Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; University of Basel, 4003 Basel, Switzerland.
Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
Cell Rep. 2017 Jan 3;18(1):185-197. doi: 10.1016/j.celrep.2016.12.021.
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.
音调拓扑是听觉通路的一个标志，为声音辨别提供了基础。目前对于转录因子在脑干耳蜗神经元中协调突触前输入的音高精确性方面的作用知之甚少。我们发现，在前腹侧耳蜗核的 Atoh1 衍生的谷氨酸能布什细胞中，缺失 Hoxa2 和 Hoxb2 功能后，宽输入拓扑和声音传递在很大程度上得以保留。然而，在纯音刺激下，Hox2 突变体中耳蜗神经元激活的同频带的精细突触细化和锐化受损，导致行为测试中声音频率辨别能力缺陷。这些结果确立了 Hox 因子在连接的音高细化以及确保哺乳动物听觉回路中声音传递精度方面的作用。
