Hox2 Genes Are Required for Tonotopic Map Precision and Sound Discrimination in the Mouse Auditory Brainstem
Hox2 Genes Are Required for Tonotopic Map Precision and Sound Discrimination in the Mouse Auditory Brainstem
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DOI：
10.1016/j.celrep.2016.12.021
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发表时间：
2017-01-03
期刊：
影响因子：
8.8
通讯作者：
Rijli, Filippo M.
中科院分区：
文献类型：
--
作者：
Karmakar, Kajari;Narita, Yuichi;Rijli, Filippo M.
声调复制是听觉通路的一个标志，为声音辨别提供了基础。关于转录因子在脑干耳蜗神经元中参与协调突触前输入的音调精确度的问题，人们知之甚少。我们发现，在前腹侧耳蜗核Atoh1来源的谷氨酸能丛状细胞缺乏Hoxa2和Hoxb2功能的情况下，广泛的输入地形图和声音传递基本保持不变。然而，在Hox2突变体中，纯音刺激下耳蜗神经元激活的细微突触细化和等频带锐化受到损害，导致行为测试中的声频辨别能力缺陷。这些结果确立了HOX因子在连接的纯音精炼和确保哺乳动物听觉回路中声音传递的精确度方面的作用。
Tonotopy is a hallmark of auditory pathways and provides the basis for sound discrimination. Little is known about the involvement of transcription factors in brainstem cochlear neurons orchestrating the tonotopic precision of pre-synaptic input. We found that in the absence of Hoxa2 and Hoxb2 function in Atoh1-derived glutamatergic bushy cells of the anterior ventral cochlear nucleus, broad input topography and sound transmission were largely preserved. However, fine-scale synaptic refinement and sharpening of isofrequency bands of cochlear neuron activation upon pure tone stimulation were impaired in Hox2 mutants, resulting in defective sound-frequency discrimination in behavioral tests. These results establish a role for Hox factors in tonotopic refinement of connectivity and in ensuring the precision of sound transmission in the mammalian auditory circuit.