杀婴与父本行为相互转换的神经内分泌机制研究

Infanticide is a common behavior in mammals. In addition, infanticide and paternal care can mutually transform. Although infanticide has been found in many mammals and its adaptation has been described, its underlying neuroendocrine mechanism remains clear. Because of limitation of animal models, few studies focused on paternal behaviors. Neural circuits that control the transformation between infanticide and paternal care remain unclear. Using mandarin voles with high levels of paternal care and techniques such as behavior, molecular biology, optogenetics, chemical genetics, neurobiology, the present study will reveal association between infanticide, paternal care and levels of oxytocin, vasopressin, serotonin, androgen and their receptors; identify their causal effects on infanticide and paternal care; clarify the neural circuits in which these neuroendocrine chemicals control transformation between infanticide and paternal care. The findings from this study will not only reveal neuroendocrin mechanism underlying transformation between infanticide and paternal care, but also provide information to protection and breeding of wildlife and new targets for prevention and treatment of psychiatry disorder associated with infanticide in human.

杀婴是哺乳动物常见的行为现象，而且存在杀婴与父本行为的相互转化，虽然对杀婴现象和杀婴的适应性方面进行了大量的研究，但是其神经内分泌机制并不清楚。由于动物模型的限制，国内外关于父本行为的研究也较少，而调控杀婴与父本行为转化的神经环路还不清楚。因此，本研究拟利用具有高水平父本行为的棕色田鼠，运用行为学、分子生物学、光遗传学、化学遗传学、钙成像纤维记录等多种研究方法相结合，揭示杀婴行为、父本行为和催产素、加压素、五羟色胺、雄激素等系统之间的关系；明确它们和杀婴、父本行为的因效关系；发现这些神经内分泌物质或神经递质调控杀婴与父本行为相互转变的神经环路。通过该研究不但可揭示杀婴与父本行为相互转换的神经内分泌机制，而且其研究结果可野生动物的保护和繁育提供理论依据，也为人类杀婴相关的精神疾病的预防和治疗提供可能靶点。

亲本照顾对于子代的发育和存活非常重要。未配对的个体面对幼崽往往表现出杀婴或亲本行为，然而，亲本和杀婴的神经环路机制仍不清楚。第一部分：我们发现中缝背核到中视前区5-HT投射调控未配对雄性棕色田鼠的杀婴和父本行为。中缝背核投射到中视前区5-HT主要来自于中缝背核腹侧。在棕色田鼠对幼崽进行理毛时，中缝背核到中视前区5-HT的神经活动显著增加。化学遗传学抑制这条环路降低了杀婴的潜伏期和父本行为；光遗传激活这条环路增强理毛行为和抑制杀婴。第二部分：棕色田鼠在杀婴时下丘脑室旁核的催产素神经元活性较低，而亲本行为发生时下丘脑室旁核的催产素神经元活性较高。腹腔给与催产素可以抑制棕色田鼠的杀婴行为。光遗传激活雌性棕色田鼠下丘脑室旁核催产素神经元显著增加杀婴的潜伏期;对于雄性棕色田鼠，光遗传激活下丘脑室旁核催产素神经元显著增加接近的潜伏期，衔回的潜伏期和父本行为的总时间。光遗传抑制雌雄棕色田鼠下丘脑室旁核催产素神经元显都著降低接近幼崽的潜伏期和杀婴的潜伏期。第三部分：发现在父本行为发生时，下丘脑室旁核到腹侧被盖区或伏隔核的催产素神经元被激活。化学激活/抑制下丘脑室旁核到腹侧被盖区催产素神经环路分别促进/减少了父亲的照顾。化学抑制下丘脑室旁核到腹侧被盖区催产素通路可减少雄性田鼠舔舐和理毛过程中伏隔核多巴胺的释放。光遗传学激活/抑制腹侧被盖区到伏隔核的多巴胺神经环路分别增强/抑制父本行为。此外，化学激活/抑制下丘脑室旁核到伏隔核催产素神经环路的增强/抑制父本行为。通过该研究不但可揭示杀婴与亲本行为的神经环路机制，而且其研究结果可野生动物的保护和繁育提供理论依据，也为人类杀婴相关的精神疾病的预防和治疗提供可能靶点。