TESTING THE NMDA, LONG-TERM POTENTIATION, AND CHOLINERGIC HYPOTHESES OF SPATIAL-LEARNING

The problems and issues associated with the use of pharmacological ant agonists in studies on learning and memory are considered in a review of the role of N-methyl-D-aspartate (NMDA) receptors, NMDA receptor-me diated long-term potentiation (LTP), and muscarinic receptors in spati al learning in the water maze. The evidence indicates that neither NMD A nor muscarinic receptors, nor NMDA receptor-mediated LTP, are requir ed for spatial learning, although they might normally contribute to it . Detailed behavioral analyses have indicated that the water maze task is more complex than generally has been appreciated, and has a number of dissociable components. Naive rats trained under NMDA or muscarini c antagonism display sensorimotor disturbances that interfere with the ir ability to acquire the task. Rats made familiar with the general re quirements of the task can learn the location of a hidden platform rea dily under NMDA or muscarinic antagonism. The ability of a rat to acqu ire the water maze task depends on its ability to apply instinctive be haviors to performance of the task in an adaptive manner. The instinct ive behaviors undergo modification as the rat learns the general strat egies required in the task. The evidence suggests that at least some o f the plastic changes involved in acquiring the task occur in existing neural circuits situated in widespread areas of the brain, Including sensory and motor structures in the cortex and elsewhere, and are ther efore difficult to distinguish from existing sensorimotor mechanisms. More generally, the findings indicate the difficulty of inferring the occurrence or nonoccurrence of learning from behavior, and the difficu lty of causally linking the action of particular receptor populations with the formation of specific memories. (C) 1998 Elsevier Science Ltd . All rights reserved.