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Abstract：
Habituation is an adaptive learning process that enables animals to adjust innate behaviors to changes in their environment. Despite its well-documented implications for a wide diversity of behaviors, the molecular and cellular basis of habituation learning is not well understood. Using whole-genome sequencing of zebrafish mutants isolated in an unbiased genetic screen, we identified the palmitoyltransferase Huntingtin interacting protein 14 (Hip14) as a critical regulator of habituation learning. We demonstrate that Hip14 regulates depression of sensory inputs onto an identified hindbrain neuron and provide evidence that Hip14 palmitoylates the Shaker-like K+ voltage-gated channel subunit (Kv1.1), thereby regulating Kv1.1 subcellular localization. Furthermore, we show that, like for Hip14, loss of Kv1.1 leads to habituation deficits and that Hip14 is dispensable in development and instead acts acutely to promote habituation. Combined, these results uncover a previously unappreciated role for acute posttranslational palmitoylation at defined circuit components to regulate learning.
摘要：
习惯是一种适应性学习过程，使动物能够根据环境的变化调整先天行为。尽管它对广泛多样的行为有充分的记载，习惯性学习的分子和细胞基础还没有得到很好的理解。使用在无偏遗传筛选中分离的斑马鱼突变体的全基因组测序，我们确定棕榈酰转移酶亨廷顿蛋白相互作用蛋白14(Hip14)是习惯性学习的关键调节因子.我们证明了Hip14调节对已识别的后脑神经元的感觉输入的抑制，并提供了Hip14棕榈酰化Shaker样K电压门控通道亚基（Kv1.1）的证据。从而调节Kv1.1亚细胞定位。此外，我们证明，与Hip14一样，Kv1.1的丢失会导致习惯性缺陷，而Hip14在发展中可有可无，反而会敏锐地促进习惯性。合并,这些结果揭示了先前未被重视的急性翻译后棕榈酰化在确定的电路组件中调节学习的作用。
