Cloning primers.

Sensory thresholds enable animals to regulate their behavioral responses to environmental threats. Despite the importance of sensory thresholds for animal behavior and human health, we do not yet have a full appreciation of the underlying molecular-genetic and circuit mechanisms. The larval zebrafish acoustic startle response provides a powerful system to identify molecular mechanisms underlying establishment of sensory thresholds and plasticity of thresholds through mechanisms like habituation. Using this system, we identify Cadherin-16 as a previously undescribed regulator of sensory gating. We demonstrate that Cadherin-16 regulates sensory thresholds via an endocrine organ, the corpuscle of Stannius (CS), which is essential in zebrafish for regulating Ca2+ homeostasis. We further show that Cadherin-16 regulates whole-body calcium and ultimately behavior through the hormone Stanniocalcin 1l (Stc1l), and the IGF-regulatory metalloprotease, Papp-aa. Finally, we demonstrate the importance of the CS through ablation experiments that reveal its role in promoting normal acoustic sensory gating. Together, our results uncover a previously undescribed brain non-autonomous pathway for the regulation of behavior and underscore Ca2+ homeostasis as a critical process underlying sensory gating in vivo.

感觉阈值（sensory thresholds）可帮助动物调控其针对环境威胁的行为应答。尽管感觉阈值对动物行为与人类健康均至关重要，但目前我们仍未完全阐明其背后的分子遗传与神经环路机制。斑马鱼幼体听觉惊吓反应（acoustic startle response）是一个强大的研究模型，可用于鉴定感觉阈值建立以及习惯化等阈值可塑性机制背后的分子调控通路。依托该模型，我们鉴定出钙粘蛋白16（Cadherin-16）为一种此前未被报道的感觉门控（sensory gating）调控因子。我们证实，钙粘蛋白16通过内分泌器官斯坦尼乌斯小体（corpuscle of Stannius, CS）调控感觉阈值——该结构在斑马鱼体内对钙稳态（Ca²⁺ homeostasis）的维持具有不可或缺的作用。我们进一步发现，钙粘蛋白16通过激素斯钙素1l（Stanniocalcin 1l, Stc1l）以及胰岛素样生长因子（IGF）调控型金属蛋白酶Papp-aa，调控斑马鱼全身钙水平并最终影响行为。最后，我们通过消融实验证实了斯坦尼乌斯小体的重要性，揭示其在维持正常听觉感觉门控中的关键作用。综上，本研究揭示了一条此前未被报道的、调控行为的脑非自主性通路，并明确了钙稳态是体内感觉门控的关键调控过程。