前额叶皮层边缘下叶-边缘前叶通路及其微环路功能障碍参与慢性炎症痛

慢性痛包含了伤害性感受及情绪、认知等多个维度。前额叶皮层是脑内同时涉及这三个维度的重要核团，从而参与慢性痛时情绪、认知障碍的“共病”。本项目将进一步深入到前额叶内两个重要的亚区，即边缘下叶(IL)和边缘前叶(PL)，拟联合应用清醒大鼠多通道在体电生理记录、光遗传学、在体钙成像等多种技术，在慢性炎症痛模型中深入研究IL-PL通路介导慢性痛的神经通路机制。项目首先明确慢性痛大鼠IL、PL及IL-PL通路电活动特性的变化及其与痛行为、情绪与认知障碍的相关性，进而应用光遗传学技术模拟或挽救IL-PL通路活动变化，证实它们对痛行为影响的因果关系，最后应用在体钙成像和脑片膜片钳技术，明确PL区PV阳性中间神经元在其中的作用。本项目希望证实以下科学假说：慢性炎性痛时，IL功能的减弱，导致PL内抑制性中间神经元功能减弱，继而PL内的锥体神经元脱抑制而兴奋性增高，从而导致慢性炎性痛的发生。

Chronic pain is a common clinical manifestation involving perceptual, affective and cognitive dimensions. The prefrontal cortex (PFC) is a common cortical region for all these processes. With a combinative application of in vivo electrophysiological recording, optogenetics and calcium imaging, the present project aims to examine the role of infralimbic-prelimbic (IL-PL) microcircuit within the PFC in chronic inflammatory pain and associated emotional and cognitive dysfunction. Electrophysiological features of the IL-PL pathway in chronic pain will be first examined, followed by optogenetic manipulations of the pathway. Potential roles of PV-positive interneurons in layer V of the PL will be further examined with in vivo calcium imaging and brain slice patch clamping. The project will test our following hypothesis: in the development of chronic inflammatory pain, hypo-functional pyramidal neurons in the IL induce over-excited downstream PL pyramidal neurons due to disinhibition. This research will deepen our understanding of the role of different PFC subregions in the development of chronic inflammatory pain.