Maturation of suprathreshold auditory nerve activity involves cochlear CGRP-receptor complex formation.
Maturation of suprathreshold auditory nerve activity involves cochlear CGRP-receptor complex formation.
复制标题
DOI：
10.14814/phy2.12869
复制
发表时间：
2016-07
影响因子：
2.5
通讯作者：
Luebke AE
中科院分区：
文献类型：
--
作者：
Dickerson IM;Bussey-Gaborski R;Holt JC;Jordan PM;Luebke AE
在成年动物中，神经肽降钙素基因相关肽（CGRP）包含在突出到耳蜗的耳蜗传出纤维中，并有助于增加成年听神经中的阈上声诱发活动。同样，CGRP应用于侧线器官（毛细胞器官）增加成年青蛙（变性后30天）的传入神经活动，但这种增加从变性后4-30天开始发育延迟。在这项研究中，我们发现幼年和成年小鼠之间的阈上声诱发活动听觉神经增加也存在发育延迟，与之前在青蛙中观察到的相似。此外，α CGRP基因靶向缺失[CGRP null（−/−）]的幼年小鼠在神经活动方面没有表现出类似的发育增加，这表明CGRP信号传导参与其中。这种发育延迟不是由于CGRP表达的延迟，而是由于受体形成的延迟。我们观察到，声音诱发的神经活动的增加与耳蜗CGRP受体的形成增加相关，这需要三种复合蛋白质（RAMP 1，RCP）才能发挥作用。耳蜗中的CGRP受体形成在1月龄（幼年）时不完全，但在3月龄（成年）时完全，这对应于野生型动物中声音诱发活动的阈上增强的开始。总之，这些数据支持耳蜗功能的模型，增强了成熟的CGRP受体复合物。
In adult animals, the neuropeptide calcitonin gene‐related peptide (CGRP) is contained in cochlear efferent fibers projecting out to the cochlea, and contributes to increased suprathreshold sound‐evoked activity in the adult auditory nerve. Similarly, CGRP applied to the lateral‐line organ (hair cell organ) increases afferent nerve activity in adult frogs (post‐metamorphic day 30), yet this increase is developmentally delayed from post‐metamorphic day 4–30. In this study, we discovered that there was also a developmental delay in increased suprathreshold sound‐evoked activity auditory nerve between juvenile and adult mice similar to what had been observed previously in frog. Moreover, juvenile mice with a targeted deletion of the α CGRP gene [CGRP null (−/−)] did not show a similar developmental increase in nerve activity, suggesting CGRP signaling is involved. This developmental delay is not due to a delay in CGRP expression, but instead is due to a delay in receptor formation. We observed that the increase in sound‐evoked nerve activity is correlated with increased formation of cochlear CGRP receptors, which require three complexed proteins (CLR, RAMP1, RCP) to be functional. CGRP receptor formation in the cochlea was incomplete at 1 month of age (juvenile), but complete by 3 months (adult), which corresponded to the onset of suprathreshold enhancement of sound‐evoked activity in wild‐type animals. Taken together, these data support a model for cochlear function that is enhanced by maturation of CGRP receptor complexes.