THE ROLE OF THE CENTRAL CHOLINERGIC PROJECTIONS IN COGNITION - IMPLICATIONS OF THE EFFECTS OF SCOPOLAMINE ON DISCRIMINATION-LEARNING BY MONKEYS

In humans, administration of the cholinergic antagonist scopolamine im pairs the encoding of information into long-term memory and has effect s on other cognitive processes. It has been supposed that it is inhibi tion of the rising cholinergic projections from the basal forebrain, s pecifically from the basal nucleus of Meynert (NBM) to the neocortex a nd from the medial septum/vertical limb of the diagonal band of Broca (MS/VDB) to the hippocampus, that results in these cognitive impairmen ts. In this paper, we describe the effects of scopolamine treatment in monkeys on learning different sorts of visual discrimination and visu ospatial conditional tasks and compare these results to the effects of lesions of the rising cholinergic projections. Experiments in rodents in which these projections have been selectively destroyed have faile d to produce a consensus view of the functions of these two areas. In particular, highly specific immunotoxic lesions of the NBM have largel y failed to produce changes in task performance that can be interprete d as resulting from a cognitive impairment. In monkeys, lesions of the NBM produce modest or short-lasting, impairments in visual discrimina tion learning, retention, and reversal, whereas lesions of the MS/VDB produce large and permanent impairments of certain types of conditiona l learning, Similar impairments produced by scopolamine in monkeys and additive effects of lesions of the NBM or MS/VDB with scopolamine sug gest that scopolamine has these effects by acting on the rising cholin ergic pathways rather than on other cholinergic systems in the brain. It is argued that the rising cholinergic projections sustain the funct ions of the target areas; in the case of the hippocampus in humans, th e function is usually regarded as being the analysis of information in a way that is pertinent to the formation of episodic memories and in the case of the neocortex, is the analysis of information in a manner that is relevant to the cognitive processing of on-going events and th e acquisition of semantic knowledge. (C) 1998 Elsevier Science Inc.