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Dynamic changes in hair cell ribbon synapse induced by loss of spiral ganglion neurons in mice

Chinese Medical Journal 2014年第10期127卷 1941-1946页

作者： Yuan Yasheng Chi Fanglu Department of Otolaryngology Eye Ear Nose & Throat HospitalFudan University Shanghai 200031 China Department of Otolaryngology MEEI Harvard Medical SchoolBoston MA 02115 USA (Yuan YS)

Background Previous studies have suggested that primary degeneration of hair cells causes secondary degeneration of spiral ganglion neurons （SGNs）,but the effect of SGN degeneration on hair cells has not been studied.In the adult mouse inner ear ouabain can selectively and permanently induce the degeneration of type 1 SGNs while leaving type 2 SGNs,efferent fibers,and sensory hair cells relatively intact.This study aimed to investigate the dynamic changes in hair cell ribbon synapse induced by loss of SGNs using ouabain application to the round window niche of adult mice.Methods In the analysis,24 CBA/CAJ mice aged 8-10 weeks,were used,of which 6 normal mice were used as the control group.After ouabain application in the round window niche 6 times in an hour,ABR threshold shifts at least 30 dB in the three experimental groups which had six mice for 1-week group,six for 1-month group,and six for 3-month group.All 24 animals underwent function test at 1 week and then immunostaining at 1 week,1 month,and 3 months.Results The loss of neurons was followed by degeneration of postsynaptic specializations at the afferent synapse with hair cells.One week after ouabain treatment,the nerve endings of type 1 SGNs and postsynaptic densities,as measured by Na/K ATPase and PSD-95,were affected but not entirely missing,but their partial loss had consequences for synaptic ribbons that form the presynaptic specialization at the synapse between hair cells and primary afferent neurons.ribbon numbers in inner hair cells decreased （some of them broken and the ribbon number much decreased）,and the arrangement of the synaptic ribbons had undergone a dynamic reorganization：ribbons with or without associated postsynaptic densities moved from their normal location in the basal membrane of the cell to a more apical location and the neural endings alone were also found at more apical locations without associated ribbons.After 1 month,when the neural postsynaptic densities had completed their degeneration,most ribbons were lost and the remain

关键词： auditory neurons hair cells ribbon synapse degeneration

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Aligned Organization of synapses and Mitochondria in Auditory Hair Cells

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Neuroscience Bulletin 2022年第3期38卷 235-248页

作者： Jing Liu Shengxiong Wang Yan Lu Haoyu Wang Fangfang Wang Miaoxin Qiu Qiwei Xie Hua Han Yunfeng Hua National Laboratory of Pattern Recognition Institute of AutomationChinese Academy of SciencesBeijing100190China School of Artificial Intelligence School of Future TechnologyUniversity of Chinese Academy of SciencesBeijing101408China CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai200031China Putuo People’s Hospital Tongji UniversityShanghai200060China Shanghai Institute of Precision Medicine Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai200125China Department of Otolaryngology-Head and Neck Surgery Shanghai Ninth People’s HospitalShanghai200125China Ear Institute Shanghai Jiao Tong University School of MedicineShanghai200125China Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases Shanghai200125China Research Base of Beijing Modern Manufacturing Development Beijing University of TechnologyBeijing100124China

Recent studies have revealed great functional and structural heterogeneity in the ribbon-type synapses at the basolateral pole of the isopotential inner hair cell(IHC).This feature is believed to be critical for audition over a wide dynamic range,but whether the spatial gradient of ribbon morphology is fine-tuned in each IHC and how the mitochondrial network is organized to meet local energy demands of synaptic transmission remain unclear.By means of three-dimensional electron microscopy and artificial intelligence-based algorithms,we demonstrated the cell-wide structural quantification of ribbons and mitochondria in mature mid-cochlear IHCs of mice.We found that adjacent IHCs in staggered pairs differ substantially in cell body shape and ribbon morphology gradient as well as mitochondrial organization.Moreover,our analysis argues for a location-specific arrangement of correlated ribbon and mitochondrial function at the basolateral IHC pole.

关键词： Inner hair cell ribbon synapse Mitochondrial network Volume electron microscopy AI-based image processing

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Extrinsic sound stimulations and development of periphery auditory synapses

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Journal of Otology 2015年第2期10卷 47-50页

作者： Kun Hou Shiming Yang Ke Liu Department of OtolaryngologydHead and Neck Surgery General Hospital of PLAPLA Institute of Otolaryngology

The development of auditory synapses is a key process for the maturation of heating function. However, it is still on debate regaralng wnemer the development of auditory synapses is dominated by acquired sound stimulations. In this review, we summarize relevant publications in recent decades to address this issue. Most reported data suggest that extrinsic sound stimulations do affect, but not govern the development of periphery auditory synapses. Overall, periphery auditory synapses develop and mature according to its intrinsic mechanism to build up the synaptic connections between sensory neurons and/or interneurons.

关键词： ribbon synapse Cochlea Periphery Sound stimulation Development

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LOWER DOSE OF AMINOGLYCOSIDE OTOTOXIC EXPOSURE CAUSES PRESYNAPTIC ALTERATIONS ASSOICATED WITH HEARING LOSS

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Journal of Otology 2014年第1期9卷 36-42页

作者： LIU Ke WANG Xiaoyu LI Sijun TANG Siquan XU Yice WANG Xuefeng SUN Jianhe YANG Weiyan YANG Shiming Department of Otolaryngology-Head and Neck Surgery PLA General Hospital PLA Institute of Otolaryngology Department of Otolaryngology-Head and Neck Surgery the Affiliated Hospital North SiChuan Medical College Department of Otolaryngology-Head and Neck Surgery the First Affiliated Hospital Liaoning Medical University

Objective To study presynaptic alternations of cochlear ribbons arising from aminoglycoside ototoxic stimuli in C57BL/6J mice. Methods Animals were injected with low dose gentamicin (100 mg/kg/day) for 14 days, From the 14th to 28th days, the mice were maintained free of gentamicin treatment. Immunohisto-chemistry labeling was employed to trace RIBEYE, a major presynaptic componment of ribbon synapses. RIBEYE/CtBP2 expression levels were assessed and compared with hearing threshold shifts. Auditory func-tion was assessed by auditory brainstem responses. The stereocilia of outer hair cells (OHCs) and IHCs was examined by scanning electron microscopy (SEM). Results Hearing thresholds were elevated with peak hearing loss observed on the 7th day after gentamicin exposure, followed by improvement after the 7th day. RIBEYE/CtBP2 expression directly correlated with observed hearing threshold shifts. Strikingly, we did not see any obvious changes in stereocilia in both OHCs and IHCs until the 28th day. Mild changes in stereocil-ia were only observed in OHCs on the 28th day. Conclusions These findings indicate that presynapse co-chlear ribbons, rather than stereocilia, may be sensitive to aminoglycoside ototoxic exposure in mice cochle-ae. A pattern of RIBEYE/CtBP2 expression changes seems to parallel hearing threshold shifts and suggests presynaptic response properties to lower dosage of aminoglycoside ototoxic stimuli.

关键词： Inner Hair Cells ribbon synapse Aminoglycoside Ototoxicity RIBEYE/CtBP2 Stereocilia

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