2024
Effects of ketamine on GABAergic and glutamatergic activity in the mPFC: biphasic recruitment of GABA function in antidepressant-like responses
Fogaça M, Daher F, Picciotto M. Effects of ketamine on GABAergic and glutamatergic activity in the mPFC: biphasic recruitment of GABA function in antidepressant-like responses. Neuropsychopharmacology 2024, 1-12. PMID: 39390105, DOI: 10.1038/s41386-024-02002-1.Peer-Reviewed Original ResearchNovelty suppressed feeding testMedial prefrontal cortexSucrose splash testEffects of ketamineAntidepressant-like responseMajor depressive disorderGABAergic activityGABA interneuronsGlutamatergic activityGABA neuronsSustained antidepressant effectsGABA neuron activityLow dose of ketamineAdministration of ketamineDose of ketamineAntidepressant responseAntidepressant developmentSplash testAntidepressant effectsPrefrontal cortexDepressive disorderChemogenetic inhibitionBehavioral actionsAssociated with disruptionGABA functionMedial 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 encodingAlternative translation initiation produces synaptic organizer proteoforms with distinct localization and functions
Lee P, Sun Y, Soares A, Fai C, Picciotto M, Guo J. Alternative translation initiation produces synaptic organizer proteoforms with distinct localization and functions. Molecular Cell 2024, 84: 3967-3978.e8. PMID: 39317199, PMCID: PMC11490368, DOI: 10.1016/j.molcel.2024.08.032.Peer-Reviewed Original ResearchTranslation initiation siteNeuronal pentraxin receptorAUG translational initiation siteAlternative translation initiation sitesN-terminal signal sequenceN-terminal transmembrane domainRNA secondary structureAlternative translation initiationN-terminal extensionTranslation initiationSignal sequenceProtein isoformsProtein localizationAUG initiatorTransmembrane domainWidespread mechanismSecondary structureInitiation siteAlternative usageAMPA-type glutamate receptorsProteoformsSecreted factorsProteinReduced AMPA receptorMRNAFunctionally refined encoding of threat memory by distinct populations of basal forebrain cholinergic projection neurons
Rajebhosale P, Ananth M, Kim R, Crouse R, Jiang L, López-Hernández G, Zhong C, Arty C, Wang S, Jone A, Desai N, Li Y, Picciotto M, Role L, Talmage D. Functionally refined encoding of threat memory by distinct populations of basal forebrain cholinergic projection neurons. ELife 2024, 13: e86581. PMID: 38363713, PMCID: PMC10928508, DOI: 10.7554/elife.86581.Peer-Reviewed Original ResearchBasolateral amygdalaCholinergic neuronsThreatening stimuliMemory recallPredator odorDefensive behaviorResponse to predator odorBasal forebrain cholinergic projection neuronsBasal forebrain of micePosterior substantia innominataForebrain of miceSource of cholinergic inputCholinergic basal forebrainIncreased intrinsic excitabilityCholinergic projection neuronsThreat memoryFoot shockAversive stimuliChemogenetic silencingCholinergic inputSubstantia innominataPopulation of cholinergic neuronsNucleus basalisIntrinsic excitabilityProjection neuronsThe 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
Nicotine addiction: More than just dopamine
Kim K, Picciotto M. Nicotine addiction: More than just dopamine. Current Opinion In Neurobiology 2023, 83: 102797. PMID: 37832393, PMCID: PMC10842238, DOI: 10.1016/j.conb.2023.102797.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsNicotine addictionImportant public health problemAnti-tobacco messagingNicotine-induced behaviorsPublic health problemReward-related behaviorsNovel glutamateDopaminergic mechanismsSmoking cessationNicotine reinforcementMesolimbic systemNicotine seekingRecent studiesTherapeutic targetNicotine aversionHealth problemsActive investigationAdditional pathwaysSex differencesNicotine vapingMolecular mechanismsWithdrawalAddictionPathwayMolecular basisNicotinic regulation of microglia: potential contributions to addiction
Soares A, Picciotto M. Nicotinic regulation of microglia: potential contributions to addiction. Journal Of Neural Transmission 2023, 131: 425-435. PMID: 37778006, PMCID: PMC11189589, DOI: 10.1007/s00702-023-02703-9.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsNeuroimmune signalingNicotine addictionΑ7 nicotinic acetylcholine receptorAnti-inflammatory cascadeAnti-inflammatory effectsEffects of nicotineAnti-inflammatory compoundsIntracellular calcium concentrationNicotinic acetylcholine receptorsMicroglial polarizationNicotinic regulationMicroglial activityMicroglial signalingImmunomodulatory effectsImmunosuppressive effectsWithdrawal symptomsCytokine releaseCircuit disruptionPreclinical literaturePreclinical studiesΑ7 nAChRsCircuit dysregulationNicotine dependenceMicrogliaAcetylcholine receptorsHow 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 ResearchM1 acetylcholine receptors in somatostatin interneurons contribute to GABAergic and glutamatergic plasticity in the mPFC and antidepressant-like responses
Fogaça M, Wu M, Li C, Li X, Duman R, Picciotto M. M1 acetylcholine receptors in somatostatin interneurons contribute to GABAergic and glutamatergic plasticity in the mPFC and antidepressant-like responses. Neuropsychopharmacology 2023, 48: 1277-1287. PMID: 37142667, PMCID: PMC10354201, DOI: 10.1038/s41386-023-01583-7.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsMedial prefrontal cortexGABAergic functionSomatostatin interneuronsSST interneuronsGlutamatergic plasticityAcetylcholine receptorsNon-selective muscarinic receptor antagonistRapid antidepressant-like effectsAntidepressant-like responseImpaired synaptic plasticityChronic unpredictable stressMuscarinic receptor antagonistModulation of excitatoryMajor depressive disorderScopolamine-induced increaseStress-induced impairmentM1 acetylcholine receptorExpression of GABAergicAntidepressant developmentGlutamatergic markersReceptor antagonistDepressive disorderLimbic regionsUnpredictable stressPathophysiology 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
Muscarinic antagonists impair multiple aspects of operant discrimination learning and performance
Yousuf H, Girardi E, Crouse R, Picciotto M. Muscarinic antagonists impair multiple aspects of operant discrimination learning and performance. Neuroscience Letters 2022, 794: 137025. PMID: 36529388, PMCID: PMC9812939, DOI: 10.1016/j.neulet.2022.137025.Peer-Reviewed Original ResearchConceptsOperant discriminationOperant discrimination learningCue-reward associationsLong-term memoryMultiple training sessionsPost-session injectionsCue associationsReward-related respondingMemory processesDiscrimination learningMaladaptive formsImpaired consolidationFood rewardSuccessful learningNose pokesDifferent learningPre-session injectionsTraining sessionsRewardTaskMemoryLearningMultiple aspectsEnvironmental cuesMuscarinic acetylcholine receptor familyLooking Back on My Time as Editor-in-Chief
Picciotto M. Looking Back on My Time as Editor-in-Chief. Journal Of Neuroscience 2022, 42: 9294-9295. PMID: 36517253, PMCID: PMC9794375, DOI: 10.1523/jneurosci.2137-22.2022.Peer-Reviewed Original ResearchActivity 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 ResearchNicotine Pharmacology, Abuse, and Addiction
Miller M, Picciotto M. Nicotine Pharmacology, Abuse, and Addiction. 2022, 4083-4101. DOI: 10.1007/978-3-030-88832-9_157.ChaptersTobacco useDrugs of abuseNeuropsychiatric disordersGreat public health relevanceGreat public health concernMesolimbic dopamine systemPre-clinical studiesPublic health concernPublic health relevanceNicotinic acetylcholine receptorsIonotropic neurotransmitter receptorsPrimary psychoactive componentSubstantial health risksNicotine exposureNicotine actsSustained tobacco useNicotine pharmacologyRewarding effectsNicotine addictionDopamine systemNervous systemNeurotransmitter receptorsNicotine useAcetylcholine receptorsAddictive propertiesACh 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 IIPositive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear
Lee B, Pothula S, Wu M, Kang H, Girgenti MJ, Picciotto MR, DiLeone RJ, Taylor JR, Duman RS. Positive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear. Molecular Psychiatry 2022, 27: 2580-2589. PMID: 35418600, PMCID: PMC9135632, DOI: 10.1038/s41380-022-01498-7.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderFear extinctionInfralimbic medial prefrontal cortexFear conditioning modelEnhanced fear extinctionFear-based behaviorsProlonged stress modelMedial prefrontal cortexSpontaneous recoveryIL-mPFCPTSD modelPTSD treatmentStress disorderPrefrontal cortexSPS modelN-methyl-D-aspartate receptor modulatorsBrain-derived neurotrophic factorN-methyl-D-aspartate receptorsBehavioral effectsIncreased attentionMPFCPreclinical findingsPyramidal neuronsNeurotrophic factorMale miceSex 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 studiesDrinkingDifferencesAmygdalaPathwayStudyWomenA Change in Scope and a Call for Papers
Picciotto M. A Change in Scope and a Call for Papers. Journal Of Neuroscience 2022, 42: 531-531. PMID: 35082162, PMCID: PMC8805624, DOI: 10.1523/jneurosci.0038-22.2022.Commentaries, Editorials and LettersHippocampal 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