Featured Publications
Prestin derived OHC surface area reduction underlies age‐related rescaling of frequency place coding
Zhang Y, Lin G, Wang Y, Xue N, Lin X, Du T, Xiong W, Song L. Prestin derived OHC surface area reduction underlies age‐related rescaling of frequency place coding. Hearing Research 2021, 423: 108406. PMID: 34933788, DOI: 10.1016/j.heares.2021.108406.Peer-Reviewed Original Research
2023
In situ regeneration of inner hair cells in the damaged cochlea by temporally regulated co-expression of Atoh1 and Tbx2
Li X, Ren M, Gu Y, Zhu T, Zhang Y, Li J, Li C, Wang G, Song L, Bi Z, Liu Z. In situ regeneration of inner hair cells in the damaged cochlea by temporally regulated co-expression of Atoh1 and Tbx2. Development 2023, 150 PMID: 38078650, DOI: 10.1242/dev.201888.Peer-Reviewed Original ResearchCochlear transcript diversity and its role in auditory functions implied by an otoferlin short isoform
Liu H, Liu H, Wang L, Song L, Jiang G, Lu Q, Yang T, Peng H, Cai R, Zhao X, Zhao T, Wu H. Cochlear transcript diversity and its role in auditory functions implied by an otoferlin short isoform. Nature Communications 2023, 14: 3085. PMID: 37248244, PMCID: PMC10227054, DOI: 10.1038/s41467-023-38621-3.Peer-Reviewed Original ResearchConceptsShort isoformEndocytic membrane retrievalRNA sequencing techniquesDiverse biological functionsInner hair cellsTranscript diversityUnannotated transcriptsRNA-seqAlternative isoformsMembrane retrievalBiological functionsGENCODE databasesKey proteinsIsoform resolutionSequencing techniquesSustained exocytosisIsoformsMechanistic understandingAuditory functionSanger sequencingHair cellsTranscriptsRT-PCRSynaptic transmissionAuditory phenotype
2022
Outer hair cell function is normal in βV spectrin knockout mice
Stankewich MC, Bai JP, Stabach PR, Khan S, Tan WJT, Surguchev A, Song L, Morrow JS, Santos-Sacchi J, Navaratnam DS. Outer hair cell function is normal in βV spectrin knockout mice. Hearing Research 2022, 423: 108564. PMID: 35864018, DOI: 10.1016/j.heares.2022.108564.Peer-Reviewed Original ResearchConceptsOuter hair cellsAuditory brainstem response wavesAuditory thresholdOuter hair cell functionSpiral ganglion neuronsEfferent nerve fibersHair cell functionNumber of afferentsGanglion neuronsNerve fibersKnockout miceNeuronal structuresMiceHair cellsCell functionElectromechanical activityPutative roleType IOngoing investigationExon deletionsSynaptopathyAfferentsData supportResponse wavesNeuronsPrestin-Mediated Frequency Selectivity Does not Cover Ultrahigh Frequencies in Mice
Li J, Liu S, Song C, Zhu T, Zhao Z, Sun W, Wang Y, Song L, Xiong W. Prestin-Mediated Frequency Selectivity Does not Cover Ultrahigh Frequencies in Mice. Neuroscience Bulletin 2022, 38: 769-784. PMID: 35279808, PMCID: PMC9276951, DOI: 10.1007/s12264-022-00839-4.Peer-Reviewed Original ResearchConceptsOuter hair cellsCation channel blockerCochlear outer hair cellsPrestin knockout miceAudiometric measurementsChannel blockersPharmacogenetic manipulationCochlear sensitivityMiceSpecific ablationHair cellsTarget cellsBehavior testsHearingMembrane potentialLow-pass featureAblationUltrasonic hearingCellsPrestinBlockersMembrane resonanceIn vivo CRISPR‐Cas9‐mediated DNA chop identifies a cochlear outer hair cell‐specific enhancer
Sun Y, Zhang Y, Zhang D, Wang G, Song L, Liu Z. In vivo CRISPR‐Cas9‐mediated DNA chop identifies a cochlear outer hair cell‐specific enhancer. The FASEB Journal 2022, 36: e22233. PMID: 35225354, DOI: 10.1096/fj.202100421rr.Peer-Reviewed Original ResearchConceptsDNA fragment deletionKbp fragmentKbp segmentFragment deletionCell-specific enhancerOuter hair cellsLarge DNA fragment deletionGreen fluorescent proteinCRISPR/Motor proteinsIntron regionsGene therapeutic applicationsFluorescent proteinDifferent speciesCochlear outer hair cellsBp fragmentEnhancerSLC26A5Hair cellsEGFPProteinTransgenic miceDeletionKbpPrestin expression
2021
Genes related to SNPs identified by Genome-wide association studies of age-related hearing loss show restriction to specific cell types in the adult mouse cochlea
Xue N, Song L, Song Q, Santos-Sacchi J, Wu H, Navaratnam D. Genes related to SNPs identified by Genome-wide association studies of age-related hearing loss show restriction to specific cell types in the adult mouse cochlea. Hearing Research 2021, 410: 108347. PMID: 34536825, DOI: 10.1016/j.heares.2021.108347.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingApical cell polarityGenome-wide association studiesAdult mouse cochleaSpecific cell typesCell polaritySubtypes of cellsSignificant genetic componentSingle nucleotide polymorphismsVesicle recyclingRNA sequencingAssociation studiesGenesVarying ExpressionCell typesGenetic componentNucleotide polymorphismsSNPsMouse cochleaCell functionGenesetsHair cellsHair cell functionSignificant overlapExpression
2020
Down-regulation of AMPK signaling pathway rescues hearing loss in TFB1 transgenic mice and delays age-related hearing loss
Zhao J, Li G, Zhao X, Lin X, Gao Y, Raimundo N, Li G, Shang W, Wu H, Song L. Down-regulation of AMPK signaling pathway rescues hearing loss in TFB1 transgenic mice and delays age-related hearing loss. Aging 2020, 12: 5590-5611. PMID: 32240104, PMCID: PMC7185105, DOI: 10.18632/aging.102977.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesPro-survival functionRole of AMPKRegulation of AMPKActivation of AMPKAnti-apoptotic signalingPro-apoptotic signalingProtein kinaseOuter hair cellsAMPK activationAMPK hyperactivationROS-AMPKSpiral ganglion neuronsAMPK downregulationApoptosis pathwayHair cell synapsesAMPKMitochondrial dysfunctionCochlear tissuesCell growthRedox imbalanceBcl2 pathwayInner hair cell synapsesOxygen speciesHair cellsMaturation of Voltage-induced Shifts in SLC26a5 (Prestin) Operating Point during Trafficking and Membrane Insertion
Zhai F, Song L, Bai JP, Dai C, Navaratnam D, Santos-Sacchi J. Maturation of Voltage-induced Shifts in SLC26a5 (Prestin) Operating Point during Trafficking and Membrane Insertion. Neuroscience 2020, 431: 128-133. PMID: 32061780, PMCID: PMC8720582, DOI: 10.1016/j.neuroscience.2020.02.003.Peer-Reviewed Original ResearchConceptsMembrane motor proteinVoltage-dependent proteinsMembrane insertionOuter hair cellsMotor proteinsPrestin densityHEK cell linesConformational changesBiophysical forcesOHC electromotilityProteinCell linesMembrane potentialCooperative interactionsPrestinHair cellsCochlear amplificationTransmembrane voltageNonlinear capacitanceMammalsTraffickingVoltage-induced shiftElectromotilityMaturationMembrane
2019
Hearing consequences in Gjb2 knock-in mice: implications for human p.V37I mutation
Lin X, Li G, Zhang Y, Zhao J, Lu J, Gao Y, Liu H, Li G, Yang T, Song L, Wu H. Hearing consequences in Gjb2 knock-in mice: implications for human p.V37I mutation. Aging 2019, 11: 7416-7441. PMID: 31562289, PMCID: PMC6782001, DOI: 10.18632/aging.102246.Peer-Reviewed Original ResearchConceptsHomozygous miceLate-onset progressive hearing lossV37I mutationABR wave I latencySpiral ganglion neuron lossOuter hair cell functionSignificant hair cell lossMiddle ear injectionStria vascularis atrophyWave I latencyABR threshold elevationsProgressive hearing lossHair cell lossHair cell functionEnvironmental insultsI latencyNeuron lossCochlear pathologyHearing lossEar injectionMouse modelCell lossNoise exposureSystemic applicationThreshold elevationFunctional alteration of ribbon synapses in inner hair cells by noise exposure causing hidden hearing loss
Liu H, Lu J, Wang Z, Song L, Wang X, Li G, Wu H. Functional alteration of ribbon synapses in inner hair cells by noise exposure causing hidden hearing loss. Neuroscience Letters 2019, 707: 134268. PMID: 31103727, DOI: 10.1016/j.neulet.2019.05.022.Peer-Reviewed Original ResearchConceptsInner hair cellsModerate noise exposureHearing lossRibbon synapsesNoise exposureHair cellsPersistent reductionWhole-cell patch-clamp recordingsNoise-induced hearing lossSynapse functionAuditory afferent fibersHidden hearing lossABR wave ISynaptic vesiclesAuditory brainstem response (ABR) amplitudesPatch-clamp recordingsSevere noise exposureWhole mount immunofluorescence stainingPatch-clamp electrophysiologySensory hair cellsAfferent fibersABR thresholdPersistent alterationsExposure altersFunctional alterationsModulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice
El-Hassar L, Song L, Tan WJT, Large CH, Alvaro G, Santos-Sacchi J, Kaczmarek LK. Modulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice. Journal Of Neuroscience 2019, 39: 4797-4813. PMID: 30936239, PMCID: PMC6561694, DOI: 10.1523/jneurosci.0839-18.2019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAuditory PathwaysAuditory PerceptionBrain StemCochlear NucleusElectrophysiological PhenomenaEvoked Potentials, Auditory, Brain StemFemaleFragile X Mental Retardation ProteinFragile X SyndromeHydantoinsIn Vitro TechniquesMaleMiceMice, KnockoutPatch-Clamp TechniquesPyridinesShaw Potassium ChannelsConceptsAuditory brainstem responseWild-type animalsRepetitive firingABR wave ICurrent-clamp recordingsAuditory brainstem nucleiVoltage-clamp recordingsHigh-frequency firingSingle action potentialFragile X syndromeTrapezoid bodyBrainstem nucleiBrainstem responseMedial nucleusAuditory brainstemAuditory nerveWave IWave IVAction potentialsSensory stimuliKv3.1 channelsCentral processingMental retardation proteinHigh sound levelsMice
2018
Simultaneous zygotic inactivation of multiple genes in mouse through CRISPR/Cas9-mediated base editing
Zhang H, Pan H, Zhou C, Wei Y, Ying W, Li S, Wang G, Li C, Ren Y, Li G, Ding X, Sun Y, Li G, Song L, Li Y, Yang H, Liu Z. Simultaneous zygotic inactivation of multiple genes in mouse through CRISPR/Cas9-mediated base editing. Development 2018, 145: dev168906. PMID: 30275281, DOI: 10.1242/dev.168906.Peer-Reviewed Original ResearchConceptsGene functionMultiple genesHair cell generationProtein-coding sequencesMulti-gene interactionsModel organismsFunctional genesZygotic mutationsGene crucialHigh-throughput screeningBase editingMouse mutantsStop codonSingle mutationGenesCRISPRCell generationGenetic mutationsMutationsMouse breedingNormal hearing functionDrosophilaMutantsBreedingCodonCharacterizing a novel vGlut3-P2A-iCreER knockin mouse strain in cochlea
Li C, Shu Y, Wang G, Zhang H, Lu Y, Li X, Li G, Song L, Liu Z. Characterizing a novel vGlut3-P2A-iCreER knockin mouse strain in cochlea. Hearing Research 2018, 364: 12-24. PMID: 29706463, DOI: 10.1016/j.heares.2018.04.006.Peer-Reviewed Original ResearchMeSH KeywordsAcoustic StimulationAmino Acid Transport Systems, AcidicAnimalsCochleaEvoked Potentials, Auditory, Brain StemFemaleGene Knock-In TechniquesGenes, ReporterGenotypeHair Cells, Auditory, OuterIntegrasesLuminescent ProteinsMaleMice, Inbred C57BLMice, TransgenicNeurogliaPhenotypeReaction TimeReceptors, EstrogenSelective Estrogen Receptor ModulatorsSpiral GanglionTamoxifenTime FactorsConceptsInner hair cellsOuter hair cellsSpiral ganglion neuronsKnockin mouse strainGlia cellsVesicular glutamate transporter 3Mouse strainsHair cellsCochlear outer hair cellsRosa26-LSLVGLUT3 expressionGanglion neuronsVGLUT3Mouse cochleaTransporter 3Negative cellsMouse genetic studiesAntibody stainingTamoxifenUnique expression patternP2/P3Specific cell typesCell typesSitu hybridizationCochlea
2017
Novel Role of the Mitochondrial Protein Fus1 in Protection from Premature Hearing Loss via Regulation of Oxidative Stress and Nutrient and Energy Sensing Pathways in the Inner Ear
Tan WJ, Song L, Graham M, Schettino A, Navaratnam D, Yarbrough WG, Santos-Sacchi J, Ivanova AV. Novel Role of the Mitochondrial Protein Fus1 in Protection from Premature Hearing Loss via Regulation of Oxidative Stress and Nutrient and Energy Sensing Pathways in the Inner Ear. Antioxidants & Redox Signaling 2017, 27: 489-509. PMID: 28135838, PMCID: PMC5564041, DOI: 10.1089/ars.2016.6851.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsAntioxidantsDisease Models, AnimalEar, InnerEvoked Potentials, Auditory, Brain StemGene Knockout TechniquesHearing LossHumansMiceMicroscopy, Electron, TransmissionMitochondriaOxidative StressProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseSignal TransductionSpiral GanglionTOR Serine-Threonine KinasesTumor Suppressor ProteinsConceptsAge-related hearing lossAuditory brainstem responseHearing lossKO miceEndocochlear potentialOxidative stressMitochondrial dysfunctionMitochondrial dysfunction/oxidative stressEnergy sensing pathwaysNovel therapeutic strategiesMolecular mechanismsPremature hearing lossCochlear stria vascularisMajor hearing lossChronic mitochondrial dysfunctionMetabolic etiologyWorldwide epidemicBrainstem responseClinical trialsVascular pathologyTherapeutic strategiesPathological alterationsABR parametersAO treatmentStria vascularis
2015
Auditory Pathology in a Transgenic mtTFB1 Mouse Model of Mitochondrial Deafness
McKay SE, Yan W, Nouws J, Thormann MJ, Raimundo N, Khan A, Santos-Sacchi J, Song L, Shadel GS. Auditory Pathology in a Transgenic mtTFB1 Mouse Model of Mitochondrial Deafness. American Journal Of Pathology 2015, 185: 3132-3140. PMID: 26552864, PMCID: PMC5801480, DOI: 10.1016/j.ajpath.2015.08.014.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsApoptosisDeafnessDisease Models, AnimalDNA, MitochondrialEvoked Potentials, Auditory, Brain StemHair Cells, Auditory, InnerMice, Inbred C57BLMice, KnockoutMice, TransgenicMitochondrial DiseasesMutationOrgan of CortiReaction TimeSignal TransductionSpiral GanglionStria VascularisTranscription FactorsConceptsAMP kinaseReactive oxygen species-mediated activationTranscription factor E2F1A1555G mutationAuditory pathologyHair cellsTFB1MHearing loss phenotypeRRNA geneAMPK-α1AMPK activityProlonged wave I latencyLoss phenotypeMitochondrial pathologyNonsyndromic deafnessTransgenic mouse strainWave I latencySpiral ganglion neuronsProgressive hearing lossMitochondrial deafnessPotential therapeutic valueDNA causeG mutationOuter hair cellsI latencyAn Electrical Inspection of the Subsurface Cisternae of the Outer Hair Cell
Song L, Santos-Sacchi J. An Electrical Inspection of the Subsurface Cisternae of the Outer Hair Cell. Biophysical Journal 2015, 108: 568-577. PMID: 25650924, PMCID: PMC4317539, DOI: 10.1016/j.bpj.2014.12.010.Peer-Reviewed Original Research
2014
Chloride-driven Electromechanical Phase Lags at Acoustic Frequencies Are Generated by SLC26a5, the Outer Hair Cell Motor Protein
Santos-Sacchi J, Song L. Chloride-driven Electromechanical Phase Lags at Acoustic Frequencies Are Generated by SLC26a5, the Outer Hair Cell Motor Protein. Biophysical Journal 2014, 107: 126-133. PMID: 24988347, PMCID: PMC4119270, DOI: 10.1016/j.bpj.2014.05.018.Peer-Reviewed Original ResearchChloride and Salicylate Influence Prestin-dependent Specific Membrane Capacitance SUPPORT FOR THE AREA MOTOR MODEL* * This work was supported, in whole or in part, by National Institutes of Health Grant NIDCD DC00273 (to J. S. S.).
Santos-Sacchi J, Song L. Chloride and Salicylate Influence Prestin-dependent Specific Membrane Capacitance SUPPORT FOR THE AREA MOTOR MODEL* * This work was supported, in whole or in part, by National Institutes of Health Grant NIDCD DC00273 (to J. S. S.). Journal Of Biological Chemistry 2014, 289: 10823-10830. PMID: 24554714, PMCID: PMC4036195, DOI: 10.1074/jbc.m114.549329.Peer-Reviewed Original Research
2013
Patch-Clamp Recordings from Lateral Line Neuromast Hair Cells of the Living Zebrafish
Ricci AJ, Bai JP, Song L, Lv C, Zenisek D, Santos-Sacchi J. Patch-Clamp Recordings from Lateral Line Neuromast Hair Cells of the Living Zebrafish. Journal Of Neuroscience 2013, 33: 3131-3134. PMID: 23407967, PMCID: PMC3684625, DOI: 10.1523/jneurosci.4265-12.2013.Peer-Reviewed Original ResearchConceptsHair cellsSynaptic vesicle releaseNeuromast hair cellsLiving zebrafishBiological discoveryIonic channel activityZebrafishVesicle releaseChannel activityPhysiological activityLateral lineJunctional couplingCellsDetailed understandingPatch-clamp recordingsVestibular peripheryFishNeuromastsActivityDiscoveryFirst recording