Featured Publications
Differential outcomes of high‐fat diet on age‐related rescaling of cochlear frequency place coding
Zhang Y, Lin G, Xue N, Wang Y, Du T, Liu H, Xiong W, Shang W, Wu H, Song L. Differential outcomes of high‐fat diet on age‐related rescaling of cochlear frequency place coding. The FASEB Journal 2023, 37: e23167. PMID: 37651093, DOI: 10.1096/fj.202300457rr.Peer-Reviewed Original ResearchConceptsAge-related hearing lossHigh-fat dietHearing lossEffects of HFDLoss of OHCsActivation of TRPV1Sensorineural hearing lossCBA/CaJPlace codingCochlear frequency selectivityTRPV1 expressionOHC functionInflammatory responseCommon causeHFD cohortGenetic backgroundYounger ageArachidonic acidCochlear lengthHair cellsPrestin levelsLipid homeostasisRescuing effectCochlear amplificationAge
2024
DMXL2 Is Required for Endocytosis and Recycling of Synaptic Vesicles in Auditory Hair Cells
Peng H, Wang L, Gao Y, Liu H, Lin G, Kong Y, Xu P, Liu H, Yuan Q, Liu H, Song L, Yang T, Wu H. DMXL2 Is Required for Endocytosis and Recycling of Synaptic Vesicles in Auditory Hair Cells. Journal Of Neuroscience 2024, 44: e1405232024. PMID: 39147590, PMCID: PMC11411588, DOI: 10.1523/jneurosci.1405-23.2024.Peer-Reviewed Original ResearchEndocytic membrane retrievalSynaptic vesiclesSynaptic exocytosisMembrane retrievalEndocytic compartmentsMolecular machineryRecycling of synaptic vesiclesReserve poolMembrane capacitance measurementsRibbon synapses of inner hair cellsElectron microscopy reconstructionsAuditory synaptopathyMutant miceSynaptic endocytosisCell-specific knockout miceHuman homologMembrane-proximalHair cellsAuditory hair cellsMolecular basisEndocytosisRibbon synapsesInner hair cellsHearing lossDMXL2Revisiting the Potency of Tbx2 Expression in Transforming Outer Hair Cells into Inner Hair Cells at Multiple Ages In Vivo
Bi Z, Ren M, Zhang Y, He S, Song L, Li X, Liu Z. Revisiting the Potency of Tbx2 Expression in Transforming Outer Hair Cells into Inner Hair Cells at Multiple Ages In Vivo. Journal Of Neuroscience 2024, 44: e1751232024. PMID: 38688721, PMCID: PMC11154855, DOI: 10.1523/jneurosci.1751-23.2024.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
Functional 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 alterationsCellular Differences in the Cochlea of CBA and B6 Mice May Underlie Their Difference in Susceptibility to Hearing Loss
Liu H, Li G, Lu J, Gao Y, Song L, Li G, Wu H. Cellular Differences in the Cochlea of CBA and B6 Mice May Underlie Their Difference in Susceptibility to Hearing Loss. Frontiers In Cellular Neuroscience 2019, 13: 60. PMID: 30873008, PMCID: PMC6400987, DOI: 10.3389/fncel.2019.00060.Peer-Reviewed Original ResearchInner hair cellsEarly-onset hearing lossB6 miceOnset hearing lossHearing lossRibbon synapsesOuter hair cell functionMouse strainsCBA/CaJ miceWave I latencySpiral ganglion neuronsSynaptic vesiclesHair cell functionCellular differencesStable hearingSimilar hearing thresholdsI latencyABR thresholdGanglion neuronsGlutamate toxicityHearing thresholdsWave IMiceHair cellsCell function
2018
Characterizing 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
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 latency
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
2011
Chloride Dependent Coupling of Molecular to Cellular Mechanics in the Outer Hair Cell of Corti's Organ
Song L, Santos-Sacchi J, Shera C, Olson E. Chloride Dependent Coupling of Molecular to Cellular Mechanics in the Outer Hair Cell of Corti's Organ. AIP Conference Proceedings 2011, 1403: 179-184. DOI: 10.1063/1.3658083.Peer-Reviewed Original ResearchCellular mechanicsConformational changesMotor protein prestinProtein prestinMolecular eventsLateral membranesOHC lateral membraneCellular expressionWhole cellsElectromotilityOuter Hair CellsPrestinHair cellsReceptor potentialNonlinear capacitanceMolecular conformational changesIntracellular chloride levelsCellsTight couplingOrgansOHC receptor potentialsExpressionMembraneNormal levelsVivo
2010
Effect of capsaicin on potassium conductance and electromotility of the guinea pig outer hair cell
Wu T, Song L, Shi X, Jiang Z, Santos-Sacchi J, Nuttall A. Effect of capsaicin on potassium conductance and electromotility of the guinea pig outer hair cell. Hearing Research 2010, 272: 117-124. PMID: 21044673, PMCID: PMC3387680, DOI: 10.1016/j.heares.2010.10.010.Peer-Reviewed Original ResearchConceptsOuter hair cellsTRPV-1 channelsHair cellsPrimary sensory neuronsEffects of capsaicinGuinea pig outer hair cellsSensory neuronsPharmacological actionsCapsaicinPotassium conductancePotent blockerPharmacological propertiesDirect actionNovel actionCochlear amplificationK conductanceAuditory effectsClassic activatorAuditory receptionCellsNociceptionElectromotilityBlockersNew findingsNeuronsCombinatorial Cysteine Mutagenesis Reveals a Critical Intramonomer Role for Cysteines in Prestin Voltage Sensing
Bai JP, Surguchev A, Bian S, Song L, Santos-Sacchi J, Navaratnam D. Combinatorial Cysteine Mutagenesis Reveals a Critical Intramonomer Role for Cysteines in Prestin Voltage Sensing. Biophysical Journal 2010, 99: 85-94. PMID: 20655836, PMCID: PMC2895379, DOI: 10.1016/j.bpj.2010.03.066.Peer-Reviewed Original ResearchConceptsDisulfide bond formationCysteine residuesCysteine residue pairsSingle cysteine residueCysteine mutagenesisTransmembrane proteinSubstitution mutantsSLC26 familyResidue pairsFörster resonance energy transferCharge movementVoltage-dependent charge movementDisulfide interactionsResonance energy transferPrestinProteinMutantsDimer formationResiduesCysteineHair cellsSurface expressionAnion transportersCochlear amplificationWestern blot