The Study on Modulation by the MOC System on Cochlear Amplification at the Early Stage of Hearing Development

LIN Guotong; ZHANG Yu; SONG Lei

doi:10.3969/j.issn.1672-2922.2024.05.022

Abstract：Objective To investigate the impact of cochlear efferent innervation on hearing development,especially Prestin levels and cochlear frequency coding,using acetylcholine receptor α9 subunit knockout(Chrna9 KO)and functional knock-in point-mutant(Chrna9 KI)mice.Methods α9 KO and KI mice and normal control mice aged p1 8 received Auditory brainstem responses(ABRs)evaluation.Distortion product otoacoustic emission(DPOAE)group delay was measured to assess frequency place coding on the basilar membrane.The morphology of efferent synapses and ribbon synapses were examined by immunofluorescence staining.Whole-cell patch clamps were used to evaluate the function of outer hair cells(OHCs)and Prestin expression by measuring nonlinear capacitance.Results There were no significant differences in ABR thresholds between α9 KO,KI mice and normal controls from 4.0 kHz to 45.0 kHz(P＞0.05).ABR wave Ⅰ amplitudes at 22.6,16 and 8 kHz were higher in KI Homo mice than in normal controls at 80-90 dB SPL(P＜0.05),but not between KO Homo mice and normal controls(P＞0.05).DPOAE group delay was shorter in KI Homo mice than in KI WT mice at 60 dB SPL for f2=13 kHz(left panel)(P＜0.05),but not between KO Homo and normal controls(P＞0.05).Compared with KI WT mice,the efferent MOC terminals only slightly increased in the first and third rows of OHCs in the apical turn(P＜0.05)in KI Homo mice,and showed no difference in the middle and basal turns(P＞0.05).The MOC efferent terminals significantly decreased in all three rows of OHCs in the apical and middle turns,and slightly in the third row OHCs in the basal turn in KO Homo mice,compared with KO WT mice(P＜0.05).Typical NLC curves for OHCs and derived parameters showed no statistical difference among the three groups(P＜0.05).Conclusion Upon completion of peripheral auditory development,reduction of efferent(Chrna9 KO)innervations does not affect hearing thresholds,ribbon synapse counts and OHC electromotility.However,enhanced efferent modulation(Chrna9 KI)may functionally alter traveling wave and frequency place map in the organ of Corti.