中缝背核至岛叶的5-羟色胺能投射通路参与痛觉及负性情绪调控的机制

Although the dorsal raphe nucleus (DR) and insular cortex (IC) are important areas for the modulation of pain and negative emotion, our knowledge for their functional connection is rather poor. In our pilot works, we found that 5-HTergic neurons in the DR send projections to the IC. By exploring optogenetic techniques to activate the 5-HTergic DR-IC projecting fibers, it's shown that the excitatory synaptic transmission in IC is either potentiated or depressed. Similarly, activation of 5-HT induced hyper- or hyposensitive behavioral responses in pain and fear test. In the present study, we want to introduce the serotonin transporter (Sert)-cre mice to specifically test the regulatory effect of 5-HTergic DR-IC projection to IC neuronal activity, as well as the chronic pain and related negative emotion changes in behavioral mice, by integrating neurobiological techniques. Our proposed study will be important for revealing the regulatory mechanism of 5-HT in cortex and valuable for clinical treatment for chronic pain and related negative emotion.

中缝背核(DR)和岛叶(IC)均是疼痛与负性情绪调控的重要脑区。然而，二者之间功能联系的研究却十分匮乏。我们前期的研究工作表明，DR内的5-HT能神经元向IC发出投射。通过光遗传学技术特异性地激活DR至IC的5-HT能投射纤维，可以对IC内的兴奋性突触传递以及动物的痛阈值和负性情绪起到兴奋或抑制的双向调控作用。本项目拟以5-HT转运体（Sert)-cre小鼠为实验对象，通过综合应用神经科学的先进方法，研究DR发出的5-HT能投射纤维对IC内神经元活性的调节效应和机制，探讨该通路对慢性痛及负性情绪发生发展的影响。该研究将为5-HT在皮层的作用机制提供重要的实验依据，也有益于临床慢性痛及痛相关负性情绪的治疗和药物研发。

中缝背核(DR)和岛叶(IC)均是疼痛调控的重要脑区。然而，二者之间功能联系的研究却十分匮乏。5-HT在IC内的作用机制也很不清楚。在本项目中，我们主要通过使用Med64多通道进行记录，研究5-HT对IC内多个记录位点的总体效应，最终明确了5-HT低浓度兴奋，高浓度抑制IC内局部兴奋性的整体量效关系。5-HT低浓度的效应主要是通过5-HT2A受体介导，而高浓度抑制效应是通过5-HT1A受体介导。进一步的行为学以及核团成像结果表明低浓度的5-HT主要起到促痛效应而高浓度5-HT主要起到镇痛效应。本项目综合利用了形态学，行为药理学，电生理学，光遗传学，脑成像等技术，探讨了DR发出的5-HT能投射纤维对IC内神经元活性的调节效应和受体机制。该研究将为5-HT在皮层的作用机制提供重要的实验依据，也有益于临床慢性痛的治疗和药物研发。在该项目的资助下，发表SCI论文3篇，接收1篇，发表核心期刊2篇。培养博士生4名，硕士生1名。