2020
Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses
Fogaça MV, Wu M, Li C, Li XY, Picciotto MR, Duman RS. Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses. Molecular Psychiatry 2020, 26: 3277-3291. PMID: 33070149, PMCID: PMC8052382, DOI: 10.1038/s41380-020-00916-y.Peer-Reviewed Original ResearchConceptsGABA interneuronsRapid antidepressant responseMajor depressive disorderAntidepressant effectsSynaptic plasticityAntidepressant responseRapid-acting antidepressantsAcetylcholine muscarinic receptor antagonistMuscarinic receptor antagonistCortical brain areasEffects of scopolamineAntidepressant actionChemogenetic inhibitionGABAergic interneuronsReceptor antagonistDepressive disorderMale miceInterneuron subtypesBrain areasInterneuronsMPFCTransient inhibitionAffective behaviorInhibitionSubtypes
2019
Perinatal nicotine exposure impairs learning of a skilled forelimb reaching task in male but not female adult mice
Lee AM, Picciotto MR. Perinatal nicotine exposure impairs learning of a skilled forelimb reaching task in male but not female adult mice. Behavioural Brain Research 2019, 367: 176-180. PMID: 30959127, PMCID: PMC6481625, DOI: 10.1016/j.bbr.2019.04.007.Peer-Reviewed Original ResearchConceptsNicotine exposureSingle-pellet reaching taskMotor tasksCortical synaptic plasticityPerinatal nicotine exposureDevelopmental nicotine exposureGross motor functionNicotine-treated animalsNicotine-induced changesFemale adult miceSkilled motor taskGross motor performanceAdverse outcomesMotor cortexFemale miceMale miceMotor functionSkilled forelimbPreclinical studiesControl animalsAdult miceImpaired learningSynaptic plasticityFemale pupsMorphologic changes
2016
CaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory
Park J, Chávez AE, Mineur YS, Morimoto-Tomita M, Lutzu S, Kim KS, Picciotto MR, Castillo PE, Tomita S. CaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory. Neuron 2016, 92: 75-83. PMID: 27667007, PMCID: PMC5059846, DOI: 10.1016/j.neuron.2016.09.002.Peer-Reviewed Original ResearchConceptsCaMKII phosphorylation siteCaMKII substratePhosphorylation sitesDependent protein kinase IIProtein kinase IIReceptor-dependent activationNMDA receptor-dependent activationProtein phosphorylationAMPAR-mediated transmissionKinase IICaMKII-dependent enhancementLong-term potentiationCaMKII phosphorylationCellular mechanismsPhosphorylationMolecular targetsAMPA receptorsCrucial mediatorSynaptic plasticityMemory formationSynaptic insertionEssential stepSynaptic transmissionActivity-dependent strengtheningBasal transmission
2012
Constitutive knockout of the membrane cytoskeleton protein beta adducin decreases mushroom spine density in the nucleus accumbens but does not prevent spine remodeling in response to cocaine
Jung Y, Mulholland PJ, Wiseman SL, Chandler LJ, Picciotto MR. Constitutive knockout of the membrane cytoskeleton protein beta adducin decreases mushroom spine density in the nucleus accumbens but does not prevent spine remodeling in response to cocaine. European Journal Of Neuroscience 2012, 37: 1-9. PMID: 23106536, PMCID: PMC3538958, DOI: 10.1111/ejn.12037.Peer-Reviewed Original ResearchConceptsNucleus accumbensCocaine administrationSpine densitySynaptic plasticityMature mushroom-shaped spinesMushroom spine densityDaily cocaine administrationMushroom-shaped spinesChronic cocaine administrationOverall spine densityElevated locomotor activityExperience-dependent remodelingLipophilic dye DiINAc slicesWT miceMushroom spinesKO miceCocaine treatmentDiolistic labelingSynaptic remodelingBrain slicesBrain areasConstitutive knockoutMature spinesLocomotor activityAcetylcholine 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
2008
Knockout of STriatal enriched protein tyrosine phosphatase in mice results in increased ERK1/2 phosphorylation
Venkitaramani DV, Paul S, Zhang Y, Kurup P, Ding L, Tressler L, Allen M, Sacca R, Picciotto MR, Lombroso PJ. Knockout of STriatal enriched protein tyrosine phosphatase in mice results in increased ERK1/2 phosphorylation. Synapse 2008, 63: 69-81. PMID: 18932218, PMCID: PMC2706508, DOI: 10.1002/syn.20608.Peer-Reviewed Original ResearchConceptsSTEP knockout miceStriatal enriched protein tyrosine phosphataseKnockout miceWild-type miceERK1/2 activityHomozygous knockout miceBrain-specific proteinsExtracellular signal-regulated kinase1/2Wild-type controlsCA2 regionKO miceSTEP protein levelsLateral nucleusCytoarchitectural abnormalitiesSynaptic stimulationCultured neuronsSynaptic plasticityMice resultsHeterozygous miceMiceERK1/2 phosphorylationProtein tyrosine phosphataseProtein levelsNicotine-induced plasticity during development: Modulation of the cholinergic system and long-term consequences for circuits involved in attention and sensory processing
Heath CJ, Picciotto MR. Nicotine-induced plasticity during development: Modulation of the cholinergic system and long-term consequences for circuits involved in attention and sensory processing. Neuropharmacology 2008, 56: 254-262. PMID: 18692078, PMCID: PMC2635334, DOI: 10.1016/j.neuropharm.2008.07.020.Peer-Reviewed Original ResearchConceptsDevelopmental nicotine exposureSmoke exposureNicotine exposureEndogenous cholinergic signalingTobacco smoke exposureSensory processingSensory processing deficitsNicotinic acetylcholine receptorsAttention deficit hyperactivity disorderCritical periodDeficit hyperactivity disorderPregnant womenCholinergic systemCholinergic signalingLong-term consequencesEpidemiological studiesAnimal modelsAcetylcholine receptorsSynaptic plasticityNeuropsychiatric conditionsHyperactivity disorderNicotineExposureProcessing deficitsBehavioral processes
2007
Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons
Rao Y, Liu ZW, Borok E, Rabenstein RL, Shanabrough M, Lu M, Picciotto MR, Horvath TL, Gao XB. Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons. Journal Of Clinical Investigation 2007, 117: 4022-4033. PMID: 18060037, PMCID: PMC2104495, DOI: 10.1172/jci32829.Peer-Reviewed Original ResearchConceptsHypocretin/orexin neuronsLong-term potentiationOrexin neuronsGlutamatergic synapsesSynaptic plasticitySleep lossExperience-dependent synaptic plasticityDopamine D1 receptorsChronic sleep lossSleep-wake regulationModafinil treatmentLateral hypothalamusD1 receptorsSimilar potentiationBrain slicesNeuronal activityNeuronal circuitryDopamine systemNervous systemSynaptic strengthNeuronsPathological conditionsGentle handlingMiceWakefulnessA Calcium- and Calmodulin-Dependent Kinase Iα/Microtubule Affinity Regulating Kinase 2 Signaling Cascade Mediates Calcium-Dependent Neurite Outgrowth
Uboha NV, Flajolet M, Nairn AC, Picciotto MR. A Calcium- and Calmodulin-Dependent Kinase Iα/Microtubule Affinity Regulating Kinase 2 Signaling Cascade Mediates Calcium-Dependent Neurite Outgrowth. Journal Of Neuroscience 2007, 27: 4413-4423. PMID: 17442826, PMCID: PMC6672303, DOI: 10.1523/jneurosci.0725-07.2007.Peer-Reviewed Original ResearchConceptsKinase domainNeurite outgrowthNeuronal differentiationCalmodulin-dependent kinase ITwo-hybridNeuro-2a cellsPhosphorylation sitesSignal transductionKinase ICaMKIKinase activityMicrotubule affinityKinase 2Calcium-dependent pathwayCritical regulatorIndependent screensPrimary hippocampal neuronsNovel siteCalcium ionophore ionomycinOutgrowthIonophore ionomycinSynaptic plasticityDifferentiationHippocampal neuronsPhysiological effects
2005
Impaired Synaptic Plasticity and Learning in Mice Lacking β-Adducin, an Actin-Regulating Protein
Rabenstein RL, Addy NA, Caldarone BJ, Asaka Y, Gruenbaum LM, Peters LL, Gilligan DM, Fitzsimonds RM, Picciotto MR. Impaired Synaptic Plasticity and Learning in Mice Lacking β-Adducin, an Actin-Regulating Protein. Journal Of Neuroscience 2005, 25: 2138-2145. PMID: 15728854, PMCID: PMC1352335, DOI: 10.1523/jneurosci.3530-04.2005.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsAvoidance LearningCalmodulin-Binding ProteinsConditioning, ClassicalCytoskeletonDendritesElectroshockFearFemaleFreezing Reaction, CatalepticGyrus CinguliHippocampusLearning DisabilitiesMaleMaze LearningMemory DisordersMiceMice, Inbred C57BLMice, KnockoutMice, Neurologic MutantsNerve Tissue ProteinsNeuronal PlasticityNucleus AccumbensRNA, MessengerConceptsBeta-adducinActin regulating proteinsCAMP-dependent mannerSynaptic plasticityActin cytoskeletonΒ-adducinCytoskeletal organizationPlasma membraneAdducinCellular mechanismsActivity-dependent synaptic plasticitySitu hybridizationPostsynaptic densityProteinPlasticitySpine morphologyImportant roleCytoskeletonSynaptic stimulationFamilyImpaired synaptic plasticityLong-term potentiationMiceMRNAHybridization