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 ResearchMeSH KeywordsAcetylcholineAnimalsBrainCholinergic AgentsLearningMicrodialysisNeurotransmitter Agents
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 IIHippocampal acetylcholine modulates stress-related behaviors independent of specific cholinergic inputs
Mineur YS, Mose TN, Vanopdenbosch L, Etherington IM, Ogbejesi C, Islam A, Pineda CM, Crouse RB, Zhou W, Thompson DC, Bentham MP, Picciotto MR. Hippocampal acetylcholine modulates stress-related behaviors independent of specific cholinergic inputs. Molecular Psychiatry 2022, 27: 1829-1838. PMID: 34997190, PMCID: PMC9106825, DOI: 10.1038/s41380-021-01404-7.Peer-Reviewed Original ResearchConceptsStress-related behaviorsCholinergic inputMedial septum/diagonal bandBehavioral effectsBrain ACh levelsChAT-positive neuronsSelective chemogenetic activationMuscarinic ACh receptorsDepression-like symptomsSignificant behavioral effectsHippocampal acetylcholineMaladaptive behavioral responsesAntidepressant effectsCholinergic neuronsACh releaseChemogenetic activationChemogenetic inhibitionCholinergic antagonistsLocal infusionAcetylcholine levelsACh levelsDiagonal bandACh receptorsHippocampal neuronsPharmacological approaches
2020
Acetylcholine 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 acquisitionCuesConverging evidence that short-active photoperiod increases acetylcholine signaling in the hippocampus
Cope ZA, Lavadia ML, Joosen AJM, van de Cappelle CJA, Lara JC, Huval A, Kwiatkowski MK, Picciotto MR, Mineur YS, Dulcis D, Young JW. Converging evidence that short-active photoperiod increases acetylcholine signaling in the hippocampus. Cognitive, Affective, & Behavioral Neuroscience 2020, 20: 1173-1183. PMID: 32794101, PMCID: PMC7718303, DOI: 10.3758/s13415-020-00824-2.Peer-Reviewed Original ResearchConceptsSeasonal affective disorderFST immobilityBipolar disorderReduced dopamine transporter expressionHippocampal cholinergic mechanismsNicotinic receptor blockadeDopamine transporter expressionAcetylcholinesterase inhibitor physostigmineSwim test immobilityCholinergic treatmentReceptor blockadeCholinergic mechanismsAcetylcholine neurotransmissionInhibitor physostigmineViral administrationHippocampal expressionACh levelsTest immobilityAffective disordersDepression symptomsSubsequent deficitsHealthy animalsTransporter expressionAcetylcholinePhysostigmineHippocampal 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 miceOrigin and Function of Stress-Induced IL-6 in Murine Models
Qing H, Desrouleaux R, Israni-Winger K, Mineur YS, Fogelman N, Zhang C, Rashed S, Palm NW, Sinha R, Picciotto MR, Perry RJ, Wang A. Origin and Function of Stress-Induced IL-6 in Murine Models. Cell 2020, 182: 372-387.e14. PMID: 32610084, PMCID: PMC7384974, DOI: 10.1016/j.cell.2020.05.054.Peer-Reviewed Original ResearchMeSH KeywordsAdipose Tissue, BrownAnimalsBone Marrow CellsBone Marrow TransplantationBrainChemokinesCytokinesDisease Models, AnimalGluconeogenesisHyperglycemiaInterleukin-6LiverMaleMiceMice, Inbred C57BLMice, KnockoutReceptors, Adrenergic, beta-3Receptors, Interleukin-6Stress, PsychologicalUncoupling Protein 1ConceptsInterleukin-6Subsequent inflammatory challengeAcute psychological stressBrown adipose tissueDominant cytokineImmunometabolic reprogrammingInflammatory challengeEndocrine organMurine modelMouse modelAdipose tissueNeuropsychiatric diseasesAcute stressHepatic gluconeogenesisStress hormonesBrown adipocytesPsychological stressDependent fashionDiseaseInstructive signalsHyperglycemiaInflammationCytokinesMortalityHormoneCumulative Effects of Social Stress on Reward-Guided Actions and Prefrontal Cortical Activity
Barthas F, Hu MY, Siniscalchi MJ, Ali F, Mineur YS, Picciotto MR, Kwan AC. Cumulative Effects of Social Stress on Reward-Guided Actions and Prefrontal Cortical Activity. Biological Psychiatry 2020, 88: 541-553. PMID: 32276717, PMCID: PMC7434704, DOI: 10.1016/j.biopsych.2020.02.008.Peer-Reviewed Original ResearchConceptsPrefrontal cortical activityCortical activityIndividual layer 2/3 pyramidal neuronsLayer 2/3 pyramidal neuronsStress exposureDepressive-like phenotypeTwo-photon calcium imagingSocial stressChronic social stressIndividual prefrontal neuronsMedial prefrontal cortexPyramidal neuronsMotor subregionsNeural dysfunctionResilient miceCalcium imagingPrefrontal neuronsAbnormal levelsPrefrontal cortexSocial defeatDistinct neural responsesStress-induced lossGoal-directed actionsEnsemble activityDefeat sessions
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 levelsEncodingAChVariability in nicotine conditioned place preference and stress‐induced reinstatement in mice: Effects of sex, initial chamber preference, and guanfacine
Lee AM, Calarco CA, McKee SA, Mineur YS, Picciotto MR. Variability in nicotine conditioned place preference and stress‐induced reinstatement in mice: Effects of sex, initial chamber preference, and guanfacine. Genes Brain & Behavior 2019, 19: e12601. PMID: 31364813, PMCID: PMC8045136, DOI: 10.1111/gbb.12601.Peer-Reviewed Original ResearchConceptsStress-induced reinstatementEffects of guanfacinePlace preferenceFemale miceInfralimbic cortexArc immunoreactivityΑ2-adrenergic receptor agonistAnterior insulaNeurobiological mechanismsLateral central amygdalaNovel treatment optionsChamber preferencePlace preference acquisitionSex-dependent changesStress-induced relapseDose-response patternNucleus accumbens coreNicotine-dependent behaviorsSmoking occursTreatment optionsNicotine rewardReceptor agonistCentral amygdalaNeuronal activationPreclinical studies
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 disordersDysfunctionSupercomplexesPhenotypeInteraction 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 mechanismsHippocampal 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 ResearchConceptsDepression-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
CaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory
Park J, Chávez AE, Mineur YS, Morimoto-Tomita M, Lutzu S, Kim KS, Picciotto MR, Castillo PE, Tomita S. CaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory. Neuron 2016, 92: 75-83. PMID: 27667007, PMCID: PMC5059846, DOI: 10.1016/j.neuron.2016.09.002.Peer-Reviewed Original ResearchConceptsCaMKII phosphorylation siteCaMKII substratePhosphorylation sitesDependent protein kinase IIProtein kinase IIReceptor-dependent activationNMDA receptor-dependent activationProtein phosphorylationAMPAR-mediated transmissionKinase IICaMKII-dependent enhancementLong-term potentiationCaMKII phosphorylationCellular mechanismsPhosphorylationMolecular targetsAMPA receptorsCrucial mediatorSynaptic plasticityMemory formationSynaptic insertionEssential stepSynaptic transmissionActivity-dependent strengtheningBasal transmissionAn 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 ResearchComparative mRNA analysis of behavioral and genetic mouse models of aggression
Malki K, Tosto MG, Pain O, Sluyter F, Mineur YS, Crusio WE, de Boer S, Sandnabba KN, Kesserwani J, Robinson E, Schalkwyk LC, Asherson P. Comparative mRNA analysis of behavioral and genetic mouse models of aggression. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2016, 171: 427-436. PMID: 26888158, DOI: 10.1002/ajmg.b.32424.Peer-Reviewed Original ResearchConceptsProbe setsExpression of genesGenetic mouse studiesGene hubsGene networksProtein degradationCandidate genesERG2 geneNetwork analysisGenetic mouse modelsDiscovery-replication designRedox pathwaysGenesP38 MAPKAggression-related traitsMouse modelMouse brain tissueGenetic modelsMRNA studiesMRNA analysisDiscovery studiesDiscovery setPathwayMouse studiesSignificant overlap
2015
Multiple 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 conditionsNicotine