Chinese Institutes for Medical Research (CIMR) and Department of Neurobiology, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 10069, China.
PKU-IDG/McGovern Institute for Brain Research, Peking-Tsinghua Center for Life Sciences, School of Life Sciences, School of Pharmaceutical Sciences, School of Chemistry and Chemical Engineering, Peking University, Beijing 100871, China; Chinese Institute for Brain Research, Beijing, Zhongguangcun Life Science Park, Beijing, China.
Neuron. 2023 May 3;111(9):1468-1485.e7. doi: 10.1016/j.neuron.2023.02.010. Epub 2023 Mar 2.
Maternal affiliation by infants is the first social behavior of mammalian animals. We report here that elimination of the Tph2 gene essential for serotonin synthesis in the brain reduced affiliation in mice, rats, and monkeys. Calcium imaging and c-fos immunostaining showed maternal odors activation of serotonergic neurons in the raphe nuclei (RNs) and oxytocinergic neurons in the paraventricular nucleus (PVN). Genetic elimination of oxytocin (OXT) or its receptor reduced maternal preference. OXT rescued maternal preference in mouse and monkey infants lacking serotonin. Tph2 elimination from RN serotonergic neurons innervating PVN reduced maternal preference. Reduced maternal preference after inhibiting serotonergic neurons was rescued by oxytocinergic neuronal activation. Our genetic studies reveal a role for serotonin in affiliation conserved from mice and rats to monkeys, while electrophysiological, pharmacological, chemogenetic, and optogenetic studies uncover OXT downstream of serotonin. We suggest serotonin as the master regulator upstream of neuropeptides in mammalian social behaviors.
婴儿的母婴依恋是哺乳动物的第一社会行为。我们在这里报告，消除大脑中 5-羟色胺合成所必需的 Tph2 基因会减少小鼠、大鼠和猴子的母婴依恋。钙成像和 c-fos 免疫染色显示，母体气味会激活中缝核（RN）中的 5-羟色胺能神经元和室旁核（PVN）中的催产素能神经元。催产素（OXT）或其受体的基因缺失会降低母婴偏好。OXT 可挽救缺乏 5-羟色胺的小鼠和猴婴儿的母婴偏好。从投射到 PVN 的 RN 5-羟色胺能神经元中消除 Tph2 会降低母婴偏好。抑制 5-羟色胺能神经元后，催产素能神经元的激活可挽救母婴偏好降低。我们的遗传研究表明，5-羟色胺在从小鼠和大鼠到猴子的母婴依恋中发挥作用，而电生理学、药理学、化学遗传学和光遗传学研究揭示了 5-羟色胺下游的催产素。我们认为 5-羟色胺是哺乳动物社会行为中神经肽的主调控因子。
