2025
An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes
Furlanis E, Dai M, Leyva Garcia B, Tran T, Vergara J, Pereira A, Gorissen B, Wills S, Vlachos A, Hairston A, Dwivedi D, Du S, McMahon J, Huang S, Morabito A, Vazquez A, Kim S, Lee A, Chang E, Razzaq T, Qazi A, Vargish G, Yuan X, Caccavano A, Hunt S, Chittajallu R, McLean N, Hewitt L, Paranzino E, Rice H, Cummins A, Plotnikova A, Mohanty A, Tangen A, Shin J, Azadi R, Eldridge M, Alvarez V, Averbeck B, Alyahyay M, Vallejo T, Soheib M, Vattino L, MacGregor C, Chatain C, Banks E, Olah V, Naskar S, Hill S, Liebergall S, Badiani R, Hyde L, Hanley E, Xu Q, Allaway K, Goldberg E, Rowan M, Nowakowski T, Lee S, Favuzzi E, Kaeser P, Sjulson L, Batista-Brito R, Takesian A, Ibrahim L, Iqbal A, Pelkey K, McBain C, Dimidschstein J, Fishell G, Wang Y. An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes. Neuron 2025, 113: 1525-1547.e15. PMID: 40403705, DOI: 10.1016/j.neuron.2025.05.002.Peer-Reviewed Original Research
2024
Elevated antibody binding to striatal cholinergic interneurons in patients with pediatric acute-onset neuropsychiatric syndrome
Xu J, Frankovich J, Liu R, Thienemann M, Silverman M, Farhadian B, Willett T, Manko C, Columbo L, Leibold C, Vaccarino F, Che A, Pittenger C. Elevated antibody binding to striatal cholinergic interneurons in patients with pediatric acute-onset neuropsychiatric syndrome. Brain Behavior And Immunity 2024, 122: 241-255. PMID: 39084540, PMCID: PMC11569416, DOI: 10.1016/j.bbi.2024.07.044.Peer-Reviewed Original ResearchPediatric Autoimmune Neuropsychiatric Disorders Associated with StreptococcusPediatric acute-onset neuropsychiatric syndromeStriatal cholinergic interneuronsCholinergic interneuronsObsessive-compulsive symptomsModulate basal ganglia functionNeuropsychiatric syndromeSignificant obsessive-compulsive symptomsBasal ganglia functionEx vivo brain slicesSevere food restrictionElevated antibodiesClinical historyPatient plasmaNeuropsychiatric manifestationsStreptococcus infectionBrain slicesSymptom flaresControl plasmaFood restrictionSerum antibodiesHuman brainInfectionAbrupt onsetClinical contextSex differences in the distribution and density of regulatory interneurons in the striatum
Van Zandt M, Flanagan D, Pittenger C. Sex differences in the distribution and density of regulatory interneurons in the striatum. Frontiers In Cellular Neuroscience 2024, 18: 1415015. PMID: 39045533, PMCID: PMC11264243, DOI: 10.3389/fncel.2024.1415015.Peer-Reviewed Original ResearchFast spiking interneuronsCholinergic interneuronsDorsal striatumSex differencesTourette syndromeVentral striatumNeuropsychiatric disordersSomatostatin expressionContext of psychopathologyHuman neuropsychiatric disordersBasal ganglia functionInvestigate sex differencesNucleus accumbensCaudate-putamenBehavioral pathologyStriatumSomatostatin-expressing interneuronsStriatal interneuronsGABAergic interneuronsMale miceStereological quantificationFemale miceInterneuronsDisordersAccumbensActivation of M4 muscarinic receptors in the striatum reduces tic‐like behaviours in two distinct murine models of Tourette syndrome
Cadeddu R, Braccagni G, Branca C, van Luik E, Pittenger C, Thomsen M, Bortolato M. Activation of M4 muscarinic receptors in the striatum reduces tic‐like behaviours in two distinct murine models of Tourette syndrome. British Journal Of Pharmacology 2024, 181: 3064-3081. PMID: 38689378, DOI: 10.1111/bph.16392.Peer-Reviewed Original ResearchPositive allosteric modulatorsD1CT-7 miceTourette syndromeMouse model of TSStriatal cholinergic interneuronsTic-like behavioursC-Fos levelsModel of TSActivate c-fosM4 muscarinic receptorsMuscarinic receptorsStriatal acetylcholineMouse modelStriatal expressionTic-likeStriatal levelsCholinergic interneuronsVU0467154Current pharmacotherapyXanomelineReceptor agonistsAllosteric modulatorsC-fosReceptor antagonistStriatum
2023
Prefrontal allopregnanolone mediates the adverse effects of acute stress in a mouse model of tic pathophysiology
Cadeddu R, Van Zandt M, Santovito L, Odeh K, Anderson C, Flanagan D, Nordkild P, Pinna G, Pittenger C, Bortolato M. Prefrontal allopregnanolone mediates the adverse effects of acute stress in a mouse model of tic pathophysiology. Neuropsychopharmacology 2023, 48: 1288-1299. PMID: 37198434, PMCID: PMC10354086, DOI: 10.1038/s41386-023-01603-6.Peer-Reviewed Original ResearchConceptsEffects of allopregnanoloneTourette syndromeCholinergic interneuronsAcute stressPrefrontal cortexPrepulse inhibitionTic pathophysiologyMouse modelAdverse effectsStriatal cholinergic interneuronsDeficient prepulse inhibitionSeverity of ticsPost-mortem studiesPharmacological antagonismPPI deficitsNeurosteroid allopregnanoloneMale miceAdministration doseAllopregnanoloneAnimal modelsBehavioral pathologySymptom severityAcute stressorYoung adulthoodAP levels
2022
Cellular and Molecular Pathology in Tourette Syndrome
Fasching L, Brady M, Vaccarino F. Cellular and Molecular Pathology in Tourette Syndrome. 2022, 171-183. DOI: 10.1093/med/9780197543214.003.0012.ChaptersTourette syndromeBasal gangliaAminobutyric acid-ergic interneuronsActive cholinergic interneuronsPathophysiology of TSCholinergic interneuronsPathological findingsMicroglial cellsTic disordersCaudate nucleusCortical hemispherePathogenic mechanismsInterneuronsSyndromeMolecular pathologyGangliaProminent increaseAvailable literatureInflammationPathophysiologyPutamenFindingsPathology
2020
Propranolol Relieves L-Dopa-Induced Dyskinesia in Parkinsonian Mice
Shi Z, Bamford IJ, McKinley JW, Devi SPS, Vahedipour A, Bamford NS. Propranolol Relieves L-Dopa-Induced Dyskinesia in Parkinsonian Mice. Brain Sciences 2020, 10: 903. PMID: 33255421, PMCID: PMC7760026, DOI: 10.3390/brainsci10120903.Peer-Reviewed Original ResearchL-DOPA-induced dyskinesiaL-DOPAStriatal acetylcholineDA deficiencyMovement disordersDA availabilityHypokinetic movement disordersStriatal cholinergic interneuronsHyperkinetic movement disordersDopa decarboxylase inhibitorElectrophysiological experimentsOpen field testingStriatal ChIsParkinsonian miceCholinergic interneuronsMotor dysfunctionTherapeutic optionsMotor hyperactivityParadoxical riseDA ratioMotor functionDecarboxylase inhibitorDopamine insufficiencyΒ-ARsΒ-ARAntibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity
Xu J, Liu RJ, Fahey S, Frick L, Leckman J, Vaccarino F, Duman RS, Williams K, Swedo S, Pittenger C. Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity. American Journal Of Psychiatry 2020, 178: 48-64. PMID: 32539528, PMCID: PMC8573771, DOI: 10.1176/appi.ajp.2020.19070698.Peer-Reviewed Original ResearchConceptsStriatal cholinergic interneuronsCholinergic interneuronsMouse brain slicesObsessive-compulsive disorderControl subjectsBrain slicesPediatric autoimmune neuropsychiatric disordersIntravenous immunoglobulin treatmentAutoimmune neuropsychiatric disordersAcute mouse brain slicesParvalbumin-expressing GABAergic interneuronsPediatric obsessive-compulsive disorderBrain antigensImmunoglobulin treatmentBaseline serumStreptococcal infectionCritical cellular targetsSymptom improvementGABAergic interneuronsInduced autoimmunityIgG antibodiesMouse slicesIndependent cohortBehavioral pathologyNeuron types
2017
Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum
Frick L, Rapanelli M, Jindachomthong K, Grant P, Leckman JF, Swedo S, Williams K, Pittenger C. Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum. Brain Behavior And Immunity 2017, 69: 304-311. PMID: 29233751, PMCID: PMC5857467, DOI: 10.1016/j.bbi.2017.12.004.Peer-Reviewed Original ResearchConceptsGroup A beta-hemolytic streptococciCholinergic interneuronsPediatric Autoimmune Neuropsychiatric Disorder AssociatedNeuropsychiatric Disorder AssociatedStriatal cholinergic interneuronsStriatum of miceBeta-hemolytic streptococciBrain antigensPANDAS patientsIntravenous immunoglobulinStriatal interneuronsNeuropsychiatric symptomsObsessive-compulsive disorderSymptom improvementGABAergic interneuronsClinical trialsHealthy controlsDisorders AssociatedTic disordersChildhood onsetInterneuronsLocus of pathologyElevated bindingAntibodiesStriatumTargeted Interneuron Depletion in the Dorsal Striatum Produces Autism-like Behavioral Abnormalities in Male but Not Female Mice
Rapanelli M, Frick LR, Xu M, Groman SM, Jindachomthong K, Tamamaki N, Tanahira C, Taylor JR, Pittenger C. Targeted Interneuron Depletion in the Dorsal Striatum Produces Autism-like Behavioral Abnormalities in Male but Not Female Mice. Biological Psychiatry 2017, 82: 194-203. PMID: 28347488, PMCID: PMC5374721, DOI: 10.1016/j.biopsych.2017.01.020.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnxietyAutistic DisorderConditioning, OperantCorpus StriatumDisease Models, AnimalExploratory BehaviorFemaleImmunohistochemistryInterneuronsMaleMice, TransgenicMotor ActivityPrepulse InhibitionRibosomal Protein S6 Kinases, 90-kDaSex CharacteristicsSocial BehaviorStereotyped BehaviorSynaptic TransmissionConceptsCholinergic interneuronsTourette syndromeDorsal striatumFemale miceMale miceLarge cholinergic interneuronsAutism spectrum disorderToxin-mediated ablationAutism-like behavioral abnormalitiesAnxiety-like behaviorActivity-dependent signalingMale predominanceNeuronal abnormalitiesPotential relevancePreclinical modelsNormal miceInterneuron typesInterneuronal populationsBehavioral abnormalitiesBehavioral pathologyStriatumDimorphic mannerNeuropsychiatric disordersInterneuronsBehavioral effects
2016
Nicotine Modifies Corticostriatal Plasticity and Amphetamine Rewarding Behaviors in Mice1,2,3
Storey GP, Gonzalez-Fernandez G, Bamford IJ, Hur M, McKinley JW, Heimbigner L, Minasyan A, Walwyn WM, Bamford NS. Nicotine Modifies Corticostriatal Plasticity and Amphetamine Rewarding Behaviors in Mice1,2,3. ENeuro 2016, 3: eneuro.0095-15.2015. PMID: 26866057, PMCID: PMC4745180, DOI: 10.1523/eneuro.0095-15.2015.Peer-Reviewed Original ResearchMeSH KeywordsAction Potentialsalpha7 Nicotinic Acetylcholine ReceptorAmphetamineAnimalsCentral Nervous System StimulantsCholinergic NeuronsConditioning, OperantCorpus StriatumDrug-Seeking BehaviorFemaleMaleMiceMice, Inbred C57BLMotor ActivityMotor CortexNeural PathwaysNeuronal PlasticityNicotineNicotinic AgonistsReceptors, NicotinicRewardSelf AdministrationConceptsCorticostriatal activityAmphetamine challengeGlutamate releaseLocomotor sensitizationDirect pathway medium spiny neuronsAmphetamine-induced locomotor sensitizationActive cholinergic interneuronsAmphetamine-seeking behaviorSubsequent drug challengeMedium spiny neuronsActivity ex vivoNicotinic acetylcholine receptorsDrug-seeking behaviorPeriod of abstinenceSelf-administer amphetamineDrugs of abuseSelf-administering miceDrug-taking behaviorDwelling catheterAmphetamine withdrawalCholinergic interneuronsGlutamatergic activityPresynaptic depressionPotentiating responseSpiny neurons
2015
Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome
Xu M, Kobets A, Du JC, Lennington J, Li L, Banasr M, Duman RS, Vaccarino FM, DiLeone RJ, Pittenger C. Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 893-898. PMID: 25561540, PMCID: PMC4311862, DOI: 10.1073/pnas.1419533112.Peer-Reviewed Original ResearchConceptsTourette syndromeCholinergic interneuronsDorsolateral striatumSensorimotor gatingD-amphetamine challengeLarge cholinergic interneuronsSpecific cell ablationInterneuron deficitsStriatal interneuronsAcute administrationGABAergic markersDopaminergic drugsAvailable treatmentsPostmortem studiesPrepulse inhibitionTic disordersSevere diseaseHuman putamenMotor coordinationInterneuronsTargeted ablationSevere endStriatumAcute stressGilles de
2013
Cellular and Molecular Pathology in Tourette Syndrome
Vaccarino F, Kataoka-Sasaki Y, Lennington J. Cellular and Molecular Pathology in Tourette Syndrome. 2013, 205-220. DOI: 10.1093/med/9780199796267.003.0010.Chapters
2009
Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome
Kataoka Y, Kalanithi PS, Grantz H, Schwartz ML, Saper C, Leckman JF, Vaccarino FM. Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome. The Journal Of Comparative Neurology 2009, 518: 277-291. PMID: 19941350, PMCID: PMC2846837, DOI: 10.1002/cne.22206.Peer-Reviewed Original ResearchConceptsMedium spiny neuronsCholinergic interneuronsTourette syndromeNormal controlsCholinergic striatal interneuronsNumber of parvalbuminBrains of patientsCaudate nucleus volumeUnbiased stereological analysisStriatal interneuronsOngoing motor behaviorCholinergic cellsTotal neuronsCholine acetyltransferaseSpiny neuronsLimbic regionsStriatum of individualsTS patientsPostmortem brainsThalamic controlSensorimotor regionsInterneuronsCellular abnormalitiesNeuron firingTS subjectsDecreased Number of Parvalbumin and Cholinergic Interneurons in the Striatum of Individuals with Tourette Syndrome
Kataoka-Sasaki Y, Kalanithi P, Grantz H, Schwartz M, Saper C, Leckman J, Vaccarino F. Decreased Number of Parvalbumin and Cholinergic Interneurons in the Striatum of Individuals with Tourette Syndrome. Neuroscience Research 2009, 65: s258. DOI: 10.1016/j.neures.2009.09.1470.Peer-Reviewed Original Research
2008
Developmentally regulated and evolutionarily conserved expression of SLITRK1 in brain circuits implicated in Tourette syndrome
Stillman AA, Krsnik Ž, Sun J, Rašin M, State MW, šestan N, Louvi A. Developmentally regulated and evolutionarily conserved expression of SLITRK1 in brain circuits implicated in Tourette syndrome. The Journal Of Comparative Neurology 2008, 513: 21-37. PMID: 19105198, PMCID: PMC3292218, DOI: 10.1002/cne.21919.Peer-Reviewed Original ResearchConceptsCorticostriatal-thalamocortical circuitsSingle-pass transmembrane proteinTourette syndromeEtiology of TSRare sequence variantsTransmembrane proteinSLITRK1Expression patternsCortical pyramidal neuronsCytoplasmic vesiclesDevelopmental expressionMember 1 geneSequence variantsAxonal repulsionSlit familyDendritic patterningDirect output pathwayCholinergic interneuronsPyramidal neuronsProjection neuronsStriatal expressionMotor ticsSomatodendritic compartmentDevelopmental neuropsychiatric disordersPatch compartment
2006
362 ROLE OF ACETYLCHOLINE IN PSYCHOSTIMULANT ADDICTION.
Kumar T, Joyce J, Bamford N. 362 ROLE OF ACETYLCHOLINE IN PSYCHOSTIMULANT ADDICTION. Journal Of Investigative Medicine 2006, 54: s142. DOI: 10.2310/6650.2005.x0004.361.Peer-Reviewed Original ResearchMedium spiny neuronsWithdrawal day 1Nucleus accumbensCholinergic activationCholinergic interneuronsBasal gangliaSpiny neuronsDorsolateral striatumDay 1Striatal medium spiny neuronsAdult C57B1/6 miceCaudal nucleus accumbensChronic METH treatmentExcitatory glutamatergic projectionsWithdrawal day 10Striatal cholinergic interneuronsC-fosTreatment of miceC-Fos immunoreactivityRole of acetylcholineNumber of ChATImmediate early gene expressionChronic METHCortical terminalsGlutamate release
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