Abstract
This experiment was based on the establishment of an analogue of post-traumatic stress disorder (PTSD) in mice, aiming to explore the regulatory effects of the medial septum (MS) and the hippocampus (HIP) on spatial memory impairment in mice, and to establish a theoretical foundation for revealing the pathological basis of PTSD-related spatial memory impairment. The PTSD mouse model was prepared, behavioral testing, FluoroGold (FG) retrograde tracing technique, viral tracing technique, in vivo fiber photometry recording technique, chemogenetic technology and in vivo electrophysiological recording techniques were applied to observe and analyze the changes in spatial memory ability and the central regulatory mechanism. PTSD mice showed heightened anxiety, impaired spatial memory, suppressed Sch-CA1 long-term potentiation, and hyperactivity of MS-CA1 cholinergic neurons; chemogenetic inhibition of this pathway rescued both the behavioral and synaptic plasticity deficits. The regulation of spatial memory impairment in PTSD mice involves MS-resident cholinergic neurons. We found a cholinergic pathway connection between MS and CA1, and this pathway may regulate murine spatial cognition by influencing the synaptic plasticity of Sch-CA1.