Differential effects of selective immunotoxic lesions of medial septal cholinergic cells on spatial working and reference memory.

The effect of injection into the medial septum of a toxin selective for cholinergic neurons, 192 IgG-saporin, was examined in rats trained to perform 2 versions of the radial 8-arm maze task. Rats were first trained to perform a task with varying delays (0, 1, 2 min) imposed between the 4th correct arm choice and access to all 8 arms. Lesioned rats made significantly more errors in the first 4 choices compared with controls and significantly more errors after delays; however, this effect was not delay dependent. Rats were then trained on a different version of this 8-arm maze task in which they learned to avoid 2 arms that were never baited. There was no treatment effect on acquisition of this task. These data are consistent with the hypothesis that the cholinergic projection to the hippocampus facilitates the acquisition of information into the system responsible for short-term memory for locations visited (spatial working memory) but is not involved in retention of this information. It also appears to play no role in either the acquisition or retention of place-nonreward associations (spatial reference memory).