Chronic cerebral hypoperfusion (CCH) is considered a preclinical condition of mild cognitive impairment and thought to precede dementia. However, as the principal cholinergic source of hippocampus, whether the septo-hippocampal neurocircuit was impaired after CCH is still unknown. In this study, we established the CCH rat model by bilateral common carotid artery occlusion (2VO). Under anesthesia, the medial septum (MS) of rats was stimulated to evoke the field excitatory post-synaptic potential (fEPSP) in the pyramidal cell layer of dCA1. Consequently, we observed decreased amplitude of fEPSP and increased paired-pulse ratio (PPR) after 8-week CCH. After tail pinch, we also found decreased peak frequency and shortened duration of hippocampal theta rhythm in 2VO rats, indicating the dysfunction of septo-hippocampal neurocircuit. Besides, by intracerebroventricularly injecting GABAergic inhibitor (bicuculline) and cholinergic inhibitors (scopolamine and mecamylamine), we found that CCH impaired both the pre-synaptic cholinergic release and the post-synaptic nAChR function in MS–dCA1 circuits. These results gave an insight into the role of CCH in the impairment of cholinergic MS–dCA1 neurocircuits. These findings may provide a new idea about the CCH-induced neurodegenerative changes.

慢性脑灌注不足（CCH）被认为是轻度认知障碍的临床前病状，被认为早于痴呆。然而，作为海马的主要胆碱能来源，尚不清楚在CCH后隔海马神经回路是否受损。在这项研究中，我们通过双侧颈总动脉闭塞（2VO）建立了CCH大鼠模型。在麻醉下，刺激大鼠的中隔（MS）引起dCA1锥体细胞层中的田间兴奋性突触后电位（fEPSP）。因此，我们观察到在8周的CCH后fEPSP的幅度降低，而配对脉冲比（PPR）却增加了。尾巴捏捏后，我们还发现2VO大鼠的峰值频率降低，海马theta节律持续时间缩短，表明中隔海马神经回路功能异常。除了，通过脑室内注射GABA能抑制剂（比库洛林）和胆碱能抑制剂（东pol碱和美加明），我们发现CCH损害了MS–dCA1回路中突触前胆碱能释放和突触后nAChR功能。这些结果使我们深入了解了CCH在胆碱能MS–dCA1神经回路损害中的作用。这些发现可能提供有关CCH诱导的神经退行性变化的新想法。