听神经病及亚型听突触病:声音编码与突触研究进展
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摘要
听神经病及亚型听突触病是目前耳科学领域国际研究的难点和热点。随着听神经病在遗传学、生理学、分子细胞学以及动物模型的深入研究,逐渐明确并定义听突触病是听神经病中的一个亚型,进一步认识到突触在听神经的神经传导和声音编码中的重要作用,对听神经病及亚型听突触病的发病机制有了更加清晰的认识。本文总结国内外听神经病及亚型听突触病的最新研究进展,综述目前与其相关密切的毛细胞声音编码和突触功能研究进展的部分内容,便于更好的理解听神经病及其亚型听突触病,为临床精准的分子分型诊断干预提供理论依据。
Auditory neuropathy and subtype auditory synaptopathy are the difficulties and hot spots in international research in the field of otology. With the in-depth study of genetics, physiology, molecular cytology and animal models of auditory neuropathy, it has gradually become clarified and defined that auditory synaptopathy is a subtype of auditory neuropathy. The critical role of synapses in the nerve conduction and sound coding of the auditory nerve has been further recognized, and clearer understanding of the pathogenesis of auditory neuropathy and subtype auditory synaptopathy has been achieved. This paper summarized the up-to-date research progress on auditory neuropathy and subtype auditory synaptopathy nationally and internationally, as well as some of the recent research progress on sound coding and synaptic function of hair cell which is closely related to it, so as to achieve better understanding of auditory neuropathy and subtype auditory synaptopathy, and to provide theoretica.
Auditory neuropathy and subtype auditory synaptopathy are the difficulties and hot spots in international research in the field of otology. With the in-depth study of genetics, physiology, molecular cytology and animal models of auditory neuropathy, it has gradually become clarified and defined that auditory synaptopathy is a subtype of auditory neuropathy. The critical role of synapses in the nerve conduction and sound coding of the auditory nerve has been further recognized, and clearer understanding of the pathogenesis of auditory neuropathy and subtype auditory synaptopathy has been achieved. This paper summarized the up-to-date research progress on auditory neuropathy and subtype auditory synaptopathy nationally and internationally, as well as some of the recent research progress on sound coding and synaptic function of hair cell which is closely related to it, so as to achieve better understanding of auditory neuropathy and subtype auditory synaptopathy, and to provide theoretica.
引文
1 Moser T,Starr A.Auditory neuropathy--neural and synaptic mechanisms[J].Nat Rev Neurol,2016,12(3):135-149.
2 Deborah Hayes,Yvonne S.Sininger,Jerry Northern,et al.Guidelines for Identification and Management of Infants and Young Children with Auditory Neuropathy Spectrum Disorder.Co-Chairs,2008.
3王秋菊,Starr A.听神经病:从发现到渐入精准[J].中华耳鼻咽喉头颈外科杂志,2018,53(3):161-171.Wang QJ,Starr A.Auditory neuropathy:from discovery to gradual precision[J].Chin J Otorhinolaryngol Head Neck Surg,2018,53(3):161-171.
4顾瑞,于黎明.中枢性低频感音神经性听力减退[J].中华耳鼻咽喉科杂志,1992,27(1):27-29.Gu R,Yu LM.Central low frequency sensorineural hearing loss[J].Chinese Journal of Otorhinolaryngology Head and Neck Surgery,1992,27(1):27-29.
5 Starr A,Picton TW,Sininger Y,et al.Auditory neuropathy[J].Brain,1996,119(Pt3):741-753.
6 Moser T,Vogl C.New insights into cochlear sound encoding[J].F1000Res,2016,5(1-9).
7 Fuchs PA.Time and intensity coding at the hair cell's ribbon synapse[J].J Physiol,2005,566(Pt 1):7-12.
8 Moser T,Neef A,Khimich D.Mechanisms underlying the temporal precision of sound coding at the inner hair cell ribbon synapse[J].J Physiol,2006,576(Pt 1):55-62.
9 Rutherford MA,Chapochnikov NM,Moser T.Spike encoding of neurotransmitter release timing by spiral ganglion neurons of the cochlea[J].J Neurosci,2012,32(14):4773-4789.
10 Nouvian R,Beutner D,Moser T,et al.Structure and function of the hair cell ribbon synapse[J].J Membr Biol,2006,209(2-3):153-165.
11陈丽平,商秀丽.内毛细胞带状突触结构及功能的研究进展[J].医学综述,2011,17(19):2899-2902.Chen LP,Shang XL.Advances in research on the ribbon synapse structure and function of inner hair cells[J].Medical Recapitulate,2011,17(19):2899-2902.
12 Schmitz F,K?nigstorfer A,Südhof TC.RIBEYE,a component of synaptic ribbons:A protein's journey through evolution provides insight into synaptic ribbon function[J].Neuron,2000,28(3):857-872.
13 Schmitz F.The Making of Synaptic Ribbons:How They Are Built and What They Do[J].Neuroscientist,2009,15(6):611-624.
14 Buran BN,Strenzke N,Neef A,et al.Onset coding is degraded in auditory nerve fibers from mutant mice lacking synaptic ribbons[J].J Neurosci,2010,30(22):7587-7597.
15 Frank T,Rutherford MA,Strenzke N,et al.Bassoon and the synaptic ribbon organize Ca2+channels and vesicles to add release sites and promote refilling[J].Neuron,2010,68(4):724-738.
16 Khimich D,Nouvian R,Pujol R,et al.Hair cell synaptic ribbons are essential for synchronous auditory signalling[J].Nature,2005,434(7035):889-894.
17 Seal RP,Akil O,Yi E,et al.Sensorineural deafness and seizures in mice lacking vesicular glutamate transporter 3[J].Neuron,2008,57(2):263-275.
18 Ruel J,Emery S,Nouvian R,et al.Impairment of SLC17A8 encoding vesicular glutamate transporter-3,VGLUT3,underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice[J].Am J Hum Genet,2008,83(2):278-292.
19 Platzer J,Engel J,Schrott-Fischer A,et al.Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+channels[J].Cell,2000,102(1):89-97.
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22 Glowatzki E,Fuchs PA..Transmitter release at the hair cell ribbon synapse[J].Nat Neurosci,2002,5(2):147-154.
23 Chapochnikov NM,Takago H,Huang CH,et al.Uniquantal release through a dynamic fusion pore is a candidate mechanism of hair cell exocytosis[J].Neuron,2014,83(6):1389-13403.
24 Lacas-Gervais S,Guo J,Strenzke N,et al.BetaIVSigma1 spectrin stabilizes the nodes of Ranvier and axon initial segments[J].J Cell Biol,2004,166(7):983-990.
25 Hossain WA,Antic SD,Yang Y,et al.Where is the spike generator of the cochlear nerve?Voltage-gated sodium channels in the mouse cochlea[J].J Neurosci,2005,25(29):6857-6868.
26 Jung S,Maritzen T,Wichmann C,et al.Disruption of adaptor protein 2μ(AP-2μ)in cochlear hair cells impairs vesicle reloading of synaptic release sites and hearing[J].EMBO J,2015,34(21):2686-2702.
27 Pangrsic T,Lasarow L,Reuter K,et al.Hearing requires otoferlin-dependent efficient replenishment of synaptic vesicles in hair cells[J].Nat Neurosci,2010,13(7):869-876.
28 Parkinson NJ,Olsson CL,Hallows JL,et al.Mutant beta-spectrin4 causes auditory and motor neuropathies in quivering mice[J].Nat Genet,2001,29(1):61-65.
29 Matthews G,Fuchs P.The diverse roles of ribbon synapses in sensory neurotransmission[J].Nat Rev Neurosci,2010,11(12):812-822.
30 Moser T,Brandt A,Lysakowski A.Hair cell ribbon synapses[J].Cell Tissue Res,2006,326(2):347-359.
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32 Bucurenciu I,Kulik A,Schwaller B,et al.Nanodomain coupling between Ca2+channels and sensors of exocytosis at fast mammalian synapses[J].Nature Reviews Neuroscience,2012,13(1):7-21.
33 Matveev V,Bertram R,Sherman A.Calcium cooperativity of exocytosis as a measure of Ca2+channel domain overlap[J].Brain Research,2011,1398(none):126-138.
34 Stanley EF.The Nanophysiology of Fast Transmitter Release[J].Trends Neurosci,2016,39(3):183-197.
35 Roberts WM,Jacobs RA,Hudspeth AJ.Colocalization of ion channels involved in frequency selectivity and synaptic transmission at presynaptic active zones of hair cells[J].Journal of Neuroscience,1990,10(11):3664-3684.
36 Wong AB,Rutherford MA,Gabrielaitis M,et al.Developmental refinement of hair cell synapses tightens the coupling of Ca2+influx to exocytosis[J].Embo Journal,2014,33(3):247-264.
37 Brandt A,Khimich D,Moser T.Few CaV1.3 channels regulate the exocytosis of a synaptic vesicle at the hair cell ribbon synapse[J].J Neurosci,2005,25(50):11577-11585.
38 Zampini V,Johnson SL,Franz C,et al.Burst activity and ultrafast activation kinetics of CaV1.3 Ca2+channels support presynaptic activity in adult gerbil hair cell ribbon synapses[J].J Physiol,2013,591(16):3811-3820.
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40 Meyer AC,Frank T,Khimich D,et al.Tuning of synapse number,structure and function in the cochlea[J].Nat Neurosci,2009,12(4):444-453.
41 Wong AB,Jing Z,Rutherford MA,et al.Concurrent maturation of inner hair cell synaptic Ca2+in?ux and auditory nerve spontaneous activity around hearing onset in mice[J].J Neurosci,2013,33(26):10661-10666.
42 Wynne DP,Zeng FG,Bhatt S,et al.Loudness adaptation accompanying ribbon synapse and auditory nerve disorders[J].Brain,2013,136(Pt 5):1626-1638.
43 Varga R,Avenarius MR,Kelley PM,et al.OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele[J].JMed Genet,2006,43(7):576-581.
44 Marlin S,Feldmann D,Nguyen Y,et al.Temperature-sensitive auditory neuropathy associated with an otoferlin mutation:deafening fever![J].Biochem Biophys Res Commun,2010,394(3):737-742.
45 Wang DY,Wang YC,Weil D,et al.Screening mutations of OTOFgene in Chinese patients with auditory neuropathy,including a familial case of temperature-sensitive auditory neuropathy[J].BMC Med Genet,2010,11(79).
46 Romanos J,Kimura L,Fávero ML,et al.Novel OTOF mutations in Brazilian patients with auditory neuropathy[J].J Hum Genet,2009,54(7):382-385.
47 Matsunaga T,Mutai H,Kunishima S,et al.A prevalent founder mutation and genotype-phenotype correlations of OTOF in Japanese patients with auditory neuropathy[J].Clin Genet,2012,82(5):425-432.
48 Schwander M,Sczaniecka A,Grillet N,et al.A forward genetics screen in mice identifies recessive deafness traits and reveals that pejvakin is essential for outer hair cell function[J].J Neurosci,2007,27(9):2163-75.
49王大勇,王秋菊,兰兰,等.76例听神经病患者OTOF基因突变分析[J].听力学及言语疾病杂志,2007,15(6):432-437.Wang DY,Wang QJ,Lan L,et al.Analysis of OTOF gene mutation in 76 patients with auditory neuropathy[J].Journal of Audiology and Speech Pathology,2007,15(6):432-437.
50 Zhang QJ,Han B,Lan L,et al.High frequency of OTOF mutations in Chinese infants with congenital auditory neuropathy spectrum disorder[J].Clin Genet,2016,90(3):238-246.
51 Zhang Q,Lan L,Shi W,et al.Temperature sensitive auditory neuropathy[J].Hearing Research,2016,335(53-63).
52齐悦.听神经病谱系障碍患者临床特征及SLC17A8基因型与表型的临床意义研究[J].中国人民解放军医学院,2013.Qi Y.Clinical characteristics of patients with auditory neuropathy spectrum disorder and clinical significance of SLC17A8 genotype and phenotype[J].Chinese People's Liberation Army Medical College,2013.
53 Petek E,Windpassinger C,Mach M,et al.Molecular characterization of a 12q22-q24 deletion associated with congenital deafness:confirmation and refinement of the DFNA25 locus[J].Am J Med Genet A,2003,117A(2):122-126.
54 Olichon A,Landes T,Arnauné-Pelloquin L,et al.Effects of OPA1 mutations on mitochondrial morphology and apoptosis:relevance to ADOA pathogenesis[J].J Cell Physiol,2007,211(2):423-430.
55 FerréM,Bonneau D,Milea D,et al.Molecular screening of 980cases of suspected hereditary optic neuropathy with a report on77 novel OPA1 mutations[J].Hum Mutat,2009,30(7):E692-705.
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2 Deborah Hayes,Yvonne S.Sininger,Jerry Northern,et al.Guidelines for Identification and Management of Infants and Young Children with Auditory Neuropathy Spectrum Disorder.Co-Chairs,2008.
3王秋菊,Starr A.听神经病:从发现到渐入精准[J].中华耳鼻咽喉头颈外科杂志,2018,53(3):161-171.Wang QJ,Starr A.Auditory neuropathy:from discovery to gradual precision[J].Chin J Otorhinolaryngol Head Neck Surg,2018,53(3):161-171.
4顾瑞,于黎明.中枢性低频感音神经性听力减退[J].中华耳鼻咽喉科杂志,1992,27(1):27-29.Gu R,Yu LM.Central low frequency sensorineural hearing loss[J].Chinese Journal of Otorhinolaryngology Head and Neck Surgery,1992,27(1):27-29.
5 Starr A,Picton TW,Sininger Y,et al.Auditory neuropathy[J].Brain,1996,119(Pt3):741-753.
6 Moser T,Vogl C.New insights into cochlear sound encoding[J].F1000Res,2016,5(1-9).
7 Fuchs PA.Time and intensity coding at the hair cell's ribbon synapse[J].J Physiol,2005,566(Pt 1):7-12.
8 Moser T,Neef A,Khimich D.Mechanisms underlying the temporal precision of sound coding at the inner hair cell ribbon synapse[J].J Physiol,2006,576(Pt 1):55-62.
9 Rutherford MA,Chapochnikov NM,Moser T.Spike encoding of neurotransmitter release timing by spiral ganglion neurons of the cochlea[J].J Neurosci,2012,32(14):4773-4789.
10 Nouvian R,Beutner D,Moser T,et al.Structure and function of the hair cell ribbon synapse[J].J Membr Biol,2006,209(2-3):153-165.
11陈丽平,商秀丽.内毛细胞带状突触结构及功能的研究进展[J].医学综述,2011,17(19):2899-2902.Chen LP,Shang XL.Advances in research on the ribbon synapse structure and function of inner hair cells[J].Medical Recapitulate,2011,17(19):2899-2902.
12 Schmitz F,K?nigstorfer A,Südhof TC.RIBEYE,a component of synaptic ribbons:A protein's journey through evolution provides insight into synaptic ribbon function[J].Neuron,2000,28(3):857-872.
13 Schmitz F.The Making of Synaptic Ribbons:How They Are Built and What They Do[J].Neuroscientist,2009,15(6):611-624.
14 Buran BN,Strenzke N,Neef A,et al.Onset coding is degraded in auditory nerve fibers from mutant mice lacking synaptic ribbons[J].J Neurosci,2010,30(22):7587-7597.
15 Frank T,Rutherford MA,Strenzke N,et al.Bassoon and the synaptic ribbon organize Ca2+channels and vesicles to add release sites and promote refilling[J].Neuron,2010,68(4):724-738.
16 Khimich D,Nouvian R,Pujol R,et al.Hair cell synaptic ribbons are essential for synchronous auditory signalling[J].Nature,2005,434(7035):889-894.
17 Seal RP,Akil O,Yi E,et al.Sensorineural deafness and seizures in mice lacking vesicular glutamate transporter 3[J].Neuron,2008,57(2):263-275.
18 Ruel J,Emery S,Nouvian R,et al.Impairment of SLC17A8 encoding vesicular glutamate transporter-3,VGLUT3,underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice[J].Am J Hum Genet,2008,83(2):278-292.
19 Platzer J,Engel J,Schrott-Fischer A,et al.Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+channels[J].Cell,2000,102(1):89-97.
20 Brandt A,Striessnig J,Moser T.CaV1.3 channels are essential for development and presynaptic activity of cochlear inner hair cells[J].J Neurosci,2003,23(34):10832-10840.
21 Mo ZL,Adamson CL,Davis RL..Dendrotoxin-sensitive K(+)currents contribute to accommodation in murine spiral ganglion neurons[J].J Physiol,2002,542(Pt 3):763-778.
22 Glowatzki E,Fuchs PA..Transmitter release at the hair cell ribbon synapse[J].Nat Neurosci,2002,5(2):147-154.
23 Chapochnikov NM,Takago H,Huang CH,et al.Uniquantal release through a dynamic fusion pore is a candidate mechanism of hair cell exocytosis[J].Neuron,2014,83(6):1389-13403.
24 Lacas-Gervais S,Guo J,Strenzke N,et al.BetaIVSigma1 spectrin stabilizes the nodes of Ranvier and axon initial segments[J].J Cell Biol,2004,166(7):983-990.
25 Hossain WA,Antic SD,Yang Y,et al.Where is the spike generator of the cochlear nerve?Voltage-gated sodium channels in the mouse cochlea[J].J Neurosci,2005,25(29):6857-6868.
26 Jung S,Maritzen T,Wichmann C,et al.Disruption of adaptor protein 2μ(AP-2μ)in cochlear hair cells impairs vesicle reloading of synaptic release sites and hearing[J].EMBO J,2015,34(21):2686-2702.
27 Pangrsic T,Lasarow L,Reuter K,et al.Hearing requires otoferlin-dependent efficient replenishment of synaptic vesicles in hair cells[J].Nat Neurosci,2010,13(7):869-876.
28 Parkinson NJ,Olsson CL,Hallows JL,et al.Mutant beta-spectrin4 causes auditory and motor neuropathies in quivering mice[J].Nat Genet,2001,29(1):61-65.
29 Matthews G,Fuchs P.The diverse roles of ribbon synapses in sensory neurotransmission[J].Nat Rev Neurosci,2010,11(12):812-822.
30 Moser T,Brandt A,Lysakowski A.Hair cell ribbon synapses[J].Cell Tissue Res,2006,326(2):347-359.
31 Wichmann C,Moser T.Relating structure and function of inner hair cell ribbon synapses[J].Cell Tissue Res,2015,361(1):95-114.
32 Bucurenciu I,Kulik A,Schwaller B,et al.Nanodomain coupling between Ca2+channels and sensors of exocytosis at fast mammalian synapses[J].Nature Reviews Neuroscience,2012,13(1):7-21.
33 Matveev V,Bertram R,Sherman A.Calcium cooperativity of exocytosis as a measure of Ca2+channel domain overlap[J].Brain Research,2011,1398(none):126-138.
34 Stanley EF.The Nanophysiology of Fast Transmitter Release[J].Trends Neurosci,2016,39(3):183-197.
35 Roberts WM,Jacobs RA,Hudspeth AJ.Colocalization of ion channels involved in frequency selectivity and synaptic transmission at presynaptic active zones of hair cells[J].Journal of Neuroscience,1990,10(11):3664-3684.
36 Wong AB,Rutherford MA,Gabrielaitis M,et al.Developmental refinement of hair cell synapses tightens the coupling of Ca2+influx to exocytosis[J].Embo Journal,2014,33(3):247-264.
37 Brandt A,Khimich D,Moser T.Few CaV1.3 channels regulate the exocytosis of a synaptic vesicle at the hair cell ribbon synapse[J].J Neurosci,2005,25(50):11577-11585.
38 Zampini V,Johnson SL,Franz C,et al.Burst activity and ultrafast activation kinetics of CaV1.3 Ca2+channels support presynaptic activity in adult gerbil hair cell ribbon synapses[J].J Physiol,2013,591(16):3811-3820.
39 Frank T,Khimich D,Neef A,et al.Mechanisms contributing to synaptic Ca2+signals and their heterogeneity in hair cells[J].PNatl Acad Sci USA,2009,106(11):4483-4488.
40 Meyer AC,Frank T,Khimich D,et al.Tuning of synapse number,structure and function in the cochlea[J].Nat Neurosci,2009,12(4):444-453.
41 Wong AB,Jing Z,Rutherford MA,et al.Concurrent maturation of inner hair cell synaptic Ca2+in?ux and auditory nerve spontaneous activity around hearing onset in mice[J].J Neurosci,2013,33(26):10661-10666.
42 Wynne DP,Zeng FG,Bhatt S,et al.Loudness adaptation accompanying ribbon synapse and auditory nerve disorders[J].Brain,2013,136(Pt 5):1626-1638.
43 Varga R,Avenarius MR,Kelley PM,et al.OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele[J].JMed Genet,2006,43(7):576-581.
44 Marlin S,Feldmann D,Nguyen Y,et al.Temperature-sensitive auditory neuropathy associated with an otoferlin mutation:deafening fever![J].Biochem Biophys Res Commun,2010,394(3):737-742.
45 Wang DY,Wang YC,Weil D,et al.Screening mutations of OTOFgene in Chinese patients with auditory neuropathy,including a familial case of temperature-sensitive auditory neuropathy[J].BMC Med Genet,2010,11(79).
46 Romanos J,Kimura L,Fávero ML,et al.Novel OTOF mutations in Brazilian patients with auditory neuropathy[J].J Hum Genet,2009,54(7):382-385.
47 Matsunaga T,Mutai H,Kunishima S,et al.A prevalent founder mutation and genotype-phenotype correlations of OTOF in Japanese patients with auditory neuropathy[J].Clin Genet,2012,82(5):425-432.
48 Schwander M,Sczaniecka A,Grillet N,et al.A forward genetics screen in mice identifies recessive deafness traits and reveals that pejvakin is essential for outer hair cell function[J].J Neurosci,2007,27(9):2163-75.
49王大勇,王秋菊,兰兰,等.76例听神经病患者OTOF基因突变分析[J].听力学及言语疾病杂志,2007,15(6):432-437.Wang DY,Wang QJ,Lan L,et al.Analysis of OTOF gene mutation in 76 patients with auditory neuropathy[J].Journal of Audiology and Speech Pathology,2007,15(6):432-437.
50 Zhang QJ,Han B,Lan L,et al.High frequency of OTOF mutations in Chinese infants with congenital auditory neuropathy spectrum disorder[J].Clin Genet,2016,90(3):238-246.
51 Zhang Q,Lan L,Shi W,et al.Temperature sensitive auditory neuropathy[J].Hearing Research,2016,335(53-63).
52齐悦.听神经病谱系障碍患者临床特征及SLC17A8基因型与表型的临床意义研究[J].中国人民解放军医学院,2013.Qi Y.Clinical characteristics of patients with auditory neuropathy spectrum disorder and clinical significance of SLC17A8 genotype and phenotype[J].Chinese People's Liberation Army Medical College,2013.
53 Petek E,Windpassinger C,Mach M,et al.Molecular characterization of a 12q22-q24 deletion associated with congenital deafness:confirmation and refinement of the DFNA25 locus[J].Am J Med Genet A,2003,117A(2):122-126.
54 Olichon A,Landes T,Arnauné-Pelloquin L,et al.Effects of OPA1 mutations on mitochondrial morphology and apoptosis:relevance to ADOA pathogenesis[J].J Cell Physiol,2007,211(2):423-430.
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