Lesions of the medial septum which produce deficits in working/spatial memory do not impair long-term potentiation in the CA3 region of the rat hippocampus in vivo.

The effects of removing the septohippocampal pathway on the ability to induce long-term potentiation (LTP) in the CA3 region of the hippocampus was examined in vivo in rats. The septal input to the hippocampus was destroyed by electrolytic lesioning of the medial septum (MS). Prior to electrophysiological investigation, working/spatial memory of lesioned and control rats was tested using an 8-arm radial maze task. Maze performance was significantly impaired in animals with MS lesions. LTP inducibility was examined in the commissural fimbrial fibre- and mossy fibre (mf)-CA3 pathways in MS-lesioned and control rats. The pre-tetanus values in MS-lesioned rats tended to be smaller than those in controls, in both pathways. High-frequency stimulation of the commissural fibres resulted in a sustained increase in the orthodromic population spike and EPSP amplitude in both control and MS-lesioned rats. The magnitude of potentiation was similar in both groups. In control rats, high-frequency stimulation of the mf potentiated the amplitude of both the population spike and EPSP; in MS-lesioned rats, the EPSP amplitude alone was significantly increased by mf high-frequency stimulation. Hippocampal acetylcholinesterase (AChE) content was severely reduced bilaterally in MS-lesioned rats with working/spatial memory impairments, indicating that the lesions were effective in destroying the cholinergic septohippocampal input. These findings suggest that, in contrast to working/spatial memory processes, LTP at CA3 synapses is not dependent upon the integrity of the septohippocampal pathway.