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 expressionAcetylcholinePhysostigmine
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
Interaction 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
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 ResearchMeSH KeywordsAcetylcholineAnxietyAttentionBipolar DisorderBrainHumansNeural PathwaysNeuroimagingSchizophrenia
2013
Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex
Yang Y, Paspalas CD, Jin LE, Picciotto MR, Arnsten AF, Wang M. Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 12078-12083. PMID: 23818597, PMCID: PMC3718126, DOI: 10.1073/pnas.1307849110.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAconitineAlpha7 Nicotinic Acetylcholine ReceptorAnalysis of VarianceAnimalsBridged Bicyclo Compounds, HeterocyclicCholinergic AgonistsCholinergic AntagonistsCognitionFemaleIontophoresisMacaca mulattaMaleMecamylamineMicroscopy, ImmunoelectronN-MethylaspartatePhenolsPiperidinesPrefrontal CortexQuinuclidinesReceptors, NicotinicSpatial BehaviorSynapsesVisual PerceptionConceptsDorsolateral prefrontal cortexΑ7 nAChRsPrefrontal cortexΑ7 nicotinic acetylcholine receptorGlutamatergic NMDA receptorsCognitive circuitsNicotinic α7 receptorsPrimary visual cortexNMDA receptor actionGenetic insultsNicotinic acetylcholine receptorsDlPFC circuitsPrimate dlPFCACh depletionNMDA actionNMDA receptorsPyramidal cellsΑ7 receptorsNeuronal firingNAChR blockadeAcetylcholine receptorsVisual cortexPersistent firingCognitive functionLow-dose stimulationMorphine dependence and withdrawal induced changes in cholinergic signaling
Neugebauer NM, Einstein EB, Lopez MB, McClure-Begley TD, Mineur YS, Picciotto MR. Morphine dependence and withdrawal induced changes in cholinergic signaling. Pharmacology Biochemistry And Behavior 2013, 109: 77-83. PMID: 23651795, PMCID: PMC3690589, DOI: 10.1016/j.pbb.2013.04.015.Peer-Reviewed Original ResearchConceptsMedial habenulaMorphine dependenceCholinergic signalingInterpeduncular nucleusHigh-affinity nicotinic acetylcholine receptorsNicotinic acetylcholine receptor levelsEffects of cholinergicMorphine-dependent miceChronic morphine administrationAcetylcholine receptor levelsC-fos expressionC-Fos activationNicotinic acetylcholine receptorsDependent miceMorphine administrationMorphine withdrawalCholinergic drugsOpiate withdrawalCholinergic systemEpibatidine bindingReceptor levelsSomatic signsNeuronal activityAcetylcholine receptorsNAChR receptor
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 estimationIAAcetylcholine 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 functionResponseCholinergic
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 excitation
2010
Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis
Mineur YS, Picciotto MR. Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis. Trends In Pharmacological Sciences 2010, 31: 580-586. PMID: 20965579, PMCID: PMC2991594, DOI: 10.1016/j.tips.2010.09.004.Peer-Reviewed Original ResearchConceptsEffects of nicotineDepressive symptomsNeuronal nAChRsNovel antidepressant medicationsDepression-like behaviorMajor depressive disorderNicotinic acetylcholine receptorsAntidepressant medicationNicotine receptorsCholinergic systemDepressive disorderCholinergic hypothesisPreclinical studiesNicotinic drugsPharmacological agentsNicotinic agentsAcetylcholine receptorsEndogenous neurotransmittersSymptomsNAChRsNicotineSmokingDepressed individualsAcetylcholineReceptors
2008
Galanin – 25 years with a multitalented neuropeptide
Picciotto MR. Galanin – 25 years with a multitalented neuropeptide. Cellular And Molecular Life Sciences 2008, 65: 1872-1879. PMID: 18500649, PMCID: PMC11131873, DOI: 10.1007/s00018-008-8151-x.Peer-Reviewed Original ResearchConceptsGalanin receptorsFood intakeOpiate rewardDrug rewardGalanin – 25 yearsAbility of neuropeptidesMesolimbic dopamine systemDrugs of abuseGalanin agonistsNoradrenergic neuronsDrug withdrawalStriatal slicesWithdrawal signsAnalgesic propertiesLocus coeruleusHypothalamic functionDopamine releaseDopamine systemGalaninNovel treatmentsPlace preferenceStress-related pathwaysFiring ratePotential targetWithdrawal
2002
Characterization of [125I]epibatidine binding and nicotinic agonist‐mediated 86Rb+ efflux in interpeduncular nucleus and inferior colliculus of β2 null mutant mice
Marks MJ, Whiteaker P, Grady SR, Picciotto MR, McIntosh JM, Collins AC. Characterization of [125I]epibatidine binding and nicotinic agonist‐mediated 86Rb+ efflux in interpeduncular nucleus and inferior colliculus of β2 null mutant mice. Journal Of Neurochemistry 2002, 81: 1102-1115. PMID: 12065623, DOI: 10.1046/j.1471-4159.2002.00910.x.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAlkaloidsAnimalsAzocinesBinding, CompetitiveBridged Bicyclo Compounds, HeterocyclicDose-Response Relationship, DrugInferior ColliculiIodine RadioisotopesMesencephalonMiceMice, Mutant StrainsNicotinic AgonistsNicotinic AntagonistsPyridinesQuinolizinesReceptors, NicotinicRubidium RadioisotopesTritiumConceptsInterpeduncular nucleusInferior colliculusBrain regionsAccessory olfactory nucleusNull mutant miceOlfactory nucleusNicotinic antagonistsD-tubocurarineMedial habenulaSelective antagonistNicotinic agonistsSuperior colliculusMouse brainAgonistsColliculusMutant micePotent agonistSimilar potencyAntagonistNicotinic activityEfflux
2001
Nicotine Receptor Inactivation Decreases Sensitivity to Cocaine
Zachariou V, Caldarone B, Weathers-Lowin A, George T, Elsworth J, Roth R, Changeux J, Picciotto M. Nicotine Receptor Inactivation Decreases Sensitivity to Cocaine. Neuropsychopharmacology 2001, 24: 576-589. PMID: 11282258, DOI: 10.1016/s0893-133x(00)00224-4.Peer-Reviewed Original ResearchConceptsPlace preferenceDA turnoverLow doseHigh-affinity nicotinic acetylcholine receptorsMesolimbic DA systemHigh-affinity nAChRsNicotinic antagonist mecamylamineWild-type miceMesolimbic dopamine systemFos-related antigensProperties of nicotineCocaine place preferenceΒ2 subunitNicotinic acetylcholine receptorsAntagonist mecamylamineDA releaseMetabolite DOPACNeurochemical changesSubthreshold doseType miceDopamine systemPsychomotor stimulantsAcetylcholine receptorsHigh dosesBrain regionsNicotinic agonists stimulate acetylcholine release from mouse interpeduncular nucleus: a function mediated by a different nAChR than dopamine release from striatum
Grady S, Meinerz N, Cao J, Reynolds A, Picciotto M, Changeux J, McIntosh J, Marks M, Collins A. Nicotinic agonists stimulate acetylcholine release from mouse interpeduncular nucleus: a function mediated by a different nAChR than dopamine release from striatum. Journal Of Neurochemistry 2001, 76: 258-268. PMID: 11145999, DOI: 10.1046/j.1471-4159.2001.00019.x.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAlkaloidsAnimalsAzocinesCalciumCholineConotoxinsCorpus StriatumDopamineDose-Response Relationship, DrugFemaleHeterozygoteHomozygoteMaleMesencephalonMiceMice, Inbred C57BLMice, Mutant StrainsNicotinic AgonistsNicotinic AntagonistsPresynaptic TerminalsProtein SubunitsQuinolizinesReceptors, NicotinicSynaptosomesConceptsAgonist-stimulated releaseAcetylcholine releaseInterpeduncular nucleusStriatal synaptosomesDopamine releaseNicotinic agonistsAlpha-conotoxin MIIMouse striatal synaptosomesAlpha-conotoxin AuIBNicotinic acetylcholine receptorsDose-response curveAcetylcholine receptorsExternal calciumDifferent nAChRsDesensitization ratePersistent phaseAgonistsL nicotineSynaptosomesNull mutationSimilar decreaseInhibition curvesMiceReleaseAcetylcholine
1999
Two pharmacologically distinct components of nicotinic receptor-mediated rubidium efflux in mouse brain require the beta2 subunit.
Marks MJ, Whiteaker P, Calcaterra J, Stitzel JA, Bullock AE, Grady SR, Picciotto MR, Changeux JP, Collins AC. Two pharmacologically distinct components of nicotinic receptor-mediated rubidium efflux in mouse brain require the beta2 subunit. Journal Of Pharmacology And Experimental Therapeutics 1999, 289: 1090-103. PMID: 10215692.Peer-Reviewed Original ResearchConceptsBeta2 subunitBeta2 null mutant miceConcentration-effect curvesMouse brain synaptosomesAlpha4beta2 receptorsBrain synaptosomesNicotinic agonistsMouse brainRubidium effluxMutant miceLine radioactivity detectionDHbetaEAgonistsEffluxBrainStimulationRadioactivity detectionPotencyHexamethoniumErythroidineResponseAcetylcholineMethyllycaconitineAntagonistBungarotoxin
1998
Acetylcholine receptors containing the β2 subunit are involved in the reinforcing properties of nicotine
Picciotto M, Zoli M, Rimondini R, Léna C, Marubio L, Pich E, Fuxe K, Changeux J. Acetylcholine receptors containing the β2 subunit are involved in the reinforcing properties of nicotine. Nature 1998, 391: 173-177. PMID: 9428762, DOI: 10.1038/34413.Peer-Reviewed Original ResearchMeSH Keywords3,4-Dihydroxyphenylacetic AcidAcetylcholineAnimalsBinding SitesCarrier ProteinsCocaineConditioning, OperantDopamineDopamine Plasma Membrane Transport ProteinsHomovanillic AcidIn Vitro TechniquesMaleMembrane GlycoproteinsMembrane Transport ProteinsMiceMice, Inbred C57BLMice, Inbred DBAMice, KnockoutMicrodialysisMotor ActivityNerve Tissue ProteinsNicotineNucleus AccumbensPatch-Clamp TechniquesReceptors, NicotinicSecond Messenger SystemsSubstantia NigraVentral Tegmental AreaConceptsProperties of nicotineAcetylcholine receptorsVentral striatumΒ2 subunitNeuronal nicotinic acetylcholine receptorsMesencephalic dopaminergic neuronsEffects of nicotineWild-type micePatch-clamp recordingsMesolimbic dopamine systemNicotinic acetylcholine receptorsDrugs of abuseDopaminergic neuronsMesolimbic systemDopamine releaseDopamine systemMutant miceMiceNicotineNeurotransmitter dopamineStriatumReceptorsNeuronsReleaseBrain