2025
Activation of a Potassium Channel Mutation That Causes Spinocerebellar Ataxia Promotes Aggregation of the RhoGEF Domain‐Containing Protein Plekhg4
Zhang Y, Andrawis A, Kaczmarek L. Activation of a Potassium Channel Mutation That Causes Spinocerebellar Ataxia Promotes Aggregation of the RhoGEF Domain‐Containing Protein Plekhg4. The FASEB Journal 2025, 39: e70552. PMID: 40249242, DOI: 10.1096/fj.202402809rr.Peer-Reviewed Original ResearchConceptsGuanine nucleotide exchange factorKv3.3 channelsNucleation of actin filamentsPlasma membraneNucleotide exchange factorPurkinje neuronsRegulating Rac1 activitySpinocerebellar ataxiaPotassium channel mutationsAuditory brainstem neuronsCerebellar Purkinje neuronsActin nucleationPurkinje cell activityWild-type channelsExchange factorActin filamentsPotential new therapeutic approachCytoplasmic proteinsTreatment of spinocerebellar ataxiaRac1 activationHAX-1Cytoplasmic aggregatesRegulate excitabilityBrainstem neuronsCHO cells
2023
Modulation of potassium conductances optimizes fidelity of auditory information
Kaczmarek L. Modulation of potassium conductances optimizes fidelity of auditory information. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2216440120. PMID: 36930599, PMCID: PMC10041146, DOI: 10.1073/pnas.2216440120.Peer-Reviewed Original ResearchConceptsPotassium currentAuditory brainstem neuronsAuditory stimuliHigh-frequency firingGroups of neuronsLow-frequency stimuliBrainstem neuronsHigh-frequency stimuliIntrinsic excitabilityEnsembles of neuronsPostsynaptic neuronsAuditory neuronsNeurotransmitter releaseModulatory mechanismsAuditory stimulationFiring ratePotassium conductanceNeuronsPotassium channelsSingle neuronsAmplitude of currentsLoud soundsEnvironmental sound levelsChannel activityPositive membrane potentials
2021
Modulation of Neuronal Potassium Channels During Auditory Processing
Wu J, Kaczmarek LK. Modulation of Neuronal Potassium Channels During Auditory Processing. Frontiers In Neuroscience 2021, 15: 596478. PMID: 33613177, PMCID: PMC7887315, DOI: 10.3389/fnins.2021.596478.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsPotassium channelsAuditory brainstem neuronsAuditory brainstem nucleiNeuronal potassium channelsAuditory informationBrainstem neuronsBrainstem nucleiCertain neuronsPotassium currentFiring patternsNeuronsGene mutationsAuditory processingAuditory stimuliHigh rateLong-term modulationComplex auditory informationIntrinsic electrical propertiesSuch modulationHuman gene mutationsIntensity of soundAuditory environmentModulation
2017
Pharmacological modulation of Kv3.1 mitigates auditory midbrain temporal processing deficits following auditory nerve damage
Chambers AR, Pilati N, Balaram P, Large CH, Kaczmarek LK, Polley DB. Pharmacological modulation of Kv3.1 mitigates auditory midbrain temporal processing deficits following auditory nerve damage. Scientific Reports 2017, 7: 17496. PMID: 29235497, PMCID: PMC5727503, DOI: 10.1038/s41598-017-17406-x.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAuditory PathwaysAuditory PerceptionCochlear NerveCompulsive BehaviorDisease Models, AnimalImidazolesMembrane Transport ModulatorsMesencephalonMiceModels, BiologicalNeuronsOuabainPyrimidinesRecovery of FunctionShaw Potassium ChannelsTissue Culture TechniquesVestibulocochlear Nerve DiseasesConceptsTemporal processing deficitsAuditory nerve damageCochlear nerve synapsesTemporal sound featuresCentral auditory pathwayAuditory brainstem neuronsPromising therapeutic approachPatch-clamp recordingsOtotoxic drug exposurePrecise temporal codingTemporal firing patternsHigh-threshold channelsVoltage-gated potassium channelsProcessing deficitsNerve damageBrainstem neuronsAfferent inputCentral neuronsDrug exposureAfferent synapsesContralateral earSystemic injectionCompensatory plasticityTherapeutic approachesAuditory cortex
2015
Optogenetic stimulation of cholinergic brainstem neurons during focal limbic seizures: Effects on cortical physiology
Furman M, Zhan Q, McCafferty C, Lerner BA, Motelow JE, Meng J, Ma C, Buchanan GF, Witten IB, Deisseroth K, Cardin JA, Blumenfeld H. Optogenetic stimulation of cholinergic brainstem neurons during focal limbic seizures: Effects on cortical physiology. Epilepsia 2015, 56: e198-e202. PMID: 26530287, PMCID: PMC4679683, DOI: 10.1111/epi.13220.Peer-Reviewed Original ResearchConceptsFocal limbic seizuresLimbic seizuresCortical functionBrainstem neuronsCortical dysfunctionFocal temporal lobe seizuresOptogenetic stimulationCortical slow-wave activityDepressed cortical functionSubcortical cholinergic neuronsTemporal lobe seizuresLoss of consciousnessPedunculopontine tegmental nucleusAnesthetized rat modelSlow wave activityCortical gamma activitySleep-like stateCholinergic neuronsFocal seizuresArousal networkCholinergic stimulationTegmental nucleusRat modelCortical physiologySeizuresStress activates the nucleus incertus and modulates plasticity in the hippocampo-medial prefrontal cortical pathway
Rajkumar R, Wu Y, Farooq U, Tan W, Dawe G. Stress activates the nucleus incertus and modulates plasticity in the hippocampo-medial prefrontal cortical pathway. Brain Research Bulletin 2015, 120: 83-89. PMID: 26529052, DOI: 10.1016/j.brainresbull.2015.10.010.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain StemCatheters, IndwellingCold TemperatureDisease Models, AnimalElectrodes, ImplantedFluorescent Antibody TechniqueHippocampusLong-Term PotentiationMaleNeural PathwaysNeuronsNeurotransmitter AgentsPrefrontal CortexProto-Oncogene Proteins c-fosPyrimidinesPyrrolesRats, Sprague-DawleyReceptors, Corticotropin-Releasing HormoneStress, PsychologicalSwimmingConceptsLong-term potentiationNucleus incertusCRF1 receptorCortical pathwaysStress-responsive circuitsStress-induced suppressionHigh-frequency stimulationCRF1 receptor antagonistsC-fos expressionElevation stressStress-related impairmentBrainstem neuronsReceptor antagonistFrequency stimulationSwim stressRodent brainAntalarminReceptorsPathway
2012
Gradients and Modulation of K+ Channels Optimize Temporal Accuracy in Networks of Auditory Neurons
Kaczmarek LK. Gradients and Modulation of K+ Channels Optimize Temporal Accuracy in Networks of Auditory Neurons. PLOS Computational Biology 2012, 8: e1002424. PMID: 22438799, PMCID: PMC3305353, DOI: 10.1371/journal.pcbi.1002424.Peer-Reviewed Original ResearchConceptsSpontaneous activityPotassium currentRandom spontaneous activityAuditory brainstem neuronsAuditory brainstem nucleiSubset of neuronsMaximal firing rateHigh rateNormal auditory processingPattern of stimulationBrainstem neuronsBrainstem nucleiSynaptic outputAuditory neuronsChannel expressionSuch neuronsStimulus rateAction potentialsTonotopic axisSound stimulationFiring ratePotassium conductanceNeuronsKv3 channelsIndividual neurons
2005
Acoustic environment determines phosphorylation state of the Kv3.1 potassium channel in auditory neurons
Song P, Yang Y, Barnes-Davies M, Bhattacharjee A, Hamann M, Forsythe ID, Oliver DL, Kaczmarek LK. Acoustic environment determines phosphorylation state of the Kv3.1 potassium channel in auditory neurons. Nature Neuroscience 2005, 8: 1335-1342. PMID: 16136041, DOI: 10.1038/nn1533.Peer-Reviewed Original ResearchMeSH KeywordsAcoustic StimulationAction PotentialsAnimalsAnimals, NewbornBrain StemCHO CellsCricetinaeCricetulusDose-Response Relationship, RadiationElectric StimulationEnzyme InhibitorsFunctional LateralityGene Expression RegulationImmunohistochemistryIn Vitro TechniquesIndolesMaleimidesNeuronsPatch-Clamp TechniquesPhosphorylationProtein Kinase CRatsRats, Sprague-DawleyTetradecanoylphorbol AcetateConceptsKv3.1 potassium channelAction potentialsAuditory neuronsPotassium channelsShort-duration action potentialsRat brainstem neuronsAuditory brainstem nucleiProtein kinase CHigh-frequency spikingHigh-frequency auditoryBrainstem neuronsHigh-frequency stimuliBrainstem nucleiSynaptic stimulationNeuronsInteraural differencesSound localizationIntrinsic electrical propertiesKinase C
2004
Loss of Kv3.1 Tonotopicity and Alterations in cAMP Response Element-Binding Protein Signaling in Central Auditory Neurons of Hearing Impaired Mice
von Hehn CA, Bhattacharjee A, Kaczmarek LK. Loss of Kv3.1 Tonotopicity and Alterations in cAMP Response Element-Binding Protein Signaling in Central Auditory Neurons of Hearing Impaired Mice. Journal Of Neuroscience 2004, 24: 1936-1940. PMID: 14985434, PMCID: PMC6730406, DOI: 10.1523/jneurosci.4554-03.2004.Peer-Reviewed Original ResearchMeSH KeywordsAcoustic StimulationAge FactorsAnimalsAuditory PathwaysBrain StemCerebellumCyclic AMP Response Element-Binding ProteinDisease ProgressionMaleMiceMice, Inbred C57BLMice, Inbred CBAMice, Inbred DBANeuronsNeuropeptidesPhosphorylationPotassium ChannelsPotassium Channels, Voltage-GatedPresbycusisReflex, StartleShaw Potassium ChannelsConceptsCAMP response element-binding proteinResponse element-binding proteinTonotopic axisBL/6 miceElement-binding proteinCochlear hair cell lossPCREB-positive cellsAuditory brainstem neuronsCentral auditory neuronsHair cell lossCBA/JTranscription factor cAMP response element-binding proteinBrainstem neuronsKv3.1 potassium channel geneTrapezoid bodyImpaired miceMedial nucleusAuditory brainstemImmunopositive cellsAuditory neuronsMedial endPotassium channel genesGood hearingCell lossCREB expression
1997
Neuronal and Non-Neuronal Collapsin-1 Binding Sites in Developing Chick Are Distinct from Other Semaphorin Binding Sites
Takahashi T, Nakamura F, Strittmatter S. Neuronal and Non-Neuronal Collapsin-1 Binding Sites in Developing Chick Are Distinct from Other Semaphorin Binding Sites. Journal Of Neuroscience 1997, 17: 9183-9193. PMID: 9364065, PMCID: PMC6573609, DOI: 10.1523/jneurosci.17-23-09183.1997.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAvian ProteinsAxonsBinding SitesCells, CulturedCentral Nervous SystemChick EmbryoDNA, ComplementaryFetal ProteinsGanglia, SpinalGlycoproteinsLungMembrane ProteinsMesodermMiceMotor NeuronsMultigene FamilyNerve Growth FactorsNerve Tissue ProteinsNeuronsNeurotrophin 3Organ SpecificityRatsRats, Sprague-DawleyReceptors, Cell SurfaceRecombinant Fusion ProteinsSemaphorin-3AConceptsFusion proteinBinding sitesGrowth conesDRG neuronsNon-neuronal tissuesExtracellular proteinsF fusion proteinSemaphorin familyDRG growth conesProteinLow nanomolar affinityMajor blood vesselsLigand familyBrainstem neuronsSympathetic neuronsNanomolar affinityNervous systemAxonal pathsBiological activityBlood vesselsNeuronsFamilySitesMesenchymeSemaphorins
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