A REEXAMINATION OF THE ROLE OF BASAL FOREBRAIN CHOLINERGIC NEURONS INSPATIAL WORKING-MEMORY

The basal forebrain cholinergic system, which innervates widespread co rtical and limbic structures; has traditionally been considered import ant for learning and memory. The use of an immunotoxin, 192 IgG-sapori n, has brought this functional designation into question; selective im munolesions of basal forebrain cholinergic neurons have failed to repr oduce a number of behavioral deficits that were observed with less sel ective lesion methods. Recent reports, however, have indicated that a mild impairment is observed in rats on a spatial working memory task a fter 192 IgG-saporin lesions of the rostral groups of cholinergic neur ons located in the medial septal area (MSA). Those studies used a lesi on protocol in which a single large volume injection of the immunotoxi n was made into the MSA. In the current study, multiple small injectio ns were made at the locations of cholinergic neurons in the MSA, produ cing a cholinergic depletion comparable to that reported in the earlie r studies where deficits were observed. In the current study, however, rats with cholinergic lesions had no impairment in the spatial workin g 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 p roduce a deficit in spatial working memory. (C) 1998 Elsevier Science Ltd. All rights reserved.