海马突触可塑性损伤是学习认知能力下降的病理生理基础。申请人团队前期证实高龄孕鼠子代学习认知能力下降，存在神经营养因子缺乏，但导致突触可塑性损伤的具体分子机制尚不清楚。初级纤毛是细胞重要的信号传感器，其介导的LKB1/AMPK通路有能量传感作用。前期研究发现高龄孕鼠子代海马细胞初级纤毛发生或功能障碍，同时有自噬缺陷。由此推测高龄妊娠子代未成熟脑在能量缺乏环境下，海马神经元初级纤毛介导的LKB1/AMPK信号通路不能正常活化，导致自噬缺陷，影响突触结构与功能，导致突触可塑性损伤。本研究拟从初级纤毛着手，围绕自噬，从结构到功能，结合体内与体外实验，研究初级纤毛-自噬-突触可塑性的科学联系，并针对性地干预初级纤毛与LKB1/AMPK信号途径，观察能否改善高龄妊娠子代海马突触可塑性损伤。为研究高龄妊娠子代突触可塑性损伤的病理机制提供理论依据，为采取防治措施改善高龄妊娠子代学习认知能力提供新的途径。

Hippocampal synaptic plasticity damage is the pathophysiological basis for learning cognitive impairment. The applicant's team previously confirmed that the learning and cognitive abilities of the offspring of the advanced maternal age (AMA) are reduced, and there is a lack of neurotrophic factors, but the specific molecular mechanism leading to synaptic plastic damage is still unclear. Primary cilia is an important sensory organelle of cells, and the LKB1 / AMPK pathway mediated by it is also energy sensor. Previous studies have found the dysfunction of primary ciliogenesis and autophagy deficiency in offspring of AMA. It is speculated that the LKB1/AMPK signaling pathway mediated by the primary cilia of hippocampal neurons cannot be normally activated in the immature brain of AMA offspring, resulting in autophagy deficiency, affecting synaptic structure and function, and causing synaptic plastic damage .This study starts from primary cilia, and focuses on autophagy. It is from structure to function, combing experiments in vivo and that in vitro, to explore the scientific relationship among primary cilia, autophagy and synaptic plasticity, and try some interventional changes in primary cilia and AMPK pathway to improve the hippocampal synaptic plasticity in the offspring. It provides a basis for studying the pathological mechanism of synaptic plasticity damage in the offspring of AMA, and provides a new way to improve cognitive ability of the offspring.