帕金森病（PD）是最常见的运动障碍疾病。除运动症状外，认知记忆障碍等非运动症状（NMS）对患者的功能影响更为明显，因此成为治疗的新目标。但由于病因及机制不明，对症的药物治疗对认知障碍缺乏有效性，且副作用大。大量流行病学研究表明运动在延缓疾病进展，减轻NMS方面发挥作用。而5-HT3受体（5-HT3Rs）是运动诱导海马可塑性和神经发生的必要条件。我们以往的工作也证实了5-HT3Rs在认知记忆中的重要作用。但5-HT3Rs在运动改善PD认知记忆损害中的作用机制有待阐明。本课题将运用行为学、电生理、神经示踪和光遗传学等方法在PD小鼠模型上明确了该作用，并研究其在神经发生，突触可塑性，神经环路等方面的机制。首次探讨DA与5-HT3Rs相互作用的新机制。研究结果将有助于理解5-HT/DA系统crosstalk在运动改善PD认知障碍中的作用，并可能为PD认知功能障碍的治疗提供新的信息和方法。

Parkinson’s disease (PD) is the most common neurodegenerative disorder that mainly affects the motor system. In addition to its cardinal motor symptoms, a number of non-motor symptoms (NMS) such as cognitive dysfunction are also associated with PD, which has a more significant impact on patients’ quality-of-life. So its treatment is becoming a new target for therapy. However, as the cause of PD is not clear, current drug therapy based on symptomatic relief not only has side effects, but also lacks effectiveness in the treatment of cognitive dysfunction. Data from epidemiological studies has been accumulating to suggest that exercise may have a role to play in alleviating NMS of PD. 5-HT3 receptor is essential for exercise-induced hippocampal plasticity and neurogenesis. Our previous works also confirmed the important role of 5-HT3Rs in cognition and memory. However, the effect and mechanisms of 5-HT3Rs in exercise-ameliotrating PD cognitive impairment remains to be elucidated. In this study, using behavioral, electrophysiological, neuro-trace and optogenetics methods, we will determine this effect and study the mechanisms of neurogenesis, synaptic plasticity and neural circuits. A novel mechanism for the interaction of DA with the 5-HT3 receptor will also be explored. The results of the study will help to understand the role of 5-HT/DA crosstalk in exercise ameliorating cognitive impairment and may provide useful insights into the treatment of cognitive dysfunction in PD.