The medial septum (MS) is an important modulator of hippocampal function. The degree of damage in which the particular set of septo-hippocampal projections contributes to the deficits of spatial memory with concomitant changes of hippocampal receptors expression has not been studied till present. Therefore, we investigated spatial memory and the expression level of cholinergic (α7 nACh and M1), GABAergic (α1 subunit of GABAA) and glutamatergic (NR2B subunit of NMDA and GluR 1 subunit of AMPA) receptors in the hippocampus following selective lesions of cholinergic and GABAergic septo-hippocampal projection. Learning process and long-term spatial memory were assessed using a Morris water maze. The obtained results revealed that in contrast to cholinergic lesions, rats with MS GABAergic lesions exhibit a retention deficit in 3 days after training. Western blot analyses revealed the MS cholinergic lesions have significant effect on the expression level of the M1 mACh receptors, while MS GABAergic lesions induce dramatic modulations of hippocampal glutamatergic, cholinergic and GABAergic receptors expression. These results for the first time demonstrated that selective lesions of MS cholinergic and GABAergic neurons differentially affect long-term spatial memory and the memory deficit after MS GABAergic lesion is paralleled with significant changes of hippocampal glutamate, GABA and acetylcholine receptors expression.

内侧隔膜（MS）是海马功能的重要调节器。迄今为止，尚未研究特定组的间隔海马投射导致空间记忆缺陷以及海马受体表达的伴随变化的损伤程度。因此，我们研究了胆碱能和 M1 选择性损伤后海马的空间记忆和胆碱能（α7 nACh 和 M1）、GABA 能（GABAA 的 α1 亚基）和谷氨酸能（NMDA 的 NR2B 亚基和 AMPA 的 GluR 1 亚基）受体的表达水平。GABA能间隔海马投射。使用莫里斯水迷宫评估学习过程和长期空间记忆。获得的结果显示，与胆碱能损伤相比，MS GABA能损伤的大鼠在训练后3天内表现出保留缺陷。蛋白质印迹分析显示，MS 胆碱能损伤对 M1 mACh 受体的表达水平有显着影响，而 MS GABA 能损伤可诱导海马谷氨酸、胆碱能和 GABA 能受体表达的显着调节。这些结果首次证明，MS胆碱能和GABA能神经元的选择性损伤对长期空间记忆有不同的影响，并且MS GABA能损伤后的记忆缺陷与海马谷氨酸、GABA和乙酰胆碱受体表达的显着变化是平行的。