神经肽调控飞蝗行为可塑性的分子机制

Phase transition in the migratory locust is not only an ideal study model for behavioral plasticity, but also the key step for outbreaks of locust plagues. Our previous studies revealed that a series of neuropeptide precursor genes displayed significantly differential expression levels between the central nervous systems of two phases locusts, implicating neuropeptides may play essential roles in the modulation of behavioral plasticity underlying locust phase transition. However, detailed biological significance and regulatory mechanisms remain largely unknown. In this project, we speculate that neuropeptides may participate in the regulation of phase transition by influencing distinct behavioral traits. We will conduct the integrative studies including transcriptomics, phosphorylated proteomics, behavioral studies and gene manipulation to verify this hypothesis. Our study aim to clearly reveal the neuropeptides and corresponding receptors modulating locust behavioral plasticity and illustrate key phosphorylated proteins and genes mediating the biological effects on locust behavioral plasticity controlled by neuropeptides. This work could not only broaden our knowledge on the action model of neuropeptides, but also provide insight into the neural network underlying behavioral plasticity associated with locust phase transition.

飞蝗的两型转变是研究行为可塑性的理想模式，也是蝗灾爆发的重要生物学基础。前期的研究结果表明多种神经肽前体基因在两型飞蝗的神经系统中表现出显著的差异表达，暗示神经肽可能参与飞蝗型变过程中行为可塑性的调控。但其具体功能及调控机制尚不明确。本项目针对神经肽可能通过影响飞蝗特定的行为特征进而参与型变的调控这个科学问题，拟结合转录组学、磷酸化蛋白质组学、行为学和基因操作等技术，明确调控飞蝗行为型变的靶标神经肽及其受体，阐明受靶标神经肽及其受体调控的关键磷酸化蛋白及重要基因， 揭示神经肽调控飞蝗行为可塑性的分子机制。这不仅可以深化对神经肽作用机制的认识，而且有助于深刻理解飞蝗型变中行为可塑性调控的神经网络机制。

飞蝗的行为转变是蝗灾爆发的重要生物学基础。我们的前期研究暗示神经肽可能在飞蝗行为型变过程中发挥重要的调控作用。本项目中，我们发现同源神经肽NPF1a和NPF2通过抑制飞蝗运动活性参与飞蝗行为型变的调控。NPF1a 和NPF2通过作用于各自受体NPFR 和NPYR分别调节一氧化氮合成酶（NOS）的磷酸化水平和转录水平，从而调控飞蝗脑部一氧化氮（NO）的含量。这一工作揭示了NPF/NO信号通路对飞蝗运动可塑性的关键调控作用。通过进一步研究，我们首次揭示了飞蝗中NOS基因的转录调控机制，发现一个保守的转录因子CREB-B通过结合在NOS基因上游的启动子区域直接激活该基因在飞蝗脑部的转录。CREB-B蛋白110位丝氨酸的磷酸化水平显著地响应飞蝗种群密度的变化，并受到神经肽NPF2的负调控。RNA干扰证实CREB-B参与飞蝗运动活性的调控。通过对候选激酶的功能筛选，我们进一步发现蛋白激酶A（PKA）介导了NPF2对CREB-B磷酸化和NOS基因转录的抑制效应。本项目深入揭示了NPF/PKA/CREB-B/NOS这一信号通路对飞蝗行为可塑性的精确调控机制，这一发现将为理解飞蝗型变及蝗灾爆发的分子机制提供重要的理论依据。

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