A re-examination of the role of basal forebrain cholinergic neurons in spatial working memory

The basal forebrain cholinergic system, which innervates widespread cortical and limbic structures, has traditionally been considered important for learning and memory. The use of an immunotoxin, 192 IgG-saporin, has brought this functional designation into question; selective immunolesions of basal forebrain cholinergic neurons have failed to reproduce a number of behavioral deficits that were observed with less selective lesion methods. Recent reports, however, have indicated that a mild impairment is observed in rats on a spatial working memory task after 192 IgG-saporin lesions of the rostral groups of cholinergic neurons located in the medial septal area (MSA). Those studies used a lesion protocol in which a single large volume injection of the immunotoxin was made into the MSA. In the current study, multiple small injections were made at the locations of cholinergic neurons in the MSA, producing a cholinergic depletion comparable to that reported in the earlier studies where deficits were observed. In the current study, however, rats with cholinergic lesions had no impairment in the spatial working memory task, even when delays ranging from 60 s to 8 h were imposed within a trial. The current report indicates that selective removal of cholinergic neurons in the basal forebrain may not be sufficient to produce a deficit in spatial working memory.