Sensory Neuron Diversity in the Inner Ear Is Shaped by Activity.

Sensory Neuron Diversity in the Inner Ear Is Shaped by Activity.
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DOI:
10.1016/j.cell.2018.07.007
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发表时间:
2018-08-23
期刊:
影响因子:
64.5
通讯作者:
Goodrich LV
Goodrich LV
中科院分区:
生物学1区
文献类型:
--
作者:
Shrestha BR;Chia C;Wu L;Kujawa SG;Liberman MC;Goodrich LV

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在听觉系统中,I型螺旋神经节神经元(sgn)将复杂的声学信息从内毛细胞(IHCs)传递到脑干。尽管sgn在生理和解剖特性上存在差异,但尚不清楚哪些特征是内源性的,哪些反映了突触伙伴的输入。利用单细胞RNA测序,我们将小鼠I型sgn分子分类为三种亚型,它们表达Ca2+结合蛋白、离子通道调节剂、引导分子和转录因子的独特组合。基于连通性和对年龄相关损失的易感性,这些亚型与生理上定义的亚型相对应。亚型之间和跨张力轴的其他内在差异突出了sgn在听觉加工中意想不到的积极作用。SGN身份在出生后出现,并在缺乏ihc驱动活动的耳聋小鼠模型中被破坏。这些结果阐明了SGN多样性的范围、性质和起源,对先天性耳聋的治疗具有指导意义。小鼠l型螺旋神经节神经元的单细胞分析表征了三种功能不同的亚型,揭示了听觉加工的见解,对治疗先天性耳聋具有重要意义。通过单细胞rna测序,Shrestha和他的同事们定义了内耳神经元的三种亚型,它们在不同亚型和局部上具有不同的生理相关分子表达。SGN多样化始于出生后,需要ihc驱动的活动,与年龄相关和先天性耳聋有关。
In the auditory system, Type I spiral ganglion neurons (SGNs) convey complex acoustic information from inner hair cells (IHCs) to the brainstem. Although SGNs exhibit variation in physiological and anatomical properties, it is unclear which features are endogenous and which reflect input from synaptic partners. Using single-cell RNA sequencing, we derived a molecular classification of mouse Type I SGNs into three subtypes that express unique combinations of Ca2+ binding proteins, ion channel regulators, guidance molecules, and transcription factors. Based on connectivity and susceptibility to age-related loss, these subtypes correspond to those defined physiologically. Additional intrinsic differences among subtypes and across the tonotopic axis highlight an unexpectedly active role for SGNs in auditory processing. SGN identities emerge postnatally and are disrupted in a mouse model of deafness that lacks IHC-driven activity. These results elucidate the range, nature, and origins of SGN diversity, with implications for treatment of congenital deafness. Single cell analyses of mouse Type l spiral ganglion neurons characterize three functionally distinct subtype, reveling insights into auditory processing with implication for treating congenital deafness. Using single cell RNA-sequencing, Shrestha and colleagues define three subtypes of inner ear neurons with differential expression of physiologically relevant molecules across subtypes and tonotopically. SGN diversification begins postnatally and requires IHC-driven activity, with implications for age-related and congenital deafness.
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