Zúñiga Mouret Rodrigo, Greenbaum Jordyn P, Doll Hannah M, Brody Eliza M, Iacobucci Emma L, Roland Nicholas C, Simamora Roy C, Ruiz Ivan, Seymour Rory, Ludwick Leanne, Krawitz Jacob A, Groneberg Antonia H, Marques João C, Laborde Alexandre, Rajan Gokul, Del Bene Filippo, Orger Michael B, Jain Roshan A
Department of Biology, Haverford College, Haverford, PA 19041, USA.
Department of Biology, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA.
iScience. 2024 Mar 8;27(4):109455. doi: 10.1016/j.isci.2024.109455. eCollection 2024 Apr 19.
Animals constantly integrate sensory information with prior experience to select behavioral responses appropriate to the current situation. Genetic factors supporting this behavioral flexibility are often disrupted in neuropsychiatric conditions, such as the autism-linked gene which supports acoustically evoked habituation learning. encodes an AP2 endocytosis adaptor complex subunit, although its behavioral mechanisms and importance have been unclear. Here, we show that multiple AP2 subunits regulate acoustically evoked behavior selection and habituation learning in zebrafish. Furthermore, biases escape behavior choice in sensory modality-specific manners, and broadly regulates action selection across sensory contexts. We demonstrate that the AP2 complex functions acutely in the nervous system to modulate acoustically evoked habituation, suggesting several spatially and/or temporally distinct mechanisms through which AP2 regulates escape behavior selection and performance. Altogether, we show the AP2 complex coordinates action selection across diverse contexts, providing a vertebrate model for 's role in human conditions including autism spectrum disorder.
动物不断地将感官信息与先前的经验相结合，以选择适合当前情况的行为反应。支持这种行为灵活性的遗传因素在神经精神疾病中常常受到破坏，例如与自闭症相关的基因，它支持听觉诱发的习惯化学习。该基因编码一种AP2内吞衔接复合体亚基，但其行为机制和重要性尚不清楚。在这里，我们表明多个AP2亚基调节斑马鱼的听觉诱发行为选择和习惯化学习。此外，它以特定于感觉模态的方式偏向逃避行为选择，并广泛调节跨感觉背景的动作选择。我们证明AP2复合体在神经系统中急性发挥作用，以调节听觉诱发的习惯化，这表明AP2调节逃避行为选择和表现的几种空间和/或时间上不同的机制。总之，我们表明AP2复合体在不同背景下协调动作选择，为其在包括自闭症谱系障碍在内的人类疾病中的作用提供了一个脊椎动物模型。
