2024
The endogenous opioid system in the medial prefrontal cortex mediates ketamine’s antidepressant-like actions
Jiang C, DiLeone R, Pittenger C, Duman R. The endogenous opioid system in the medial prefrontal cortex mediates ketamine’s antidepressant-like actions. Translational Psychiatry 2024, 14: 90. PMID: 38346984, PMCID: PMC10861497, DOI: 10.1038/s41398-024-02796-0.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexAction of ketamineEndogenous opioid systemAntidepressant-like actionOpioid systemB-endorphinKetamine treatmentAntidepressant-like actions of ketamineBehavioral actions of ketamineAntidepressant actions of ketamineBehavioral effects of ketamineSingle dose of ketamineAntidepressant-like effectsLevels of B-endorphinAcute systemic administrationEffects of ketamineDose of ketamineOpioid receptor antagonistAntidepressant actionPrefrontal cortexActivation of opioid receptorsBehavioral effectsBehavioral actionsCompetitive opioid receptor antagonistOpioid receptors
2023
Postinfectious Inflammation, Autoimmunity, and Obsessive-Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection, and Pediatric Acute-Onset Neuropsychiatric Disorder
Vreeland A, Calaprice D, Or-Geva N, Frye R, Agalliu D, Lachman H, Pittenger C, Pallanti S, Williams K, Ma M, Thienemann M, Gagliano A, Mellins E, Frankovich J. Postinfectious Inflammation, Autoimmunity, and Obsessive-Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection, and Pediatric Acute-Onset Neuropsychiatric Disorder. Developmental Neuroscience 2023, 45: 361-374. PMID: 37742615, DOI: 10.1159/000534261.Peer-Reviewed Original ResearchConceptsPediatric acute-onset neuropsychiatric syndromeObsessive-compulsive disorderGroup A streptococciSydenham's choreaNeuropsychiatric disordersStreptococcal infectionAcute-onset obsessive-compulsive disorderPediatric autoimmune neuropsychiatric disorders associated with streptococcal infectionsAssociated with streptococcal infectionsAnimal modelsPediatric autoimmune neuropsychiatric disordersAnti-neuronal autoantibodiesAutoimmune neuropsychiatric disordersTriggered by infectionModulate neuronal activityRandomized clinical trialsNeuropsychiatric syndromeNeuropsychiatric manifestationsRheumatologic diseasesClinical trialsA streptococciNeural antigensBasal gangliaClinical syndromeNeuronal activityPrefrontal 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 levels5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice
Jefferson S, Gregg I, Dibbs M, Liao C, Wu H, Davoudian P, Woodburn S, Wehrle P, Sprouse J, Sherwood A, Kaye A, Pittenger C, Kwan A. 5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice. Neuropsychopharmacology 2023, 48: 1257-1266. PMID: 37015972, PMCID: PMC10354037, DOI: 10.1038/s41386-023-01572-w.Peer-Reviewed Original ResearchConceptsMouse medial frontal cortexEarly phase clinical studiesDendritic spine densityHead-twitch responseDose-dependent increaseStructural neural plasticityMedial frontal cortexSpine densityClinical studiesFrontal cortexLong-term effectsDendritic spinesMental illnessNeural plasticitySpine formationPatient accessSubjective effectsNeural consequencesPotential therapeuticsSerotonergic psychedelicsAnxiety symptomsNeural mechanismsUltrasonic vocalizationsElevated ratesMiceThe histamine H3 receptor modulates dopamine D2 receptor–dependent signaling pathways and mouse behaviors
Xu J, Pittenger C. The histamine H3 receptor modulates dopamine D2 receptor–dependent signaling pathways and mouse behaviors. Journal Of Biological Chemistry 2023, 299: 104583. PMID: 36871761, PMCID: PMC10139999, DOI: 10.1016/j.jbc.2023.104583.Peer-Reviewed Original ResearchConceptsStress-activated protein kinase 1Receptor-dependent signaling pathwaysSerine/threonineGlycogen synthase kinase 3 betaSynthase kinase 3 betaProtein kinase 1Phosphorylation of mitogenBiochemical approachesMolecular mechanismsKinase 1Signaling pathwaysProximity ligationBeta signalingBiochemical levelPhosphorylation levelsReceptorsActivationHistamine H3 receptorsPhosphorylationSignalingThreonineAktSpiny projection neuronsD2R functionBetter understandingCholinergic neurons in the basal forebrain are involved in behavioral abnormalities associated with Cul3 deficiency: Role of prefrontal cortex projections in cognitive deficits
Rapanelli M, Wang W, Hurley E, Feltri M, Pittenger C, Frick L, Yan Z. Cholinergic neurons in the basal forebrain are involved in behavioral abnormalities associated with Cul3 deficiency: Role of prefrontal cortex projections in cognitive deficits. Translational Psychiatry 2023, 13: 22. PMID: 36693858, PMCID: PMC9873627, DOI: 10.1038/s41398-023-02306-8.Peer-Reviewed Original ResearchConceptsBF cholinergic neuronsCholinergic neuronsBasal forebrainCognitive deficitsPrefrontal cortexBehavioral abnormalitiesASD-like behavioral abnormalitiesAutism spectrum disorderPrefrontal cortex projectionsSignificant cognitive impairmentChemogenetic stimulationCholinergic dysfunctionCholinergic projectionsChemogenetic inhibitionRisk factorsHealthy miceCortex projectionsPathogenic mechanismsSensory gatingCognitive impairmentNeuronsAbnormalitiesMiceDiminished activityFunction mutations
2020
Antibodies 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
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
2014
Histidine Decarboxylase Deficiency Causes Tourette Syndrome: Parallel Findings in Humans and Mice
Baldan LC, Williams KA, Gallezot JD, Pogorelov V, Rapanelli M, Crowley M, Anderson GM, Loring E, Gorczyca R, Billingslea E, Wasylink S, Panza KE, Ercan-Sencicek AG, Krusong K, Leventhal BL, Ohtsu H, Bloch MH, Hughes ZA, Krystal JH, Mayes L, de Araujo I, Ding YS, State MW, Pittenger C. Histidine Decarboxylase Deficiency Causes Tourette Syndrome: Parallel Findings in Humans and Mice. Neuron 2014, 81: 77-90. PMID: 24411733, PMCID: PMC3894588, DOI: 10.1016/j.neuron.2013.10.052.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAmphetamineAnimalsBrainChildDopamine AgonistsDopamine AntagonistsExploratory BehaviorFemaleHistidine DecarboxylaseHumansMaleMaze LearningMiceMice, KnockoutMiddle AgedMutationOxazinesRacloprideRadionuclide ImagingStereotyped BehaviorTime FactorsTourette SyndromeTryptophanYoung AdultConceptsTourette syndromeHA infusionKnockout miceD2/D3 receptor bindingDecarboxylase deficiencyDopamine D2 antagonist haloperidolCortico-basal ganglia circuitsStriatal DA levelsHDC knockout miceD3 receptor bindingImmediate early gene FosD2 antagonist haloperidolRare genetic causeBiosynthesis of histamineStriatal DARare causeBasal gangliaDA levelsAntagonist haloperidolGanglia circuitsPrepulse inhibitionMiceReceptor bindingGenetic causeHistidine decarboxylase
2001
Some Forms of cAMP-Mediated Long-Lasting Potentiation Are Associated with Release of BDNF and Nuclear Translocation of Phospho-MAP Kinase
Patterson S, Pittenger C, Morozov A, Martin K, Scanlin H, Drake C, Kandel E. Some Forms of cAMP-Mediated Long-Lasting Potentiation Are Associated with Release of BDNF and Nuclear Translocation of Phospho-MAP Kinase. Neuron 2001, 32: 123-140. PMID: 11604144, DOI: 10.1016/s0896-6273(01)00443-3.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsBrain-Derived Neurotrophic FactorCell NucleusColforsinCyclic AMPDendritesExcitatory Postsynaptic PotentialsLigandsLong-Term PotentiationMembrane PotentialsMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMicroscopy, ImmunoelectronMitogen-Activated Protein KinasesNeuronal PlasticityPhosphorylationPresynaptic TerminalsReceptor, trkBTheta Rhythm
1999
The past, the future and the biology of memory storage
Kandel E, Pittenger C. The past, the future and the biology of memory storage. Philosophical Transactions Of The Royal Society B Biological Sciences 1999, 354: 2027-2052. PMID: 10670023, PMCID: PMC1692699, DOI: 10.1098/rstb.1999.0542.Peer-Reviewed Original Research