海马-内侧前额叶皮质通路在脓毒症脑病认知功能障碍中的作用及其机制研究

认知功能障碍是脓毒症脑病（SAE）最常见的临床表现之一，也是导致脓毒症患者生活质量下降的重要因素，其发病机制远未阐明。大量研究显示，海马-内侧前额叶皮质（HPC-mPFC）通路在学习记忆中具有关键作用。我们在前期研究中发现，通过特异性激活HPC-mPFC通路，能显著改善SAE大鼠的认知行为学，据此，我们提出假说：HPC-mPFC通路在SAE认知功能障碍中具有重要作用。本项目将采用光遗传学/化学遗传学、神经示踪、电生理等技术，明确HPC-mPFC通路在SAE认知功能障碍中的作用，并深入探索该通路涉及的神经、电生理和分子机制。通过以上研究，最终揭示HPC-mPFC通路在SAE认知功能障碍中的作用机制，为其发病机制和治疗提供理论基础。

Cognitive dysfunction is one of the most common clinical manifestations of sepsis-associated encephalopathy (SAE), which is also an important reason for the poor quality of life in septic patients. However, the mechanisms of SAE related cognitive dysfunction are far from clear. Many previous studies have proved the critical role of hippocampal- medial prefrontal (HPC-mPFC) pathway in learning and memory. In our preliminary study, we have found that specifically activating the HPC-mPFC projection neurons improved the cognitive behavior of SAE rats. Therefore, we hypothesize that the HPC-mPFC pathway plays an important role in SAE related cognitive dysfunction. In this study, we will employ optogenetics/ chemogennetics, neural tracer technique, electrophysiology and other techniques to clarify the role of HPC-mPFC pathway in SAE related cognitive dysfunction, and further explore the neural, electrophysiological and molecular mechanisms involved in this pathway. Based on this study, we will reveal the role of hippocampal-medial prefrontal pathway in sepsis associated encephalopathy and its mechanisms, which will shed light on its pathology mechanisms and its treatment.