Brain-Derived Neurotrophic Factor Is Involved in Activity-Dependent Tonotopic Refinement of MNTB Neurons.
Brain-Derived Neurotrophic Factor Is Involved in Activity-Dependent Tonotopic Refinement of MNTB Neurons.
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DOI：
10.3389/fncir.2022.784396
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发表时间：
2022
影响因子：
3.5
通讯作者：
Kim JH
中科院分区：
文献类型：
--
作者：
Wollet M;Kim JH
在哺乳动物脑中，听觉脑干核团根据声频反应性进行拓扑排列。在出生后发育过程中，主要神经元的轴突起始段（AIS）根据在斜方体内侧核（MNTB）内沿着音调轴的位置进行结构细化。然而，听觉脑干中AIS沿着音调轴的结构细化的分子机制尚未被探索。我们测试的假设，脑源性神经营养因子（BDNF）是一个分子介导的MNTB的结构发展的活动依赖性的方式。使用BDNF杂合突变（BDNF+/-）小鼠，我们通过评估AIS结构和相关的内在神经元特性，研究了整体BDNF减少对MNTB神经元结构和功能发育的影响。BDNF减少抑制MNTB中主要神经元沿着tonotopic轴的结构和功能分化。在发育的关键时期，增强的声音输入已被证明可以增强MNTB神经元AIS的结构细化。然而，在BDNF +/-小鼠中，MNTB神经元在重复的声音刺激后没有显示出AIS的这种活性依赖性结构修饰。此外，BDNF+/-小鼠在暴露于16 kHz声音后缺乏确定的神经元活动的等幅带，表明tonotopy退化。总之，听觉脑干神经元的结构发育和功能完善需要生理水平的BDNF来建立适当的音调梯度。
In the mammalian brain, auditory brainstem nuclei are arranged topographically according to acoustic frequency responsiveness. During postnatal development, the axon initial segment (AIS) of principal neurons undergoes structural refinement depending on location along the tonotopic axis within the medial nucleus of the trapezoid body (MNTB). However, the molecular mechanisms underlying the structural refinement of the AIS along the tonotopic axis in the auditory brainstem have not been explored. We tested the hypothesis that brain-derived neurotrophic factor (BDNF) is a molecular mediator of the structural development of the MNTB in an activity-dependent manner. Using BDNF heterozygous mutant (BDNF+/–) mice, we examined the impact of global BDNF reduction on structural and functional development of MNTB neurons by assessing AIS structure and associated intrinsic neuronal properties. BDNF reduction inhibits the structural and functional differentiation of principal neurons along the tonotopic axis in the MNTB. Augmented sound input during the critical period of development has been shown to enhance the structural refinement of the AIS of MNTB neurons. However, in BDNF +/– mice, MNTB neurons did not show this activity-dependent structural modification of the AIS following repeated sound stimulation. In addition, BDNF+/– mice lacked a defined isofrequency band of neuronal activity following exposure to 16 kHz sound, suggesting degradation of tonotopy. Taken together, structural development and functional refinement of auditory brainstem neurons require physiological levels of BDNF to establish proper tonotopic gradients.
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