Abstract：
Ribbon synapses in the cochlear hair cells are subject to extensive pruning and maturation processes before hearing onset. Previous studies have highlighted the pivotal role of thyroid hormone (TH) in this developmental process, yet the detailed mechanisms are largely unknown. In this study, we found that the thyroid hormone receptor α (Thrα) is expressed in both sensory epithelium and spiral ganglion neurons in mice. Hypothyroidism, induced by Pax8 gene knockout, significantly delays the synaptic pruning during postnatal development in mice. Detailed spatiotemporal analysis of ribbon synapse distribution reveals that synaptic maturation involves not only ribbon pruning but also their migration, both of which are notably delayed in the cochlea of Pax8 knockout mice. Intriguingly, postnatal hyperthyroidism, induced by intraperitoneal injections of liothyronine sodium (T3), accelerates the pruning of ribbon synapses to the mature state without affecting the auditory functions. Our findings suggest that thyroid hormone does not play a deterministic role but rather controls the timing of cochlear ribbon synapse maturation.
摘要：
耳蜗毛细胞中的带状突触在听力开始之前经历广泛的修剪和成熟过程。先前的研究强调了甲状腺激素（TH）在这一发育过程中的关键作用，然而，详细的机制在很大程度上是未知的。在这项研究中,我们发现甲状腺激素受体α（Thrα）在小鼠的感觉上皮和螺旋神经节神经元中都有表达。甲状腺功能减退,Pax8基因敲除诱导，显著延迟小鼠出生后发育过程中的突触修剪。带状突触分布的详细时空分析表明，突触成熟不仅涉及带状修剪，还涉及其迁移，两者在Pax8基因敲除小鼠的耳蜗中都明显延迟。有趣的是，出生后甲状腺功能亢进，通过腹腔注射利塞罗宁钠（T3）诱导，加速带状突触的修剪到成熟状态，而不影响听觉功能。我们的发现表明，甲状腺激素并不发挥决定性作用，而是控制耳蜗带状突触成熟的时机。
