褐家鼠气味对小家鼠繁殖行为的影响及其机制

The brown rat (Rattus norvegicus) and the house mouse (Mus musculus) are commensal pests; and the two species sometimes may share the same habitats. The mouse-killing behavior (muricidc) in rat is instinct, which may be critical in their interpsecific interactions. The interactions should be the primary determinant regulating their distribution and population dynamics. Our proposals are aimed at exploring the underlying mechanisms of rat odor-induced reproductive suppression in mice. Both laboratory and field experiments will be performed through an interdisciplinary approach including analytical chemistry, behavior, neuroendocrine, molecular techniques and immunohistochemistry. Our researches will focus on the chronic effects of rat odor exposure in mice. To be specific, (1) the effects of rat urine odor on mice in various aspects of reproductive behavior such as male-male competition, female mate choice, sexual behavior, pregnancy, materal care and offspring fitness; (2) the volatile profiles and the key components of the rat urine which indicating the predation risk, and the ingredients to mimic rat odor cues consisting of the synthetic compounds; (3) the respective importances of and interactions between innate responses and learned olfactory responses to rat odor, using mice with rat experience (somatosensory and gustatory experience) as subjects and rat-naive mice as control; (4) the covariation and possible interactions among HPA axis, HPG axis, neurotransmiters and olfaction-mediated fearful response; (5) the effect of social condition (e.g.,paired-caging and anti-fearful responses ; alarm odor and social transmission of fear ) on the rat odor-induced fearful and stressful responses; (6) in nature, how the rat urine and key volatiles blend to affect the reproductive success and population dynamic of feral mice. In conclusion, our findings will answer the questions of how and why the physiology and reproductive deficiencies occur following chronic exposure of rat urine odor; and the key components of rat urine will be identify, which may signal predation-like risk and regulate the population of feral mice in the field. Four to 6 high influential papers are expected to be published, and 3-5 postgraduate students will be trained.

褐家鼠（Rattus norvegicus）和小家鼠（Mus musculus）是两种常见的害鼠。由于褐家鼠具有嗜杀小家鼠的本能行为（muricide），褐家鼠对小家鼠的影响是其种间关系的重要内容。本项目以褐家鼠气味对小家鼠繁殖的抑制现象和内在机制为核心，以室内研究为主，结合野外实验，利用化学、行为、分子、神经、种群生态等学科的方法，阐明(1)褐家鼠尿液气味长期刺激对小家鼠性选择、性行为、怀孕率、母性行为及后代适合度等的影响；(2)褐家鼠尿液气味中编码该种间信息的关键化学组成；(3)本能（innate）和习得(learned)的嗅觉识别在小家鼠恐惧反应中的作用及激活的的神经通路；(4)HPA轴、HPG轴和单胺类递质与小家鼠嗅觉应激的相互影响；(5)社群条件对小家鼠应激反应的影响；（6）褐家鼠气味对小家鼠种群变化的影响。发表有影响的SCI论文4-6篇；培养研究生3-5名。

褐家鼠（Rattus norvegicus）和小家鼠（Mus musculus）是两种常见的两种家栖害鼠。由于褐家鼠具有嗜杀小家鼠的本能行为（muricide），褐家鼠常常被看作小家鼠的天敌。我们以褐家鼠气味对小家鼠的抑制现象和机制为核心，以室内研究为主，利用化学、行为、分子、神经等学科的方法，研究发现：.第一，发现大鼠气味其主要成分都为4-庚酮，2-庚酮，9-羟基-2壬酮，4-甲基苯酚， 4-乙基苯酚等。这些成分可能是褐家鼠气味影响小家鼠行为和生理的关键成分。大鼠气味明显引起雌性小鼠的不孕现象，C57B/6各17对，对照组在8周内共有8只母鼠生育14窝，51只子鼠；实验组共3只母鼠生育4窝，11只子鼠。说明大鼠气味明显引起了小鼠的流产或怀孕成功。然而，单纯对雄性小鼠的影响却有些不同，C57小鼠在大鼠屋饲养两个月后尿液的气味反而对雌性的吸引力增加。.第二，利用Tph2（大脑5-HT合成酶）基因敲除的小鼠， 我们证明：大脑五羟色胺(5-HT)和其它分子的相互作用可能调节了小鼠对褐家鼠气味的反应。长期天敌暴露会降低Tph2+/+雄鼠的斗争性和尿液气味性吸引力，前额叶皮质中AR，ERα和GluR4及海马中TrkBTc和5-HTR1A的表达均下降；但是这些抑制效应在Tph2-/-雄鼠中则消失了。第三，利用近交品系小鼠（C57BL/6）证明，雄鼠之间的攻击行为强弱存在个体分化，雄雄长期互作导致社会优势和从属等级的分化，来自包皮腺的三种挥发性雄性信息素含量升高。同时，优势雄鼠的后代仍然表现出较强的攻击行为，仍然可以出现优势雄鼠的信息素。说明可能表观遗传和社会互作决定了社会优势信息素的表达。第四，利用C57B/6和BALB/c两个近交品系的小鼠， 进行交叉饲养发现，母性效应影响了雄性小鼠的信息素组成，使其它雄鼠对其亲属关系的嗅觉识别产生误差。.第五，首次证明小家鼠（小鼠）尿液主蛋白（major urine protein, MUP）中的雄性信息素MUP20（darcin）与社会等级有关,并受到肝脏中促肾上腺皮质激素释放激素受体2(CRHR2) 的抑制性调节。 也就是说社会应激可以通过生理内分泌应激反应调节性信息素的产生，从而影响繁殖成功。.6篇 SCI文章标注发表， 1位博士生和2位硕士生毕业，2位博士后出站。