2022
Hippocampal 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
2020
Converging 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 mice
2017
Bidirectional Regulation of Aggression in Mice by Hippocampal Alpha-7 Nicotinic Acetylcholine Receptors
Lewis AS, Pittenger ST, Mineur YS, Stout D, Smith PH, Picciotto MR. Bidirectional Regulation of Aggression in Mice by Hippocampal Alpha-7 Nicotinic Acetylcholine Receptors. Neuropsychopharmacology 2017, 43: 1267-1275. PMID: 29114104, PMCID: PMC5916354, DOI: 10.1038/npp.2017.276.Peer-Reviewed Original ResearchConceptsΑ7 nAChRsDentate gyrusNicotinic acetylcholine receptorsGTS-21Resident-intruder interactionsAlpha 7 nicotinic acetylcholine receptorAcetylcholine receptorsΑ7 nicotinic acetylcholine receptorExcitatory-inhibitory balancePromising therapeutic interventionGranule cell activityAggressive behaviorResident-intruder testHippocampal α7Wild-type controlsUnderlying neurobiological substratesGABAergic interneuronsMale micePotential neural circuitsRegulation of aggressionGranule cellsTherapeutic interventionsPartial agonistBrain regionsCell activityHippocampal α7 nicotinic ACh receptors contribute to modulation of depression‐like behaviour in C57BL/6J mice
Mineur YS, Mose TN, Blakeman S, Picciotto MR. Hippocampal α7 nicotinic ACh receptors contribute to modulation of depression‐like behaviour in C57BL/6J mice. British Journal Of Pharmacology 2017, 175: 1903-1914. PMID: 28264149, PMCID: PMC5979617, DOI: 10.1111/bph.13769.Peer-Reviewed Original ResearchConceptsDepression-like behaviorNicotinic ACh receptorsFemale miceMale miceCholinergic signalingACh receptorsΑ7 nAChRsSignificant antidepressant-like effectΑ7 nicotinic ACh receptorsEffect of α7Antidepressant-like effectsAgonist GTS-21Depression-related behaviorsC-Fos immunoreactivityACh receptor antagonistDepression-like phenotypeAnxiety-like behaviorNicotinic acetylcholine receptorsAnxiety-like phenotypeHippocampal α7Physostigmine administrationAntagonist methyllycaconitineReceptor antagonistSwim testGTS-21
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
2014
Expression of the 5-HT1A Serotonin Receptor in the Hippocampus Is Required for Social Stress Resilience and the Antidepressant-Like Effects Induced by the Nicotinic Partial Agonist Cytisine
Mineur YS, Einstein EB, Bentham MP, Wigestrand MB, Blakeman S, Newbold SA, Picciotto MR. Expression of the 5-HT1A Serotonin Receptor in the Hippocampus Is Required for Social Stress Resilience and the Antidepressant-Like Effects Induced by the Nicotinic Partial Agonist Cytisine. Neuropsychopharmacology 2014, 40: 938-946. PMID: 25288485, PMCID: PMC4330507, DOI: 10.1038/npp.2014.269.Peer-Reviewed Original ResearchMeSH Keywords8-Hydroxy-2-(di-n-propylamino)tetralinAlkaloidsAnimalsAntidepressive AgentsAzocinesDisease Models, AnimalDrug SynergismFluoxetineGene Expression RegulationHEK293 CellsHindlimb SuspensionHippocampusHumansInterpersonal RelationsMaleMiceMice, Inbred C57BLMotor ActivityQuinolizinesReceptor, Serotonin, 5-HT1ASelective Serotonin Reuptake InhibitorsSerotonin Receptor AgonistsStress, PsychologicalConceptsAntidepressant-like effectsSelective serotonin reuptake inhibitorsDorsal rapheCholinergic systemAgonist cytisineNicotinic acetylcholine receptor blockersEffects of cytisineTreatment-resistant patientsSerotonin reuptake inhibitorsAcetylcholine receptor blockerSSRI fluoxetineReceptor blockersAntidepressant efficacyReuptake inhibitorsSerotonin depletionCholinergic drugsMood disordersSerotonin receptorsMouse modelPharmacological approachesHippocampusReceptorsCytisineRapheMolecular mechanisms
2013
Cholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior
Mineur YS, Obayemi A, Wigestrand MB, Fote GM, Calarco CA, Li AM, Picciotto MR. Cholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 3573-3578. PMID: 23401542, PMCID: PMC3587265, DOI: 10.1073/pnas.1219731110.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholinesteraseAnimalsAntidepressive AgentsAnxietyBehavior, AnimalCholinergic AntagonistsCholinergic NeuronsDependovirusDepressionFluoxetineGene Knockdown TechniquesHindlimb SuspensionHippocampusHumansMaleMiceMice, Inbred C57BLPhenotypePhysostigmineReceptors, CholinergicResilience, PsychologicalRNA, Small InterferingSignal TransductionStress, PsychologicalTime FactorsConceptsDepression-like behaviorShRNA-mediated knockdownSelective serotonin reuptake inhibitor fluoxetineSerotonin reuptake inhibitor fluoxetineAChE inhibitor physostigmineAdministration of fluoxetineBlockade of acetylcholinesteraseEndophenotypes of depressionHippocampal AChE activityAntidepressant-like effectsReuptake inhibitor fluoxetineAChE activityDepression-like phenotypeSymptoms of depressionSocial defeat paradigmHippocampal AChEMuscarinic antagonistCholinergic drugsInhibitor physostigmineCholinergic systemClinical trialsSystemic administrationMood disordersSystemic effectsAnimal models
2011
Striatal‐enriched protein tyrosine phosphatase (STEP) knockout mice have enhanced hippocampal memory
Venkitaramani DV, Moura PJ, Picciotto MR, Lombroso PJ. Striatal‐enriched protein tyrosine phosphatase (STEP) knockout mice have enhanced hippocampal memory. European Journal Of Neuroscience 2011, 33: 2288-2298. PMID: 21501258, PMCID: PMC3118976, DOI: 10.1111/j.1460-9568.2011.07687.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalFocal Adhesion Kinase 2HippocampusMemoryMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PhosphorylationProtein Tyrosine Phosphatases, Non-ReceptorReceptors, AMPAReceptors, N-Methyl-D-AspartateSynaptic TransmissionConceptsStriatal-enriched protein tyrosine phosphataseSTEP KO miceProtein tyrosine phosphataseBrain-specific phosphataseProline-rich tyrosine kinaseEffect of deletionN-methyl-D-aspartate receptorsERK1/2 substratesNR1/NR2B N‐Methyl‐d‐Aspartate ReceptorsPotential molecular mechanismsTyrosine phosphataseSignaling proteinsTyrosine phosphorylationDownstream effectorsKinase 1/2Molecular mechanismsTyrosine kinaseFunctional importanceKnockout micePhosphorylationSTEP knockout miceSynaptic strengtheningIsoxazole propionic acid (AMPA) receptorsSynaptosomal expressionRegulation
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 levels
2007
A 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
2004
High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation
Caldarone BJ, Harrist A, Cleary MA, Beech RD, King SL, Picciotto MR. High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation. Biological Psychiatry 2004, 56: 657-664. PMID: 15522249, DOI: 10.1016/j.biopsych.2004.08.010.Peer-Reviewed Original ResearchMeSH KeywordsAmitriptylineAnalysis of VarianceAnimalsAntidepressive Agents, TricyclicBehavior, AnimalBromodeoxyuridineCell CountCell ProliferationDose-Response Relationship, DrugDrosophila ProteinsDrug InteractionsHelplessness, LearnedHindlimb SuspensionHippocampusImmunohistochemistryMecamylamineMiceMice, Inbred C57BLMice, KnockoutNeuronsNicotinic AntagonistsNortriptylineReceptors, NicotinicSwimmingConceptsHigh-affinity nAChRsHippocampal cell proliferationNicotinic acetylcholine receptorsSwim testAcetylcholine receptorsCell proliferationHigh-affinity nicotinic acetylcholine receptorsNoncompetitive nAChR antagonist mecamylamineAntagonism of nAChRsAntidepressant-induced increasesAntidepressant-like effectsNAChR antagonist mecamylamineWild-type miceInhibition of nAChRsAntidepressants actAntidepressant actionAntidepressant effectsChronic treatmentAntagonist mecamylamineAntidepressant propertiesTricyclic antidepressantsAntidepressant activityTherapeutic effectKnockout miceNoncompetitive antagonistAlteration of hippocampal cell proliferation in mice lacking the β2 subunit of the neuronal nicotinic acetylcholine receptor
Harrist A, Beech RD, King SL, Zanardi A, Cleary MA, Caldarone BJ, Eisch A, Zoli M, Picciotto MR. Alteration of hippocampal cell proliferation in mice lacking the β2 subunit of the neuronal nicotinic acetylcholine receptor. Synapse 2004, 54: 200-206. PMID: 15472930, DOI: 10.1002/syn.20081.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsHippocampal cell proliferationAcetylcholine receptorsCell proliferationNeuronal nicotinic acetylcholine receptorsNeurotrophic factor BDNFAdult hippocampal neurogenesisHippocampus of miceAge-matched controlsGranule cell layerCellular proliferationPlasma corticosterone levelsHippocampal-dependent tasksGranule cell proliferationHippocampal proliferationHippocampal neurogenesisEndogenous acetylcholineAge-related declineDentate gyrusNeuronal survivalAbnormal myelinationCorticosterone levelsNormal agingYoung adultsApoptotic cell death