfactory conditioning in male mice
Chan J, Stout D, Pittenger ST, Picciotto MR, Lewis AS. Induction of reversible bidirectional social approach bias by olfactory conditioning in male mice. Social Neuroscience 2019, 15: 25-35. PMID: 31303111, PMCID: PMC6980898, DOI: 10.1080/17470919.2019.1644370.Peer-Reviewed Original ResearchConceptsPositive social experiencesSocial avoidanceSocial experienceNegative social experiencesBrief social defeatApproach biasNeural representationApproach behaviorExperience valenceBehavioral paradigmsBehavioral confoundsMost paradigmsNegative conditioningOlfactory conditioningSocial approachSocial defeatBrain regionsSubstantial functional impairmentAvoidanceConditioningParadigmNeuropsychiatric disordersFunctional impairmentExperienceConfoundsPerinatal nicotine exposure impairs learning of a skilled forelimb reaching task in male but not female adult mice
Lee AM, Picciotto MR. Perinatal nicotine exposure impairs learning of a skilled forelimb reaching task in male but not female adult mice. Behavioural Brain Research 2019, 367: 176-180. PMID: 30959127, PMCID: PMC6481625, DOI: 10.1016/j.bbr.2019.04.007.Peer-Reviewed Original ResearchConceptsNicotine exposureSingle-pellet reaching taskMotor tasksCortical synaptic plasticityPerinatal nicotine exposureDevelopmental nicotine exposureGross motor functionNicotine-treated animalsNicotine-induced changesFemale adult miceSkilled motor taskGross motor performanceAdverse outcomesMotor cortexFemale miceMale miceMotor functionSkilled forelimbPreclinical studiesControl animalsAdult miceImpaired learningSynaptic plasticityFemale pupsMorphologic changes
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 disordersDysfunctionSupercomplexesPhenotypeStriatin-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 neuronsInteraction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice
Mineur YS, Cahuzac EL, Mose TN, Bentham MP, Plantenga ME, Thompson DC, Picciotto MR. Interaction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice. Neuropsychopharmacology 2018, 43: 2118-2125. PMID: 29472646, PMCID: PMC6098039, DOI: 10.1038/s41386-018-0024-x.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAdrenergic alpha-AgonistsAlkaloidsAmygdalaAnimalsAnxietyAzocinesCholinesterase InhibitorsDepressionFemaleGene Knockdown TechniquesGuanfacineMaleMiceMice, Inbred C57BLNicotinic AgonistsNorepinephrineParasympathetic Nervous SystemQuinolizinesReceptors, Adrenergic, alpha-2Signal TransductionSympathetic Nervous SystemConceptsAntidepressant-like effectsNoradrenergic systemMale C57BL/6J miceDepression-related behaviorsDepression-like phenotypeNicotinic acetylcholine receptorsAntidepressant efficacyCholinergic interactionsNE terminalsC57BL/6J miceShRNA-mediated knockdownAgonist guanfacineAgonist cytisineClinical studiesSmoking relapseΑ2A receptorsAcute abstinenceBrain areasAcetylcholine receptorsAcetylcholineGuanfacineAmygdalaBehavioral effectsAnxiety disordersStress pathways
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 activityMenthol disrupts nicotine’s psychostimulant properties in an age and sex-dependent manner in C57BL/6J mice
Fait BW, Thompson DC, Mose TN, Jatlow P, Jordt SE, Picciotto MR, Mineur YS. Menthol disrupts nicotine’s psychostimulant properties in an age and sex-dependent manner in C57BL/6J mice. Behavioural Brain Research 2017, 334: 72-77. PMID: 28743602, PMCID: PMC5580257, DOI: 10.1016/j.bbr.2017.07.027.Peer-Reviewed Original ResearchConceptsAdult male miceNicotine intakeMale micePsychostimulant effectsPsychostimulant propertiesHome cage locomotor activitySex-dependent mannerSex-dependent mechanismsBlood levelsAdolescent miceFemale miceLocomotor stimulationLocomotor activityNicotine sensitivityAge groupsE-cigarettesMiceIntakeSignificant decreaseNicotineAgeSexBehavioral changesAdultsSpecific mechanismsAccess to nicotine in drinking water reduces weight gain without changing caloric intake on high fat diet in male C57BL/6J mice
Calarco CA, Lee S, Picciotto MR. Access to nicotine in drinking water reduces weight gain without changing caloric intake on high fat diet in male C57BL/6J mice. Neuropharmacology 2017, 123: 210-220. PMID: 28623168, PMCID: PMC5544033, DOI: 10.1016/j.neuropharm.2017.06.012.Peer-Reviewed Original ResearchConceptsHigh-fat dietCaloric intakeWeight gainFat dietFemale miceMale miceBody weightAdipose tissueEffects of HFDOverall caloric intakeAmphetamine-regulated transcriptNicotinic acetylcholine receptor subunitsLower body weightMelanin-concentrating hormoneSex-dependent mannerRegulation of agoutiChow-fed animalsAcetylcholine receptor subunitsNicotine administrationChronic consumptionArcuate nucleusNicotine dosesNicotine intakeFood intakeTobacco useHippocampal α7 nicotinic ACh receptors contribute to modulation of depression‐like behaviour in C57BL/6J mice
Mineur YS, Mose TN, Blakeman S, Picciotto MR. Hippocampal α7 nicotinic ACh receptors contribute to modulation of depression‐like behaviour in C57BL/6J mice. British Journal Of Pharmacology 2017, 175: 1903-1914. PMID: 28264149, PMCID: PMC5979617, DOI: 10.1111/bph.13769.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAnimalsBehavior, AnimalDepressionFemaleHippocampusMaleMiceMice, Inbred C57BLPhysostigmineConceptsDepression-like behaviorNicotinic ACh receptorsFemale miceMale miceCholinergic signalingACh receptorsΑ7 nAChRsSignificant antidepressant-like effectΑ7 nicotinic ACh receptorsEffect of α7Antidepressant-like effectsAgonist GTS-21Depression-related behaviorsC-Fos immunoreactivityACh receptor antagonistDepression-like phenotypeAnxiety-like behaviorNicotinic acetylcholine receptorsAnxiety-like phenotypeHippocampal α7Physostigmine administrationAntagonist methyllycaconitineReceptor antagonistSwim testGTS-21
2016
Menthol decreases oral nicotine aversion in C57BL/6 mice through a TRPM8-dependent mechanism
Fan L, Balakrishna S, Jabba SV, Bonner PE, Taylor SR, Picciotto MR, Jordt SE. Menthol decreases oral nicotine aversion in C57BL/6 mice through a TRPM8-dependent mechanism. Tobacco Control 2016, 25: ii50. PMID: 27698211, PMCID: PMC5496986, DOI: 10.1136/tobaccocontrol-2016-053209.Peer-Reviewed Original ResearchConceptsSmokeless tobacco productsWild-type miceOral nicotineC57BL/6 miceTobacco productsNicotine aversionAversive effectsTwo-bottle choice drinkingTrigeminal sensory neuronsEffect of mentholProduct useMenthol concentrationOral mentholSensory neuronsAversive concentrationsMenthol receptorOral cavityMenthol effectsRespiratory irritationMiceNicotineTRPM8Oral irritantsIrritantsAversive tasteGABA 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 antagonistAn epigenetic mechanism mediates developmental nicotine effects on neuronal structure and behavior
Jung Y, Hsieh LS, Lee AM, Zhou Z, Coman D, Heath CJ, Hyder F, Mineur YS, Yuan Q, Goldman D, Bordey A, Picciotto MR. An epigenetic mechanism mediates developmental nicotine effects on neuronal structure and behavior. Nature Neuroscience 2016, 19: 905-914. PMID: 27239938, PMCID: PMC4925298, DOI: 10.1038/nn.4315.Peer-Reviewed Original Research
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 exposurePathwayInteractionFilamentsEnrichmentMultiple Nicotinic Acetylcholine Receptor Subtypes in the Mouse Amygdala Regulate Affective Behaviors and Response to Social Stress
Mineur YS, Fote GM, Blakeman S, Cahuzac EL, Newbold SA, Picciotto MR. Multiple Nicotinic Acetylcholine Receptor Subtypes in the Mouse Amygdala Regulate Affective Behaviors and Response to Social Stress. Neuropsychopharmacology 2015, 41: 1579-1587. PMID: 26471256, PMCID: PMC4832019, DOI: 10.1038/npp.2015.316.Peer-Reviewed Original ResearchConceptsDepression-like behaviorBasolateral amygdalaΑ7 nAChRsCholinergic signalingMultiple nicotinic acetylcholine receptor subtypesNon-selective nAChR antagonist mecamylamineNicotinic acetylcholine receptor activityNicotinic acetylcholine receptor subtypesStress-mediated behaviorsAntidepressant-like effectsAcetylcholine receptor activityC-Fos immunoreactivityNAChR antagonist mecamylamineAcetylcholine receptor subtypesEffects of nicotineMajor depressive disorderSocial defeat stressAnxiety-like behaviorPre-clinical studiesHuman clinical trialsModels of anxietyMouse behavioral modelsHypercholinergic stateAntagonist mecamylamineLocal infusionModulation of aggressive behavior in mice by nicotinic receptor subtypes
Lewis AS, Mineur YS, Smith PH, Cahuzac EL, Picciotto MR. Modulation of aggressive behavior in mice by nicotinic receptor subtypes. Biochemical Pharmacology 2015, 97: 488-497. PMID: 26212554, PMCID: PMC4600457, DOI: 10.1016/j.bcp.2015.07.019.Peer-Reviewed Original ResearchConceptsAcute nicotine administrationNicotine administrationHypolocomotor effectNicotinic acetylcholine receptor agonist nicotineAgonist GTS-21Nicotinic receptor subtypesAnti-aggressive propertiesDihydro-β-erythroidineBALB/cNeurobiology of aggressionSocial interaction timeCurrent pharmacotherapyAntagonist methyllycaconitineC57BL/6 miceWorse outcomesGTS-21Receptor subtypesPathological aggressionAgonist nicotineΑ7 nAChRsSpecific treatmentSide effectsPharmacological studiesNeuropsychiatric conditionsNicotineAntidepressant-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
Expression of the 5-HT1A Serotonin Receptor in the Hippocampus Is Required for Social Stress Resilience and the Antidepressant-Like Effects Induced by the Nicotinic Partial Agonist Cytisine
Mineur YS, Einstein EB, Bentham MP, Wigestrand MB, Blakeman S, Newbold SA, Picciotto MR. Expression of the 5-HT1A Serotonin Receptor in the Hippocampus Is Required for Social Stress Resilience and the Antidepressant-Like Effects Induced by the Nicotinic Partial Agonist Cytisine. Neuropsychopharmacology 2014, 40: 938-946. PMID: 25288485, PMCID: PMC4330507, DOI: 10.1038/npp.2014.269.Peer-Reviewed Original ResearchMeSH Keywords8-Hydroxy-2-(di-n-propylamino)tetralinAlkaloidsAnimalsAntidepressive AgentsAzocinesDisease Models, AnimalDrug SynergismFluoxetineGene Expression RegulationHEK293 CellsHindlimb SuspensionHippocampusHumansInterpersonal RelationsMaleMiceMice, Inbred C57BLMotor ActivityQuinolizinesReceptor, Serotonin, 5-HT1ASelective Serotonin Reuptake InhibitorsSerotonin Receptor AgonistsStress, PsychologicalConceptsAntidepressant-like effectsSelective serotonin reuptake inhibitorsDorsal rapheCholinergic systemAgonist cytisineNicotinic acetylcholine receptor blockersEffects of cytisineTreatment-resistant patientsSerotonin reuptake inhibitorsAcetylcholine receptor blockerSSRI fluoxetineReceptor blockersAntidepressant efficacyReuptake inhibitorsSerotonin depletionCholinergic drugsMood disordersSerotonin receptorsMouse modelPharmacological approachesHippocampusReceptorsCytisineRapheMolecular mechanismsGABAergic 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 amygdalaSelf-Administration of Ethanol, Cocaine, or Nicotine Does Not Decrease the Soma Size of Ventral Tegmental Area Dopamine Neurons
Mazei-Robison MS, Appasani R, Edwards S, Wee S, Taylor SR, Picciotto MR, Koob GF, Nestler EJ. Self-Administration of Ethanol, Cocaine, or Nicotine Does Not Decrease the Soma Size of Ventral Tegmental Area Dopamine Neurons. PLOS ONE 2014, 9: e95962. PMID: 24755634, PMCID: PMC3995955, DOI: 10.1371/journal.pone.0095962.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell SizeCocaineDopaminergic NeuronsEthanolMaleMice, Inbred C57BLNicotineRats, WistarSelf AdministrationVentral Tegmental AreaConceptsVentral tegmental areaSoma sizeDopamine neuronsVentral tegmental area dopamine neuronsChronic opiate administrationAdditional drug classesDrug-specific mannerMorphological changesSelf-administer cocaineOpiate administrationTegmental areaDrug classesDA circuitsMesolimbic DA circuitSelf-AdministrationFiring rateSimilar morphological changesGeneral hallmarkNeuronsNicotineCocaineDrugsRecent findingsPrevious observationsNeuroplasticity