Yang Yang, Murtha Kaitlin, Climer Leslie K, Ceriani Federico, Thompson Pierce, Hornak Aubrey J, Marcotti Walter, Simmons Dwayne D
bioRxiv. 2023 Mar 2:2023.03.01.529895. doi: 10.1101/2023.03.01.529895.
Cochlear outer hair cells (OHCs) are responsible for the exquisite frequency selectivity and sensitivity of mammalian hearing. During development, the maturation of OHC afferent connectivity is refined by coordinated spontaneous Ca activity in both sensory and non-sensory cells. Calcium signaling in neonatal OHCs can be modulated by Oncomodulin (OCM, β-parvalbumin), an EF-hand calcium-binding protein. Here, we investigated whether OCM regulates OHC spontaneous Ca activity and afferent connectivity during development. Using a genetically encoded Ca sensor (GCaMP6s) expressed in OHCs in wild-type (Ocm ) and Ocm knockout (Ocm ) littermates, we found increased spontaneous Ca activity and upregulation of purinergic receptors in OHCs from GCaMP6s Ocm cochlea immediately following birth. The afferent synaptic maturation of OHCs was delayed in the absence of OCM, leading to an increased number of ribbon synapses and afferent fibers on GCaMP6s Ocm OHCs before hearing onset. We propose that OCM regulates the spontaneous Ca signaling in the developing cochlea and the maturation of OHC afferent innervation.
耳蜗外毛细胞（OHCs）负责哺乳动物听觉的精确频率选择性和敏感性。在发育过程中，OHC传入连接的成熟通过感觉和非感觉细胞中协调的自发钙活性得到优化。新生OHCs中的钙信号传导可由癌调蛋白（OCM，β-小白蛋白）调节，OCM是一种EF手型钙结合蛋白。在此，我们研究了OCM在发育过程中是否调节OHC自发钙活性和传入连接。利用在野生型（Ocm ）和Ocm基因敲除（Ocm ）同窝幼崽的OHCs中表达的基因编码钙传感器（GCaMP6s），我们发现出生后立即在来自GCaMP6s Ocm 耳蜗的OHCs中自发钙活性增加，嘌呤能受体上调。在没有OCM的情况下，OHCs的传入突触成熟延迟，导致在听力开始前GCaMP6s Ocm OHCs上的带状突触和传入纤维数量增加。我们提出，OCM调节发育中的耳蜗中的自发钙信号传导以及OHC传入神经支配的成熟。
