内侧前额叶皮层缺血损伤对其网络振荡的影响及机制研究

The medial prefrontal cortex (mPFC) plays an important role in executing of higher brain functions, for example, learning and memory. cerebral ischemia-related cognitive functional lesions were thought to be associated with structure damage and dysfunction of mPFC. However, the underlying mechanisms remain unknown. Recently, some studies demonstrated that neural network oscillations within mPFC or hippocampal-mPFC mediate the key mechanisms in different stages of learning and memory, including acquisition, consolidation and retrial. The widely distributed hyperpolarization-activated cyclic nucleotide gated (HCN) channels are essential for neural oscillation and information integration. What is more important, successful performance in learning and memory depends on the excitatory background neural inputs from the arousal-promoting system. In this project, we will firstly investigate the effects of local mPFC ischemia on neural oscillations within mPFC and hippocampal-mPFC in different stages of learning and memory by advanced techniques, such as in-vivo multi-channel recording. Then, we attempt to explore the mechanisms of mPFC ischemia -induced dysfunction of neural network oscillations by focusing on structure and function of HCN channels, and background excitatory inputs from the arousal-promoting systems by using optogenetics, microdialysis and patch clamp techniques. We expect to provide new insights for development of strategies to clinically improve the cerebral ischemia -related cognitive functional.

内侧前额叶皮层（mPFC）在学习记忆等高级认知功能中具有重要作用。脑缺血损伤所致认知损害与mPFC结构和功能受损密切相关，但其机制并不清楚。近年研究表明，mPFC内部神经元群和海马-mPFC神经元群网络振荡是其认知功能最为关键机制。同时，广泛分布超极化激活环核苷酸门控（HCN）离子通道对神经元网络振荡、输入信息整合具有极为重要作用。认知过程依赖于觉醒系统对mPFC输入所提供的背景兴奋水平。基于此，本项目拟选择mPFC为研究对象，采用在体电生理、光遗传学、微透析、膜片钳等技术，研究mPFC缺血后mPFC内部网络振荡以及海马-mPFC网络振荡在认知过程不同阶段改变特征，并从HCN通道结构、功能，以及觉醒系统兴奋性输入两个方面探讨其发生机制。以期为临床寻找干预脑缺血所致认知功能损害方法提供新的思路与实验依据。

内侧前额叶皮层（mPFC）在学习记忆等高级认知功能中具有重要作用。脑缺血损伤所致认知损害与mPFC结构和功能受损密切相关，但其机制并不清楚。我们从分子、细胞及微环路的水平上，研究了缺血引起内侧前额叶网络振荡功能活动的变化，并解析缺血后不同神经元兴奋性变化的离子通道机制。在此基础上，我们利用在体光遗传技术，从神经元环路水平上解析了前额叶内侧皮层对于学习记忆的作用与功能。该结果对于我们理解前额叶调控时间性联合运动学习等神经环路机制 ，以及前额叶内侧皮层缺血相关认知、行为功能损伤防治提供了新思路。