Septocingulate and septohippocampal cholinergic pathways: involvement in working/episodic memory

The contribution of the septohippocampal cholinergic pathway to performance of a working/episodic memory task was compared to that of the septocingulate cholinergic path. The septocingulate and septohippocampal cholinergic pathways were selectively destroyed in male Sprague-Dawley rats using site-specific injections of the anti-neuronal immunotoxin 192-IgG saporin into either the hippocampus or the cingulate cortex. 192-IgG-saporin selectively destroys cholinergic neurons and terminals that express the p75 neurotrophin receptor. Following extensive pre-operative training, working memory was assessed using a delayed nonmatch to sample eight arm radial maze task, with delays of 1, 4 and 8 h. The group with lesions of the septohippocampal cholinergic pathway displayed performance deficits on this task which were not related to length of delay. In contrast, the group with lesions of the septocingulate cholinergic pathway did display delay-dependent deficits which were observed at the 4- and 8-h delays, but not at the 1-h delay. These data suggest that the septocingulate cholinergic pathway is critically involved in working/episodic memory but that the septohippocampal cholinergic pathway is either not contributing to working/episodic memory per se or it is involved only at shorter delays.