2024
Medial prefrontal cortex acetylcholine signaling mediates the ability to learn an active avoidance response following learned helplessness training
Abdulla Z, Mineur Y, Crouse R, Etherington I, Yousuf H, Na J, Picciotto M. Medial prefrontal cortex acetylcholine signaling mediates the ability to learn an active avoidance response following learned helplessness training. Neuropsychopharmacology 2024, 1-9. PMID: 39362985, DOI: 10.1038/s41386-024-02003-0.Peer-Reviewed Original ResearchMedial prefrontal cortexACh levelsInescapable stressorEscape performanceExposure to inescapable stressorsAcetylcholine signalingLearned helplessness taskLearned helplessness trainingStress-related circuitsActive avoidance taskActive avoidance testActive avoidance responseElevation of acetylcholineIncreased ACh levelsStress-related behaviorsImpaired escape performanceIncreased brain levelsTop-down controlHelplessness trainingPrefrontal cortexAvoidance taskChemogenetic inhibitionMaladaptive behaviorsAvoidance testNegative encodingThe role of neurosteroids in posttraumatic stress disorder and alcohol use disorder: A review of 10 years of clinical literature and treatment implications
Peltier M, Verplaetse T, Altemus M, Zakiniaeiz Y, Ralevski E, Mineur Y, Gueorguieva R, Picciotto M, Cosgrove K, Petrakis I, McKee S. The role of neurosteroids in posttraumatic stress disorder and alcohol use disorder: A review of 10 years of clinical literature and treatment implications. Frontiers In Neuroendocrinology 2024, 73: 101119. PMID: 38184208, PMCID: PMC11185997, DOI: 10.1016/j.yfrne.2023.101119.Peer-Reviewed Original ResearchPosttraumatic stress disorderAlcohol use disorderStress disorderContext of PTSDPTSD/AUDConcurrent posttraumatic stress disorderUnderlying neurobiological mechanismsUse disordersAlcohol-related variablesNeurobiological mechanismsPTSD diagnosisTreatment developmentTreatment implicationsBody of literatureNovel interventionsClinical literatureRole of neurosteroidsDisordersTreatment outcomesYears of researchAlcohol consumptionExogenous pregnenolonePharmacological treatmentBiological variablesAllopregnanolone
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 ResearchDeveloping Researchers with Expertise in Sex as a Biological Variable through SCORE Career Enhancement Core Center Programs
Zakiniaeiz Y, Peltier M, Mineur Y, Gueorguieva R, Picciotto M, Petrakis I, Cosgrove K, McKee S. Developing Researchers with Expertise in Sex as a Biological Variable through SCORE Career Enhancement Core Center Programs. Journal Of Women's Health 2023, 32: 852-857. PMID: 37585509, PMCID: PMC10457604, DOI: 10.1089/jwh.2023.0015.Peer-Reviewed Original ResearchPathophysiology of nAChRs: Limbic circuits and related disorders
Mineur Y, Soares A, Etherington I, Abdulla Z, Picciotto M. Pathophysiology of nAChRs: Limbic circuits and related disorders. Pharmacological Research 2023, 191: 106745. PMID: 37011774, DOI: 10.1016/j.phrs.2023.106745.Peer-Reviewed Original ResearchConceptsDepressive disorderMedication developmentLimbic system areasPreclinical pharmacological studiesHuman epidemiological studiesHuman affective disordersNicotinic acetylcholine receptorsAntidepressant efficacyClinical evidenceLimbic circuitsNicotine intakePreclinical modelsSpecific nAChRsEpidemiological studiesCurrent therapeuticsAffective disordersAcetylcholine receptorsRelated disordersPharmacological studiesStress disorderDisordersEtiology of anxietyNAChRsRelevant targetsEfficacy
2022
Activity of a direct VTA to ventral pallidum GABA pathway encodes unconditioned reward value and sustains motivation for reward
Zhou WL, Kim K, Ali F, Pittenger ST, Calarco CA, Mineur YS, Ramakrishnan C, Deisseroth K, Kwan AC, Picciotto MR. Activity of a direct VTA to ventral pallidum GABA pathway encodes unconditioned reward value and sustains motivation for reward. Science Advances 2022, 8: eabm5217. PMID: 36260661, PMCID: PMC9581470, DOI: 10.1126/sciadv.abm5217.Peer-Reviewed Original ResearchACh 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 IISex differences in stress-induced alcohol intake: a review of preclinical studies focused on amygdala and inflammatory pathways
Mineur YS, Garcia-Rivas V, Thomas MA, Soares AR, McKee SA, Picciotto MR. Sex differences in stress-induced alcohol intake: a review of preclinical studies focused on amygdala and inflammatory pathways. Psychopharmacology 2022, 239: 2041-2061. PMID: 35359158, PMCID: PMC9704113, DOI: 10.1007/s00213-022-06120-w.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAlcohol intakeInflammatory pathwaysAlcohol drinkingStress-induced alcohol drinkingSex differencesSex-dependent effectsStress-induced alcoholEffects of stressPreclinical behavioral modelsAlcohol-dependent behaviorsMicroglial activationClinical studiesPreclinical studiesInflammatory signalingNeuronal functionAlcohol seekingIntakeFuture studiesDrinkingDifferencesAmygdalaPathwayStudyWomenHippocampal 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
2021
Sex differences in progestogen- and androgen-derived neurosteroids in vulnerability to alcohol and stress-related disorders
Peltier MR, Verplaetse TL, Mineur YS, Gueorguieva R, Petrakis I, Cosgrove KP, Picciotto MR, McKee SA. Sex differences in progestogen- and androgen-derived neurosteroids in vulnerability to alcohol and stress-related disorders. Neuropharmacology 2021, 187: 108499. PMID: 33600842, PMCID: PMC7992136, DOI: 10.1016/j.neuropharm.2021.108499.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsStress-related disordersAlcohol useMajor depressive disorderAlcohol-related disordersAlcohol use disorderPosttraumatic stress disorderStress regulation systemComplex comorbiditiesDepressive disorderProblematic alcohol useUse disordersAlcohol misuseTherapeutic potentialTrauma exposureSubstance abuseStress disorderAnxiety disordersDisordersExposure resultsProgestogensNeurosteroidsNegative affectWomenComorbiditiesMale counterparts
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 acquisitionCuesOrigin 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: 1660. PMID: 32946784, DOI: 10.1016/j.cell.2020.08.044.Peer-Reviewed Original ResearchConverging 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 levelsEncodingAChCholinergic modulation of circuits involved in stress-related behaviors
Picciotto M, Mineur Y. Cholinergic modulation of circuits involved in stress-related behaviors. IBRO Neuroscience Reports 2019, 6: s28. DOI: 10.1016/j.ibror.2019.07.080.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsVariability 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 studiesSex differences in stress-related alcohol use
Peltier MR, Verplaetse TL, Mineur YS, Petrakis IL, Cosgrove KP, Picciotto MR, McKee SA. Sex differences in stress-related alcohol use. Neurobiology Of Stress 2019, 10: 100149. PMID: 30949562, PMCID: PMC6430711, DOI: 10.1016/j.ynstr.2019.100149.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAlcohol use disorderAlcohol useSex differencesAlcohol-induced neurodegenerationStress reactivityPresent narrative reviewAlcohol-related health consequencesEarly life stressBrain stress systemsOvarian hormonesPsychiatric comorbidityStress-related drinkingProblematic alcohol useUse disordersNarrative reviewBrain regionsBehavioral treatmentHealth consequencesStress systemAvailable evidenceRole of stressAlcohol addictionWomenLife stressExamination of sex